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1. Impact of Human Immunodeficiency Virus Type 1 Minority Variants on the Virus Response to a Rilpivirine-Based First-line Regimen

Author: Raymond, Stéphanie, Nicot, Florence, Pallier, Coralie, Bellecave, Pantxika, Maillard, Anne, Trabaud, Mary Anne, Morand-Joubert, Laurence, Rodallec, Audrey, Amiel, Corinne, Mourez, Thomas, Bocket, Laurence, Beby-Defaux, Agnès, Bouvier-Alias, Magali, Lambert-Niclot, Sidonie, Charpentier, Charlotte, Malve, Brice, Mirand, Audrey, Dina, Julia, Le Guillou-Guillemette, Hélène, Marque-Juillet, Stéphanie, Signori-Schmuck, Anne, Barin, Francis, Si-Mohamed, Ali, Fenoel, Véronique Avettand, Roussel, Catherine, Calvez, Vincent, Saune, Karine, Marcelin, Anne Geneviève, Rodriguez, Christophe, Descamps, Diane, Izopet, Jacques, Lagier, E, Roussel, C, Le Guillou-Guillemette, H, Alloui, C, Bettinger, D, Pallier, C, Fleury, H, Reigadas, S, Bellecave, P, Recordon-Pinson, P, Payan, C, Vallet, S, Vabret, A, Dina, J, Henquell, C, Mirand, A, Bouvier-Alias, M, de Rougemont, A, Dos Santos, G, Morand, P, Signori-Schmuck, A, Bocket, L, Rogez, S, Andre, P, Tardy, JC, Trabaud, MA, Tamalet, C, Delamare, C, Montes, B, Schvoerer, E, Ferré, V, André-Garnier, E, Cottalorda, J, Guinard, J, Guiguon, A, Descamps, D, Brun-Vézinet, F, Charpentier, C, Visseaux, B, Peytavin, G, Krivine, A, Si-Mohamed, A, Avettand-Fenoel, V, Marcelin, AG, Calvez, V, Lambert-Niclot, S, Soulié, C, Wirden, M, Morand-Joubert, L, Delaugerre, C, Chaix, ML, Amiel, C, Schneider, V, Giraudeau, G, Defaux, A Beby-, Brodard, V, Maillard, A, Plantier, JC, Chaplain, C, Bourlet, T, Fafi-Kremer, S, Stoll-Keller, F, Schmitt, MP, Barth, H, Yerly, S, Poggi, C, Izopet, J, Raymond, S, and Barin, F
Subjects: Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Immunology, Sexually Transmitted Infections, Clinical Research, Infectious Diseases, Genetics, Minority Health, Antimicrobial Resistance, HIV/AIDS, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Adult, Drug Resistance, Viral, Female, Genetic Variation, HIV Infections, HIV-1, Humans, Male, Mutation, Rilpivirine, Viral Load, minority resistant variants, rilpivirine, first-line antiretroviral therapy, ultra-deep sequencing, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group, Biological Sciences, Medical and Health Sciences, Microbiology, Clinical sciences
Abstract: BackgroundMinority resistant variants of human immunodeficiency virus type 1 (HIV-1) could influence the virological response to treatment based on nonnucleoside reverse transcriptase inhibitors (NNRTIs). Data on minority rilpivirine-resistant variants are scarce. This study used next-generation sequencing (NGS) to identify patients harboring minority resistant variants to nucleos(t)ide reverse transcriptase inhibitors and NNRTIs and to assess their influence on the virological response (VR).MethodsAll the subjects, 541 HIV-1-infected patients started a first-line regimen containing rilpivirine. VR was defined as a HIV-1 RNA load 20% in 29% of samples. We identified 43 (8.8%) and 36 (7.4%) patients who harbored rilpivirine-resistant variants with a 1% sensitivity threshold according to the French National Agency for Research on AIDS and Viral Hepatitis and Stanford algorithms, respectively. The VR was 96.9% at month 12. Detection of minority rilpivirine resistant variants was not associated with virological failure (VF). Multivariate analysis indicated that VF at month 12 was associated with a CD4 count
Published: 2018

2. Impact of the mutational load on the virological response to a first-line rilpivirine-based regimen.

Author: Dimeglio, Chloé, Raymond, Stéphanie, Nicot, Florence, Jeanne, Nicolas, Carcenac, Romain, Lefebvre, Caroline, Izopet, Jacques, Roussel, C, Guillou-Guillemette, H Le, Alloui, C, Bettinger, D, Pallier, C, Fleury, H, Bellecave, P, Recordon-Pinson, P, Payan, C, Vallet, S, Vabret, A, Dina, J, Henquell, C, Mirand, A, Bouvier-Alias, M, de Rougemont, A, Si-Mohammed, A, Santos, G Dos, Morand, P, Signori-Schmuck, A, Bocket, L, Rogez, S, Andre, P, Tardy, JC, Trabaud, MA, Tamalet, C, Delamare, C, Montes, B, Schvoerer, E, Jeulin, H, Ferré, V, Rodallec, A, Guen, L Le, Cottalorda, J, Guinard, J, Guiguon, A, Descamps, D, Charpentier, C, Visseaux, B, Peytavin, G, Krivine, A, Bouviers-Alias, M, Avettand-Fenoel, V, Marcelin, AG, Calvez, V, Soulié, C, Wirden, M, Morand-Joubert, L, Lambert-Niclot, S, Fofana, D, Delaugerre, C, Chaix, ML, Mahjoub, N, Amiel, C, Schneider, V, Giraudeau, G, Beby-Defaux, A, Brodard, V, Maillard, A, Plantier, JC, Mourez, T, Leoz, M, Chaplain, C, Bourlet, T, Fafi-Kremer, S, Stoll-Keller, F, Schmitt, MP, Barth, H, Yerly, S, Poggi, C, Izopet, J, Raymond, S, Barin, F, Chaillon, A, Marque-Juillet, S, Roque-Afonso, AM, Haïm-Boukobza, S, Flandre, P, Grudé, M, Assoumou, L, and Costagliola, D
Subjects: Clinical Research, Genetics, HIV/AIDS, Infectious Diseases, Infection, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, Female, Genome, Viral, Genotype, HIV Infections, HIV-1, High-Throughput Nucleotide Sequencing, Humans, Male, Mutation, Rilpivirine, Treatment Outcome, Viral Load, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group, Microbiology, Medical Microbiology, Pharmacology and Pharmaceutical Sciences
Abstract: ObjectivesTo determine how the load of rilpivirine-resistant variants (mutational load) influences the virological response (VR) of HIV-1-infected patients to a rilpivirine-based first-line regimen.Patients and methodsFour hundred and eighty-nine patients infected with HIV-1 whose reverse transcriptase gene had been successfully resistance genotyped using next-generation sequencing were given a first-line regimen containing rilpivirine. Variables associated with the VR at 12 months were identified using a logistic model. The results were used to build a multivariate model for each mutational load threshold and the R2 variations were analysed to identify the mutational load threshold that best predicted the VR.ResultsThe mutational load at baseline was the only variable linked to the VR at 12 months (P 1700 copies/mL and to 50% when the mutational load was > 9000 copies/mL. The threshold of 9000 copies/mL was associated with the VR at 12 months with an OR of 36.7 (95% CI 4.7-285.1). The threshold of 1700 copies/mL was associated with the VR at 12 months with an OR of 7.2 (95% CI 1.4-36.8).ConclusionsThere is quantifiable evidence that determining a mutational load threshold can be used to identify those patients on a first-line regimen containing rilpivirine who are at risk of virological failure. The clinical management of HIV-infected patients can be improved by evaluating the frequency of mutant variants at a threshold of
Published: 2019

3. Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients

Author: Fourati, Slim, Charpentier, Charlotte, Amiel, Corinne, Morand-Joubert, Laurence, Reigadas, Sandrine, Trabaud, Mary-Anne, Delaugerre, Constance, Nicot, Florence, Rodallec, Audrey, Maillard, Anne, Mirand, Audrey, Jeulin, Hélène, Montès, Brigitte, Barin, Francis, Bettinger, Dominique, Le Guillou-Guillemette, Hélène, Vallet, Sophie, Signori-Schmuck, Anne, Descamps, Diane, Calvez, Vincent, Flandre, Philippe, Marcelin, Anne-Genevieve, Lagier, E, Roussel, C, Le Guillou, H, Alloui, C, Bettinger, D, Pallier, C, Fleury, H, Reigadas, S, Bellecave, P, Recordon-Pinson, P, Payan, C, Vallet, S, Vabret, A, Henquell, C, Mirand, A, Bouvier-Alias, M, de Rougemont, A, Dos Santos, G, Morand, P, Signori-Schmuck, A, Bocket, L, Rogez, S, Andre, P, Tardy, JC, Trabaud, MA, Tamalet, C, Delamare, C, Montes, B, Schvoerer, E, Ferre, V, André-Garnier, E, Cottalorda, J, Guinard, J, Guiguon, A, Descamps, D, Brun-Vézinet, F, Charpentier, C, Visseaux, B, Peytavin, G, Krivine, A, Si-Mohamed, A, Avettand-Fenoel, V, Marcelin, AG, Calvez, V, Lambert-Niclot, S, Soulié, C, Wirden, M, Morand-Joubert, L, Delaugerre, C, Chaix, ML, Amiel, C, Schneider, V, Giraudeau, G, Brodard, V, Maillard, A, Plantier, JC, Chaplain, C, Bourlet, T, Fafi-Kremer, S, Stoll-Keller, F, Schmitt, MP, Barth, H, Yerly, S, Poggi, C, Izopet, J, Raymond, S, Barin, F, Chaillon, A, Marque-Juillet, S, Roque-Afonso, AM, Haïm-Boukobza, S, Flandre, P, Grudé, M, Assoumou, L, Costagliola, D, Allegre, T, Schmit, JL, and Chennebault, JM
Subjects: Medical Microbiology, Biomedical and Clinical Sciences, Infectious Diseases, Genetics, Aetiology, 2.1 Biological and endogenous factors, Infection, Adult, Anti-HIV Agents, Drug Resistance, Viral, Female, France, HIV Infections, HIV Integrase, HIV Protease, HIV Reverse Transcriptase, HIV-1, Heterocyclic Compounds, 3-Ring, Humans, Male, Middle Aged, Mutant Proteins, Oxazines, Piperazines, Pyridones, Quinolones, Raltegravir Potassium, Sequence Analysis, DNA, integrase, inhibitors, mutations, patterns, ANRS AC11 Resistance Study Group, Microbiology, Pharmacology and Pharmaceutical Sciences, Clinical sciences, Pharmacology and pharmaceutical sciences
Abstract: ObjectivesThe objectives of this study were to determine the prevalence and patterns of resistance to integrase strand transfer inhibitors (INSTIs) in patients experiencing virological failure on raltegravir-based ART and the impact on susceptibility to INSTIs (raltegravir, elvitegravir and dolutegravir).Patients and methodsData were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23).ResultsAmong the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log10 copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure (P
Published: 2015

4. Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Author: Soulie, C, Descamps, D, Grude, M, Schneider, V, Trabaud, M-A, Morand-Joubert, L, Delaugerre, C, Montes, B, Barin, F, Ferre, V, Raymond, S, Jeulin, H, Alloui, C, Yerly, S, Pallier, C, Reigadas, S, Signori-Schmuck, A, Guigon, A, Fafi-Kremer, S, Haim-Boukobza, S, Mirand, A, Maillard, A, Vallet, S, Roussel, C, Assoumou, L, Calvez, V, Flandre, P, Marcelin, A-G, Lagier, E, Le Guillou, H, Bettinger, D, Fleury, H, Bellecave, P, Recordon-Pinson, P, Payan, C, Vabret, A, Henquell, C, Bouvier-Alias, M, de Rougemont, A, Dos Santos, G, Morand, P, Bocket, L, Rogez, S, Andre, P, Tardy, JC, Trabaud, MA, Tamalet, C, Delamare, C, Schvoerer, E, Andre-Garnier, E, Cottalorda, J, Guinard, J, Guiguon, A, Brun-Vezinet, F, Charpentier, C, Visseaux, B, Peytavin, G, Krivine, A, Si-Mohamed, A, Avettand-Fenoel, V, Marcelin, AG, Lambert-Niclot, S, Wirden, M, Chaix, ML, Amiel, C, Giraudeau, G, Brodard, V, Plantier, JC, Chaplain, C, Bourlet, T, Stoll-Keller, F, Schmitt, MP, Barth, H, Poggi, C, Izopet, J, Chaillon, A, Marque-Juillet, S, and Roque-Afonso, AM
Subjects: Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, HIV/AIDS, Infectious Diseases, Antimicrobial Resistance, Genetics, Clinical Research, Neurosciences, Infection, Adult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, Female, Genotype, HIV Infections, HIV-1, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Mutation, Nervous System Diseases, Viral Load, ANRS Resistance AC11 Group, ARV, CSF, HIV, resistance, Microbiology, Pharmacology and Pharmaceutical Sciences, Clinical sciences, Pharmacology and pharmaceutical sciences
Abstract: OBJECTIVES: The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. METHODS: Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. RESULTS: On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P=0.0455) and T215Y (P=0.0455). CONCLUSIONS: In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performed.
Published: 2015

5. No increased risk of Kaposi sarcoma relapse in patients with controlled HIV‐1 infection after switching protease inhibitor‐based antiretroviral therapy

Author: Lajaunie, Rébecca, Cuzin, Lise, Palich, Romain, Makinson, Alain, Bani-Sadr, Firouzé, Duvivier, Claudine, Arvieux, Cedric, Rey, David, Poizot-Martin, Isabelle, Delpierre, Cyril, Delobel, Pierre, Martin-Blondel, Guillaume, Chirouze, C., Drobacheff-Thiébaut, C., Foltzer, A., Bouiller, K., Hustache- Mathieu, L., Lepiller, Q., Bozon, F., Babre, O, Brunel, As., Muret, P., Chevalier, E., Jacomet, C., Laurichesse, H., Lesens, O., Vidal, M., Mrozek, N., Aumeran, C., Baud, O., Corbin, V., Goncalvez, E., Mirand, A, Brebion, A, Henquell, C, Lamaury, I., Fabre, I., Curlier, E., Ouissa, R., Herrmann-Storck, C., Tressieres, B., Receveur, Mc., Boulard, F., Daniel, C., Clavel, C., Roger, Pm., Markowicz, S., Chellum Rungen, N., Merrien, D., Perré, P., Guimard, T., Bollangier, O., Leautez, S., Morrier, M., Laine, L., Boucher, D., Point, P., Cotte, L., Ader, F., Becker, A., Boibieux, A., Brochier, C., Brunel-Dalmas, F., Cannesson, O., Chiarello, P., Chidiac, C., Degroodt, S., Ferry, T., Godinot, M., Livrozet, J.M., Makhloufi, D., Miailhes, P., Perpoint, T., Perry, M., Pouderoux, C., Roux, S., Triffault-Fillit, C., Valour, F., Charre, C., Icard, V., Tardy, J.C., Trabaud, M.A., Ravaux, I., Ménard, A., Belkhir, Ay., Colson, P., Dhiver, C., Madrid, A., Martin-Degioanni, M., Meddeb, L., Mokhtari, M., Motte, A., Raoux, A., Toméi, C., Tissot-Dupont, H., Poizot-Martin, I., Brégigeon, S., Zaegel-Faucher, O., Obry-Roguet, V., Laroche, H, Orticoni, M., Soavi, M.J., Ressiot, E., Ducassou, M.J., Jaquet, I., Galie, S., Colson, H., Ritleng, A.S., Ivanova, A., Debreux, C., Lions, C., Rojas-Rojas, T, Cabié, A., Abel, S., Bavay, J., Bigeard, B., Cabras, O., Cuzin, L., Dupin de Majoubert, R., Fagour, L., Guitteaud, K., Marquise, A., Najioullah, F., Pierre-François, S., Pasquier, J., Richard, P., Rome, K., Turmel, Jm, Varache, C., Atoui, N., Bistoquet, M., Delaporte, E, Le Moing, V., Makinson, A., Meftah, N., Merle de Boever, C., Montes, B., Montoya Ferrer, A., Tuaillon, E., Reynes, J., Lefèvre, B., Jeanmaire, E., Hénard, S., Frentiu, E., Charmillon, A., Legoff, A., Tissot, N., André, M., Boyer, L., Bouillon, Mp., Delestan, M., Goehringer, F., Bevilacqua, S., Rabaud, C., May, T., Raffi, F., Allavena, C., Aubry, O., Billaud, E., Biron, C., Bonnet, B., Bouchez, S., Boutoille, D., Brunet-Cartier, C., Deschanvres, C., Gaborit, B.J., Grégoire, A., Grégoire, M., Grossi, O., Guéry, R., Jovelin, T., Lefebvre, M., Le Turnier, P., Lecomte, R., Morineau, P., Reliquet, V., Sécher, S., Cavellec, M., Paredes, E., Soria, A., Ferré, V., André-Garnier, E., Rodallec, A., Pugliese, P., Breaud, S., Ceppi, C., Chirio, D., Cua, E., Dellamonica, P., Demonchy, E., de Monte, A., Durant, J., Etienne, C., Ferrando, S., Garraffo, R., Michelangeli, C., Mondain, V., Naqvi, A., Oran, N., Perbost, I., Carles, M., Klotz, C., Maka, A., Pradier, C., Prouvost-Keller, B., Risso, K., Rio, V., Rosenthal, E., Touitou, I., Wehrlen-Pugliese, S., Zouzou, G., Hocqueloux, L., Prazuck, T., Gubavu, C., Sève, A., Giaché, S., Rzepecki, V., Colin, M., Boulard, C., Thomas, G., Cheret, A., Goujard, C., Quertainmont, Y., Teicher, E., Lerolle, N., Jaureguiberry, S., Colarino, R., Deradji, O., Castro, A., Barrail-Tran, A., Yazdanpanah, Y., Landman, R., Joly, V., Ghosn, J., Rioux, C., Lariven, S., Gervais, A., Lescure, Fx., Matheron, S., Louni, F., Julia, Z., Le Gac, S., Charpentier, C., Descamps, D., Peytavin, G., Duvivier, C., Aguilar, C., Alby-Laurent, F., Amazzough, K., Benabdelmoumen, G., Bossi, P., Cessot, G., Charlier, C., Consigny, P.H., Jidar, K., Lafont, E., Lanternier, F., Leporrier, J., Lortholary, O., Louisin, C., Lourenco, J., Parize, P., Pilmis, B., Rouzaud, C., Touam, F., Valantin, Ma., Tubiana, R., Agher, R., Seang, Sophie, Schneider, L., Palich, R., Blanc, C., Katlama, C., Bani-Sadr, F., Berger, Jl., N’guyen, Y., Lambert, D., Kmiec, I., Hentzien, M., Brunet, A., Romaru, J., Marty, H., Brodard, V., Arvieux, C., Tattevin, P., Revest, M., Souala, F., Baldeyrou, M., Patrat-Delon, S., Chapplain, J.M., Benezit, F., Dupont, M., Poinot, M., Maillard, A., Pronier, C., Lemaitre, F., Morlat, C., Poisson-Vannier, M., Sinteff, Jp., Gagneux-Brunon, A., Botelho-Nevers, E., Frésard, A., Ronat, V., Lucht, F., Rey, D., Fischer, P., Partisani, M., Cheneau, C., Priester, M., Batard, Ml., Mélounou, C, Bernard-Henry, C., de Mautort, E., Fafi-Kremer, S., Delobel, P., Alvarez, M., Biezunski, N., Debard, A., Delpierre, C., Gaube, G., Lansalot, P., Lelièvre, L., Marcel, M., Martin-Blondel, G., Piffaut, M., Porte, L., Saune, K., Robineau, O., Ajana, F., Aïssi, E., Alcaraz, I., Alidjinou, E., Baclet, V., Bocket, L., Boucher, A., Digumber, M., Huleux, T., Lafon-Desmurs, B., Meybeck, A., Pradier, M., Tetart, M., Thill, P., Viget, N., Valette, M., Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU de la Martinique [Fort de France], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Reims (CHU Reims), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), CHU Pontchaillou [Rennes], CHU Strasbourg, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse III Paul Sabatier - Faculté de médecine Purpan (UTPS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), And The Dat’AIDS study group: C Chirouze, C Drobacheff-Thiébaut, A Foltzer, K Bouiller, L Hustache-Mathieu, Q Lepiller, F Bozon, O Babre, A S Brunel, P Muret, E Chevalier, C Jacomet, H Laurichesse, O Lesens, M Vidal, N Mrozek, C Aumeran, O Baud, V Corbin, E Goncalvez, A Mirand, A Brebion, C Henquell, I Lamaury, I Fabre, E Curlier, R Ouissa, C Herrmann-Storck, B Tressieres, M C Receveur, F Boulard, C Daniel, C Clavel, P M Roger, S Markowicz, N Chellum Rungen, D Merrien, P Perré, T Guimard, O Bollangier, S Leautez, M Morrier, L Laine, D Boucher, P Point, L Cotte, F Ader, A Becker, A Boibieux, C Brochier, F Brunel-Dalmas, O Cannesson, P Chiarello, C Chidiac, S Degroodt, T Ferry, M Godinot, J M Livrozet, D Makhloufi, P Miailhes, T Perpoint, M Perry, C Pouderoux, S Roux, C Triffault-Fillit, F Valour, C Charre, V Icard, J C Tardy, M A Trabaud, I Ravaux, A Ménard, A Y Belkhir, P Colson, C Dhiver, A Madrid, M Martin-Degioanni, L Meddeb, M Mokhtari, A Motte, A Raoux, C Toméi, H Tissot-Dupont, I Poizot-Martin, S Brégigeon, O Zaegel-Faucher, V Obry-Roguet, H Laroche, M Orticoni, M J Soavi, E Ressiot, M J Ducassou, I Jaquet, S Galie, H Colson, A S Ritleng, A Ivanova, C Debreux, C Lions, T Rojas-Rojas, A Cabié, S Abel, J Bavay, B Bigeard, O Cabras, L Cuzin, R Dupin de Majoubert, L Fagour, K Guitteaud, A Marquise, F Najioullah, S Pierre-François, J Pasquier, P Richard, K Rome, J M Turmel, C Varache, N Atoui, M Bistoquet, E Delaporte, V Le Moing, A Makinson, N Meftah, C Merle de Boever, B Montes, A Montoya Ferrer, E Tuaillon, J Reynes, B Lefèvre, E Jeanmaire, S Hénard, E Frentiu, A Charmillon, A Legoff, N Tissot, M André, L Boyer, M P Bouillon, M Delestan, F Goehringer, S Bevilacqua, C Rabaud, T May, F Raffi, C Allavena, O Aubry, E Billaud, C Biron, B Bonnet, S Bouchez, D Boutoille, C Brunet-Cartier, C Deschanvres, B J Gaborit, A Grégoire, M Grégoire, O Grossi, R Guéry, T Jovelin, M Lefebvre, P Le Turnier, R Lecomte, P Morineau, V Reliquet, S Sécher, M Cavellec, E Paredes, A Soria, V Ferré, E André-Garnier, A Rodallec, P Pugliese, S Breaud, C Ceppi, D Chirio, E Cua, P Dellamonica, E Demonchy, A De Monte, J Durant, C Etienne, S Ferrando, R Garraffo, C Michelangeli, V Mondain, A Naqvi, N Oran, I Perbost, M Carles, C Klotz, A Maka, C Pradier, B Prouvost-Keller, K Risso, V Rio, E Rosenthal, I Touitou, S Wehrlen-Pugliese, G Zouzou, L Hocqueloux, T Prazuck, C Gubavu, A Sève, S Giaché, V Rzepecki, M Colin, C Boulard, G Thomas, A Cheret, C Goujard, Y Quertainmont, E Teicher, N Lerolle, S Jaureguiberry, R Colarino, O Deradji, A Castro, A Barrail-Tran, Y Yazdanpanah, R Landman, V Joly, J Ghosn, C Rioux, S Lariven, A Gervais, F X Lescure, S Matheron, F Louni, Z Julia, S Le Gac, C Charpentier, D Descamps, G Peytavin, C Duvivier, C Aguilar, F Alby-Laurent, K Amazzough, G Benabdelmoumen, P Bossi, G Cessot, C Charlier, P H Consigny, K Jidar, E Lafont, F Lanternier, J Leporrier, O Lortholary, C Louisin, J Lourenco, P Parize, B Pilmis, C Rouzaud, F Touam, M A Valantin, R Tubiana, R Agher, S Seang, L Schneider, R Palich, C Blanc, C Katlama, F Bani-Sadr, J L Berger, Y N'Guyen, D Lambert, I Kmiec, M Hentzien, A Brunet, J Romaru, H Marty, V Brodard, C Arvieux, P Tattevin, M Revest, F Souala, M Baldeyrou, S Patrat-Delon, J M Chapplain, F Benezit, M Dupont, M Poinot, A Maillard, C Pronier, F Lemaitre, C Morlat, M Poisson-Vannier, T Jovelin, J P Sinteff, A Gagneux-Brunon, E Botelho-Nevers, A Frésard, V Ronat, F Lucht, D Rey, P Fischer, M Partisani, C Cheneau, M Priester, M L Batard, C Mélounou, C Bernard-Henry, E de Mautort, S Fafi-Kremer, P Delobel, M Alvarez, N Biezunski, A Debard, C Delpierre, G Gaube, P Lansalot, L Lelièvre, M Marcel, G Martin-Blondel, M Piffaut, L Porte, K Saune, O Robineau, F Ajana, E Aïssi, I Alcaraz, E Alidjinou, V Baclet, L Bocket, A Boucher, M Digumber, T Huleux, B Lafon-Desmurs, A Meybeck, M Pradier, M Tetart, P Thill, N Viget, M Valette, Malbec, Odile, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Rennes (CHU Rennes), Laboratoire de Physique des Lasers (LPL), Université Paris 13 (UP13)-Centre National de la Recherche Scientifique (CNRS)-Université Sorbonne Paris Nord, Service d'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Institut des sciences de la santé publique [Marseille] (ISSPAM), European Infective Endocarditis Registry (Euro-Endo), EMERGEN consortium, Stratégies thérapeutiques contre l'infection VIH et les maladies virales associées [iPLesp] (THERAVIR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Laboratoire Microorganismes : Génome et Environnement (LMGE), and Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)
Subjects: medicine.medical_specialty, MESH: CD4 Lymphocyte Count, [SDV]Life Sciences [q-bio], antiretroviral therapy, Human immunodeficiency virus (HIV), protease inhibitors, HIV Infections, medicine.disease_cause, MESH: HIV-1, Acquired immunodeficiency syndrome (AIDS), MESH: Neoplasm Recurrence, Local / complications, Internal medicine, medicine, Humans, HHV8, MESH: HIV Infections* / complications, MESH: Protease Inhibitors / adverse effects, Pharmacology (medical), Protease inhibitor (pharmacology), Sarcoma, Kaposi, Retrospective Studies, MESH: Humans, business.industry, Health Policy, Kaposi sarcoma, MESH: Retrospective Studies, Viral Load, MESH: HIV Infections* / drug therapy, medicine.disease, Antiretroviral therapy, switch, CD4 Lymphocyte Count, AIDS, [SDV] Life Sciences [q-bio], Regimen, Infectious Diseases, Increased risk, MESH: Sarcoma, Kaposi* / drug therapy, HIV-1, Sarcoma, Neoplasm Recurrence, Local, business, MESH: Viral Load, Viral load
Abstract: International audience; Objectives: Our aim was to assess if switching from a protease inhibitors (PI)-based regimen to a PI-free one is associated with an increased risk of Kaposi Sarcoma (KS) relapse among patients living with HIV (PLHIV) with history of KS and controlled HIV replication.Methods: In a retrospective analysis of the prospectively collected Dat'AIDS database we selected patients who both had a past KS history and a HIV-1 viral load below 200 copies/mL while being PI-treated. We searched for KS relapses while persistent virological success was maintained for at least 6 months, whether patients kept taking the PI, or switched to PI-free regimen.Results: Among the 216 patients with past KS event and a history of HIV-1 infection efficiently treated by a PI-based regimen, 148 patients (68.5%) later switched to a PI-sparing regimen. Their baseline characteristics were not different from non-switching patients. We described 7 cases of relapse (3.2% of the 216 patients). Five cases of relapse occurred in switching patients (3.4%). The remaining two relapses occurred in PI-treated patients (2.9%). At KS relapse, CD4 cell count was 459 cells/μL (range 225-560) for switching patients, compared with 362 and 136 cells/μL for the other two patients.Conclusions: In this large cohort of PLHIV with a history of KS and ART-controlled HIV replication, KS relapses were described in 3.2% of the patients, and were not more frequent when a PI-containing ART regimen has been switched to a PI-free regimen. Our results do not support a specific effect of PI on KS.
Published: 2022
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6. Surveillance of HIV-1 primary infections in France from 2014 to 2016: toward stable resistance, but higher diversity, clustering and virulence?

Author: Visseaux, Benoit, Assoumou, Lambert, Grude, Maxime, Carles, Marie-Josée, Meyer, Laurence, Roussel, Catherine, Le Guillou-Guillemette, H., Ducancelle, A., Courdavault, L, Alloui, C, Honore, P, Lepiller, Q., Bettinger, D., Bellecave, P., Pinson-Recordon, P, Tumiotto, Camille, Vallet, Sophie, Payan, C., Duthe, J, Leroux, M., Dina, Julia, Vabret, A., Mirand, A., Henquell, C., Bouvier-Alias, Magali, Simohamed, A, dos Santos, G, yerly, S, Gaille, C, Caveng, W, Chapalay, S, Calmy, A., Signori-Schmuck, Anne, Morand, Patrice, Pallier, Coralie, Raho-Moussa, M, Mole, M, Dulucq, M-J, Bocket, Laurence, Alidjinou, K, Ranger-Rogez, S, Trabaud, Mary-Anne, Icard, V, Tardy, J., Tamalet, C., Delamare, C, Montes, Brigitte, Schvoerer, E., Fenaux, H., Rodallec, A., André-Garnier, E., Ferre, Virginie, de Monte, Anne, Guigon, A., Guinard, J., Descamps, Diane, Charpentier, C., Peytavin, G., Tremaux, P, Avettand-Fenoel, V., Soulie, C., Malet, I., Wirden, Marc, Marcelin, A, Calvez, V., Flandre, P., Costagliola, D, Morand-Joubert, Laurence, Lambert-Niclot, S., Fofana, D, Boukli, N., Delaugerre, C., Chaix, Marie-Laure, Mahjoub, Nadia, Amiel, Corinne, Giraudeau, G, Beby-Defaux, A., Plainchamp, D, Maillard, Anne, Alessandri-Gradt, E, Leoz, M, Plantier, Jean-Christophe, Gantner, P, Delagreverie, H, Fafi-Kremer, Samira, Fischer, P, Raymond, Stéphanie, Izopet, Jacques, Chiabrando, J, Stefic, Karl, Barin, F., Fajole, G, Burgault, O, Marque-Juillet, S, Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), virology, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de recherche sur l'hétéroepitaxie et ses applications (CRHEA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Clermont-Ferrand, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Geneva University Hospital (HUG), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de virologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôtel-Dieu de Nantes, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Pharmacie de l'Hôpital Bichat, Centre de Recherches Pétrographiques et Géochimiques (CRPG), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Service de microbiologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Unité de Rétrovirologie, Hôpital Pontchaillou, Normandie Université (NU), Laboratoire de Virologie, CHU Strasbourg, Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Centre national de référence du VIH INSERM U966, Université de Tours (UT), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Besançon, Université de Franche-Comté (UFC), Université Grenoble Alpes (UGA), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU AMU), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université de Tours, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Male, Etravirine, HIV Infections, Men who have sex with men, Sexual and Gender Minorities, chemistry.chemical_compound, Pre-exposure prophylaxis, 0302 clinical medicine, Pharmacology (medical), 030212 general & internal medicine, Phylogeny, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, education.field_of_study, Virulence, biology, [SDE.IE]Environmental Sciences/Environmental Engineering, Middle Aged, Viral Load, 3. Good health, Integrase, Infectious Diseases, Rilpivirine, Epidemiological Monitoring, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, France, Viral load, medicine.drug, Adult, Microbiology (medical), Genotype, Anti-HIV Agents, [SDE.MCG]Environmental Sciences/Global Changes, Population, Evolution, Molecular, 03 medical and health sciences, Drug Resistance, Viral, medicine, Humans, education, Pharmacology, 030306 microbiology, Genetic Variation, Sequence Analysis, DNA, [SDE.ES]Environmental Sciences/Environmental and Society, Virology, chemistry, Mutation, HIV-1, biology.protein, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract: ObjectivesPatients with primary HIV-1 infection (PHI) are a particular population, giving important insight about ongoing evolution of transmitted drug resistance-associated mutation (TDRAM) prevalence, HIV diversity and clustering patterns. We describe these evolutions of PHI patients diagnosed in France from 2014 to 2016.MethodsA total of 1121 PHI patients were included. TDRAMs were characterized using the 2009 Stanford list and the French ANRS algorithm. Viral subtypes and recent transmission clusters (RTCs) were also determined.ResultsPatients were mainly MSM (70%) living in the Paris area (42%). TDRAMs were identified among 10.8% of patients and rose to 18.6% when including etravirine and rilpivirine TDRAMs. Prevalences of PI-, NRTI-, first-generation NNRTI-, second-generation NNRTI- and integrase inhibitor-associated TDRAMs were 2.9%, 5.0%, 4.0%, 9.4% and 5.4%, respectively. In a multivariable analysis, age >40 years and non-R5 tropic viruses were associated with a >2-fold increased risk of TDRAMs. Regarding HIV diversity, subtype B and CRF02_AG (where CRF stands for circulating recombinant form) were the two main lineages (56% and 20%, respectively). CRF02_AG was associated with higher viral load than subtype B (5.83 versus 5.40 log10 copies/mL, P = 0.004). We identified 138 RTCs ranging from 2 to 14 patients and including overall 41% from the global population. Patients in RTCs were younger, more frequently born in France and more frequently MSM.ConclusionsSince 2007, the proportion of TDRAMs has been stable among French PHI patients. Non-B lineages are increasing and may be associated with more virulent CRF02_AG strains. The presence of large RTCs highlights the need for real-time cluster identification to trigger specific prevention action to achieve better control of the epidemic.
Published: 2019
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7. Resistance to integrase inhibitors: a national study in HIV-1-infected treatment-naive and -experienced patients

Author: Constance Delaugerre, Virginie Ferré, Anne Maillard, Vincent Calvez, Audrey Mirand, Anne-Geneviève Marcelin, Corinne Amiel, Julia Dina, Coralie Pallier, Hélène Le Guillou-Guillemette, Stéphanie Raymond, D. B. Fofana, Thomas Mourez, Hélène Jeulin, Samira Fafi-Kremer, Brigitte Montes, Pantxika Bellecave, Sophie Vallet, Thuy Van Nguyen, Diane Descamps, Catherine Roussel, Maxime Grude, Mary-Anne Trabaud, Charlotte Charpentier, Laurence Bocket, Philippe Flandre, Laura Le Guen, Anne Signori-Schmuck, Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Toulouse [Toulouse], Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Simulation et Traitement de l'information pour l'Exploitation des systèmes de Production (EDF R&D STEP), EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Microbiologie Fondamentale et Pathogénicité (MFP), Service de virologie et unité de surveillance biologique [Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Clermont-Ferrand, CHU Lille, CHU Saint-Antoine [AP-HP], Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Saint Eloi (CHRU Montpellier), Service de Virologie [CHRU Nancy], CHU Strasbourg, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université de Caen Normandie (UNICAEN), Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Toulouse], CHU Saint-Eloi, Mzembaba, Sandy, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, 0301 basic medicine, MESH: Sequence Analysis, DNA, MESH: Treatment Failure, Aucun, Integrase inhibitor, HIV Infections, Drug resistance, MESH: HIV Seropositivity / drug therapy, MESH: Genotype, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, HIV Seropositivity, Pharmacology (medical), Treatment Failure, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Middle Aged, biology, Elvitegravir, Middle Aged, Viral Load, 3. Good health, Integrase, MESH: HIV-1 / genetics, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Dolutegravir, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Viral load, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, MESH: Mutation, Genotype, MESH: HIV Integrase Inhibitors / therapeutic use, 030106 microbiology, MESH: HIV Infections / drug therapy, MESH: Drug Resistance, Multiple, Viral / genetics, MESH: HIV-1 / drug effects, 03 medical and health sciences, Drug Resistance, Multiple, Viral, Internal medicine, medicine, Humans, HIV Integrase Inhibitors, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Pharmacology, MESH: Viral Load / drug effects, MESH: Humans, business.industry, MESH: Adult, Sequence Analysis, DNA, Raltegravir, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, Regimen, chemistry, Mutation, HIV-1, biology.protein, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, MESH: Female
Abstract: International audience; Objectives: To describe integrase strand transfer inhibitor (INSTI) resistance profiles and factors associated with resistance in antiretroviral-naive and -experienced patients failing an INSTI-based regimen in clinical practice.Methods: Data were collected from patients failing an INSTI-containing regimen in a multicentre French study between 2014 and 2017. Failure was defined as two consecutive plasma viral loads (VL) >50 copies/mL. Reverse transcriptase, protease and integrase coding regions were sequenced at baseline and failure. INSTI resistance-associated mutations (RAMs) included in the Agence Nationale de Recherches sur le SIDA genotypic algorithm were investigated.Results: Among the 674 patients, 359 were failing on raltegravir, 154 on elvitegravir and 161 on dolutegravir therapy. Overall, 90% were experienced patients and 389 (58%) patients showed no INSTI RAMs at failure. The strongest factors associated with emergence of at least one INSTI mutation were high VL at failure (OR = 1.2 per 1 log10 copies/mL increase) and low genotypic sensitivity score (GSS) (OR = 0.08 for GSS ≥3 versus GSS = 0-0.5). Patients failing dolutegravir also had significantly fewer INSTI RAMs at failure than patients failing raltegravir (OR = 0.57, P = 0.02) or elvitegravir (OR = 0.45, P = 0.005). Among the 68 patients failing a first-line regimen, 11/41 (27%) patients on raltegravir, 7/18 (39%) on elvitegravir and 0/9 on dolutegravir had viruses with emergent INSTI RAMs at failure.Conclusions: These results confirmed the robustness of dolutegravir regarding resistance selection in integrase in the case of virological failure in routine clinical care.
Published: 2019
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8. Stable prevalence of transmitted drug resistance mutations and increased circulation of non-B subtypes in antiretroviral-naive chronically HIV-infected patients in 2015/2016 in France

Author: Gilles Peytavin, Mary-Anne Trabaud, Anne Signori-Schmuck, Charlotte Charpentier, Marc Wirden, Cécile Henquell, Laurence Bocket, Catherine Delamare, Samira Fafi-Kremer, Jacques Izopet, Chakib Allaoui, Georges Dos Santos, A. Beby-Defaux, Benoit Visseaux, Virginie Ferré, Coralie Pallier, Diane Descamps, Stéphanie Marque-Juillet, Lambert Assoumou, Magali Bouvier-Alias, Sophie Vallet, Alexis de Rougemont, Hélène Le Guillou-Guillemette, Vincent Calvez, Stéphanie Raymond, Corinne Amiel, Honorine Fenaux, Anne De Monte, Francis Barin, Anne Krivine, Véronique Avettand-Fenoel, Annick Allardet-Servent, Jean-Christophe Plantier, Rachid Ait-Namane, Laurence Morand-Joubert, Marie-Laure Chaix, Camille Tumiotto, Maxime Grude, Anne Maillard, Laurence Courdavault, Brigitte Montes, Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Hôpital Avicenne [AP-HP], CHU Clermont-Ferrand, Service de Virologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU de la Martinique [Fort de France], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Victor Dupouy, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Sorbonne Paris Cité (USPC), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Laboratoire de Virologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Caen Normandie (UNICAEN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Mzembaba, Sandy, Epidémiologie, Systèmes d'Information, Modélisation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Virologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Paul Brousse, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Virologie Médicale et Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Laboratoire de Virologie-Immunologie [Fort de France, Martinique] (EA 4537), Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], CHU Henri Mondor, Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Sorbonne Université (SU), Service de virologie et unité de surveillance biologique [Bordeaux], CHU Strasbourg, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier Argenteuil (CH Argenteuil), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Paris Descartes, Sorbonne Paris Cité, Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Normandie Université (NU)-Normandie Université (NU), Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), and ANRS – France REcherche Nord&Sud Sida-hiv Hépatites
Subjects: 0301 basic medicine, Male, MESH: CD4 Lymphocyte Count, [SDV]Life Sciences [q-bio], Integrase inhibitor, hiv, HIV Infections, Drug resistance, MESH: HIV-1 / genetics, MESH: Genotype, MESH: HIV Infections / epidemiology, 0302 clinical medicine, Genotype, Blood plasma, HIV Seropositivity, rna-directed dna polymerase, Prevalence, rna, Pharmacology (medical), 030212 general & internal medicine, MESH: Chronic Disease / epidemiology, ComputingMilieux_MISCELLANEOUS, cd4 count determination procedure, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, anti-retroviral agents, MESH: France / epidemiology, Antiinfective agent, MESH: Middle Aged, Incidence (epidemiology), Middle Aged, MESH: Drug Resistance, Viral / genetics, 3. Good health, endopeptidases, [SDV] Life Sciences [q-bio], integrase inhibitors, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, MESH: RNA, Viral / blood, Female, France, MESH: HIV Seropositivity / epidemiology, Microbiology (medical), Adult, medicine.medical_specialty, peptide hydrolases, MESH: Mutation, Anti-HIV Agents, 030106 microbiology, MESH: HIV Infections / drug therapy, MESH: HIV-1 / classification, MESH: HIV-1 / drug effects, Virus, MESH: HIV Infections / transmission, 03 medical and health sciences, Pharmacotherapy, Internal medicine, Drug Resistance, Viral, medicine, Humans, viruses, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, plasma, safe sex, MESH: Prevalence, Pharmacology, drug resistance, MESH: Humans, business.industry, MESH: Adult, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, CD4 Lymphocyte Count, MESH: Anti-HIV Agents / therapeutic use, Chronic Disease, Mutation, HIV-1, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, MESH: Female
Abstract: International audience; Objectives: We estimated the prevalence of transmitted-drug-resistance-associated mutations (TDRAMs) in antiretroviral-naive chronically HIV-1-infected patients.Patients and methods: TDRAMs were sought in samples from 660 diagnosed HIV-1-infected individuals in 2015/2016 in 33 HIV clinical centres. Weighted analyses, considering the number of patients followed in each centre, were used to derive representative estimates of the percentage of individuals with TDRAMs. Results were compared with those of the 2010/2011 survey (n = 661) using the same methodology.Results: At inclusion, median CD4 cell counts and plasma HIV-1 RNA were 394 and 350/mm3 (P = 0.056) and 4.6 and 4.6 log10 copies/mL (P = 0.360) in the 2010/2011 survey and the 2015/2016 survey, respectively. The frequency of non-B subtypes increased from 42.9% in 2010/2011 to 54.8% in 2015/2016 (P < 0.001), including 23.4% and 30.6% of CRF02_AG (P = 0.004). The prevalence of virus with protease or reverse-transcriptase TDRAMs was 9.0% (95% CI = 6.8-11.2) in 2010/2011 and 10.8% (95% CI = 8.4-13.2) in 2015/2016 (P = 0.269). No significant increase was observed in integrase inhibitor TDRAMs (6.7% versus 9.2%, P = 0.146). Multivariable analysis showed that men infected with the B subtype were the group with the highest risk of being infected with a resistant virus compared with others (adjusted OR = 2.2, 95% CI = 1.3-3.9).Conclusions: In France in 2015/2016, the overall prevalence of TDRAMs was 10.8% and stable compared with 9.0% in the 2010/2011 survey. Non-B subtypes dramatically increased after 2010. Men infected with B subtype were the group with the highest risk of being infected with a resistant virus, highlighting the need to re-emphasize safe sex messages.
Published: 2018
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9. Emerging resistance mutations in PI-naive patients failing an atazanavir-based regimen (ANRS multicentre observational study)

Author: Lambert-Niclot, L, Grude, C, Chaix, L., Charpentier, L, Reigadas, C, Le Guillou-Guillemette, L, Rodallec, C, Maillard, Pascale, Dufayard, C, Mourez, C, Mirand, C, Guinard, L, Montes, S, Vallet, L, Marcelin, Marc, Descamps, L, Flandre, C, Delaugerre, L, Alloui, Chakib, Descamps, Diane, Charpentier, Charlotte, Visseaux, Benoit, Krivine, Anne, Bouviers-Alias, Ali, Pallier, Coralie, Soulié, Cathia, Wirden, Marc, Marcelin, Anne, Calvez, Vincent, Morand, Laurence, Lambert-Niclot, Sidonie, Fofana, Djeneba, Mahjoub, Nadia, Delaugerre, Constance, Chaix, Marie, Amiel, Corinne, Schneider, Veronique, Roussel, Catherine, Le Guillou-Guillemette, Hélène, Courdavault, Laurence, Reigadas, Sandrine, Recordon-Pinson, Patricia, Fleury, Hervé, Vallet, Sophie, Dina, Julia, Vabret, Astrid, Mirand, Audrey, Henquell, Cécile, Auvray, Christelle, de Rougemont, Alexis, Giraudon, Helene, Si-Mohammed, Ali, Mathez, Dominique, Signori-Schmuck, Anne, Morand, Patrice, Bocket, Laurence, Trabaud, Anne, Montes, Brigitte, Le Guen, Laura, Rodallec, Audrey, Ferré, Virginie, Jeulin, Hélène, SCHVOERER, Evelyne, Dufayard, Jacqueline, Allardet-Servent, Annick, carles, Marie, Guinard, Jérôme, Guigon, Aurélie, Giraudeau, Genevieve, Beby-Defaux, Agnès, Maillard, Anne, Plantier, Jean Christophe, Leoz, Marie, Mourez, Thomas, Bourlet, Thomas, Fafi-Kremer, Samira, Chiabrando, Julie, Raymond, Stéphanie, Izopet, Jacques, Barin, Francis, Marque-Juillet, Stéphanie, Yerly, Sabine, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Pontchaillou, Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Rouen, Normandie Université (NU), CHU Clermont-Ferrand, Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service de virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Mathématiques et Applications - ENS Paris (DMA), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Département d'Astrophysique, de physique des Particules, de physique Nucléaire et de l'Instrumentation Associée (DAPNIA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne (UB), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Victor Dupouy, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Laboratoire de Virologie Humaine et Moléculaire [Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de sérologie-virologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Raymond Poincaré [AP-HP], Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Département de virologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Service de Virologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Epidémiologie, Démographie et Sciences Sociales: santé reproductive, sexualité et infection à VIH (Inserm U569), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d'études démographiques (INED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Observatoire des Programmes Communautaires de Développement Rural (US ODR), Institut National de la Recherche Agronomique (INRA), Institut Pasteur de Nouvelle-Calédonie, Réseau International des Instituts Pasteur (RIIP), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Ecophysiologie Végétale, Agronomie et Nutritions (EVA), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Claude de Préval (ICP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université de Tours (UT), Centre Hospitalier de Versailles André Mignot (CHV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), École normale supérieure - Paris (ENS-PSL), Microbiologie Fondamentale et Pathogénicité (MFP), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Université Jean Monnet - Saint-Étienne (UJM), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université de Tours, Service de Virologie [CHU Pitié-Salpêtrière], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Lycée agricole La Touche, Hôpital Bichat - Claude Bernard, Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2, Memo-Flu-ARDS Study Group, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Tenon [APHP], Hôpital d'Argenteuil, Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital Raymond Poincaré [Garches], Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de virologie moléculaire et structurale, CHU Grenoble, Laboratoire de virologie [CHU Lille], Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national d'études démographiques (INED), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre national de référence du VIH INSERM U966, Centre Hospitalier de Versailles (CHV), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Microbiology (medical), Adult, Male, medicine.medical_specialty, 030106 microbiology, Atazanavir Sulfate, HIV Infections, Emtricitabine, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Abacavir, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Drug Resistance, Viral, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Treatment Failure, Tenofovir, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Pharmacology, business.industry, virus diseases, Lamivudine, HIV Protease Inhibitors, Middle Aged, Viral Load, Resistance mutation, Dideoxynucleosides, 3. Good health, Atazanavir, Regimen, Drug Combinations, Infectious Diseases, Mutation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Ritonavir, business, Viral load, medicine.drug
Abstract: Background Atazanavir is a PI widely used as a third agent in combination ART. We aimed to determine the prevalence and the patterns of resistance in PI-naive patients failing on an atazanavir-based regimen. Methods We analysed patients failing on an atazanavir-containing regimen used as a first line of PI therapy. We compared the sequences of reverse transcriptase and protease before the introduction of atazanavir and at failure [two consecutive viral loads (VLs) >50 copies/mL]. Resistance was defined according to the 2014 Agence Nationale de Recherche sur le SIDA et les Hepatites Virales (ANRS) algorithm. Results Among the 113 patients, atazanavir was used in the first regimen in 71 (62.8%) patients and in the first line of a PI-based regimen in 42 (37.2%). Atazanavir was boosted with ritonavir in 95 (84.1%) patients and combined with tenofovir/emtricitabine or lamivudine (n = 81) and abacavir/lamivudine or emtricitabine (n = 22). At failure, median VL was 3.05 log10 copies/mL and the median CD4+ T cell count was 436 cells/mm3. The median time on atazanavir was 21.2 months. At failure, viruses were considered resistant to atazanavir in four patients (3.5%) with the selection of the following major atazanavir-associated mutations: I50L (n = 1), I84V (n = 2) and N88S (n = 1). Other emergent PI mutations were L10V, G16E, K20I/R, L33F, M36I/L, M46I/L, G48V, F53L, I54L, D60E, I62V, A71T/V, V82I/T, L90M and I93L/M. Emergent NRTI substitutions were detected in 21 patients: M41L (n = 2), D67N (n = 3), K70R (n = 1), L74I/V (n = 3), M184V/I (n = 16), L210W (n = 1), T215Y/F (n = 3) and K219Q/E (n = 2). Conclusions Resistance to atazanavir is rare in patients failing the first line of an atazanavir-based regimen according to the ANRS. Emergent NRTI resistance-associated mutations were reported in 18% of patients.
Published: 2018
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10. Impact of Human Immunodeficiency Virus Type 1 Minority Variants on the Virus Response to a Rilpivirine-Based First-line Regimen

Author: Raymond, E, Nicot, F., Morand-Joubert, A, Rodallec, D, Mourez, M, Beby-Defaux, D, Lambert-Niclot, P, Charpentier, E, Malvé, B., Le Guillou-Guillemette, A, Si-Mohamed, D, Avettand Fenoel, A, Roussel, A., Calvez, P, Saune, E, Rodriguez, M, Descamps, E, Izopet, E, Lagier, E, Roussel, C, Le Guillou-Guillemette, G, Alloui, A., Bettinger, D., Pallier, P, Fleury, Frédéric, Reigadas, R, Bellecave, P., Recordon-Pinson, P, Payan, P, Vallet, S., Vabret, A., Dina, D, Henquell, C., Mirand, A., Bouvier-Alias, A, de Rougemont, A, Dos Santos, D, Morand, P, Signori-Schmuck, A., Bocket, B, Rogez, R, Andre, A, Tardy, C, Trabaud, A, Tamalet, C., Delamare, D, Montes, B, SCHVOERER, Evelyne, Ferré, F., André-Garnier, E., Cottalorda, C, Guinard, G, Guiguon, A, Descamps, D., Brun-Vézinet, B, Charpentier, c, Visseaux, B, Peytavin, G., Krivine, A., Si-Mohamed, A, Avettand-Fenoel, Véronique, Marcelin, A, Calvez, C, Lambert-Niclot, L, Soulié, C., Wirden, M., Morand-Joubert, M, Delaugerre, D, Chaix, M, Amiel, A, Schneider, S., Giraudeau, G, Beby- Defaux, D, Brodard, B, Maillard, A., Plantier, P, Chaplain, C, Bourlet, B, Fafi-Kremer, F, Stoll-Keller, F., Schmit, P, Barth, B, Yerly, S, Poggi, P., Izopet, I, Raymond, R, Barin, B, Chaillon, A, Marque-Juillet, M, Roque-Afonso, A, Haïm-Boukobza, B, Flandre, P., Grudé, G, Assoumou, A, Costagliola, D, Allegre, A, Schmit, J, Chennebault, M, Bouchaud, B, Magy-Bertrand, B, Delfraissy, D, Dupon, D, Morlat, P, Neau, D, Ansart, A., Jaffuel, J, Verdon, R, Jacomet, C, Lévy, L, Dominguez, D, Chavanet, P., Piroth, P, Cabié, A., Leclercq, P, Ajana, A, Cheret, A, Weinbreck, P, Cotte, C, Poizot-Martin, P, Ravaud, R., Christian, B, Truchetet, F, Grandidier, G, Rey, R., May, M, Goehringer, G, Raffi, F., Dellamonica, D, Prazuck, P, Hocqueloux, L, Landman, R, Yazdanpanah, Y., Launay, L, WEISS, L, Viard, P, Katlama, C., Simon, A., Girard, G, Meynard, M, Molina, M, Pialoux, G, Hoen, B., Goeger-Sow, G, Lamaury, I, Beaucaire, G, Le Moal, G., Jaussaud, R., Rouger, C, Michelet, M., Borsa-Lebas, B, Caron, F, Khuong, A., Lucht, F., Rey, D., Calmy, A, Lafeuillade, A, Marchou, B, Delobel, D, Gras, G, Greder-Belan, A, Vittecoq, D, Teiche, E, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de virologie [CHU Toulouse], CHU Toulouse [Toulouse], Hôpital Paul Brousse, CHU Bordeaux [Bordeaux], Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], Hospices Civils de Lyon (HCL), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universiatire Hôtel-Dieu de Nantes (CHU Hôtel-Dieu), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Rouen, Centre Hospitalier Universitaire de Lille (CHU de Lille), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Henri Mondor, CHU Pitié-Salpêtrière [AP-HP], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM UMR-S 606, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, PRES Sorbonne Paris-Cité, and Université Paris Denis Diderot, Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Virologie [AP-HP Hôpital Bichat-Claude-Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nancy (CHU Nancy), CHU Clermont-Ferrand, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Centre Hospitalier de Versailles André Mignot (CHV), Centre hospitalier universitaire de Grenoble (CHU de Grenoble), CHU Grenoble, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Necker, Centre Hospitalier Universitaire d'Amiens, Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses 94000 Créteil, France, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Agence Nationale de Recherches sur le SIDA et les hepatites virales (French National Agency for Research on AIDS and Viral Hepatitis, ANRS), Janssen-Cilag SAS, Erosion torrentielle neige et avalanches (UR ETGR (ETNA)), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de Pharmacologie Médicale, Institut National de la Santé et de la Recherche Médicale (INSERM)-Faculté de Médecine/CHU, CHU Besançon, Université de Franche-Comté (UFC), Génétique et évolution des interactions hôtes-parasites, Département génétique, interactions et évolution des génomes [LBBE] (GINSENG), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Laboratoire de Virologie Humaine et Moléculaire [Caen], Laboratoire de biologie structurale des interactions entre virus et cellule hôte, Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Génomique et épigénétique des pathologies placentaires (Inserm U709), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôtel-Dieu de Nantes, Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], CHU Necker - Enfants Malades [AP-HP], Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), AgroParisTech, T1, Laboratoire Matériaux Optiques, Photonique et Systèmes (LMOPS), CentraleSupélec-Université de Lorraine (UL)-CentraleSupélec-Université de Lorraine (UL), Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sciences pour l'environnement (SPE), Université Pascal Paoli (UPP)-Centre National de la Recherche Scientifique (CNRS), Département d'infectiologie (CHU de Dijon), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Laboratoire d'Acoustique de l'Université du Mans (LAUM), Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM), ONERA - The French Aerospace Lab [Toulouse], ONERA, Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), UMR CNRS 8179, Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies, Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Médecine Interne, Maladies Infectieuses et Tropicales (POTIERS - Mal Inf), Service de Médecine interne, Maladies Infectieuses et Immunologie Clinique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la Cognition Animale (CRCA), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University Hospital and University Jean Monnet, Laboratoire d'Ecologie Alpine (LECA), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Joseph Fourier - Grenoble 1 (UJF)-Université Grenoble Alpes (UGA), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Biologie structurale des interactions entre virus et cellule hôte (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Centre National de la Recherche Scientifique (CNRS)-Université Pascal Paoli (UPP), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), Laboratoire Chrono-environnement - CNRS - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Service de Médecine Interne, Maladies Infectieuses et Tropicales [CHU Poitiers], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ecologie Alpine (LECA ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hôpital de la Pitié-Salpêtrière, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)
Subjects: 0301 basic medicine, Male, Drug Resistance, HIV Infections, Drug resistance, Medical and Health Sciences, chemistry.chemical_compound, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 2.1 Biological and endogenous factors, Viral, Aetiology, Articles and Commentaries, ComputingMilieux_MISCELLANEOUS, minority resistant variants, Viral Load, Biological Sciences, first-line antiretroviral therapy, 3. Good health, Infectious Diseases, Rilpivirine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV/AIDS, Female, Infection, Viral hepatitis, Viral load, Microbiology (medical), Adult, ultra-deep sequencing, Microbiology, Virus, rilpivirine, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Clinical Research, Drug Resistance, Viral, Genetics, medicine, Humans, business.industry, Genetic Variation, medicine.disease, Virology, Reverse transcriptase, Regimen, Good Health and Well Being, 030104 developmental biology, chemistry, Mutation, HIV-1, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group, Antimicrobial Resistance, business
Abstract: Background Minority resistant variants of human immunodeficiency virus type 1 (HIV-1) could influence the virological response to treatment based on nonnucleoside reverse transcriptase inhibitors (NNRTIs). Data on minority rilpivirine-resistant variants are scarce. This study used next-generation sequencing (NGS) to identify patients harboring minority resistant variants to nucleos(t)ide reverse transcriptase inhibitors and NNRTIs and to assess their influence on the virological response (VR). Methods All the subjects, 541 HIV-1–infected patients started a first-line regimen containing rilpivirine. VR was defined as a HIV-1 RNA load Results NGS revealed resistance-associated mutations accounting for 1% to 20% in 29% of samples. We identified 43 (8.8%) and 36 (7.4%) patients who harbored rilpivirine-resistant variants with a 1% sensitivity threshold according to the French National Agency for Research on AIDS and Viral Hepatitis and Stanford algorithms, respectively. The VR was 96.9% at month 12. Detection of minority rilpivirine resistant variants was not associated with virological failure (VF). Multivariate analysis indicated that VF at month 12 was associated with a CD4 count Conclusions Minority resistant variants had no impact on the VR of treatment-naive patients to a rilpivirine-based regimen.
Published: 2018
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11. Maraviroc/raltegravir simplification strategy following 6 months of quadruple therapy with tenofovir/emtricitabine/maraviroc/raltegravir in treatment-naive HIV patients

Author: Pierre, Pradat, Jacques, Durant, Corinne, Brochier, Mary-Anne, Trabaud, Jacqueline, Cottalorda-Dufayard, Jacques, Izopet, François, Raffi, Frédéric, Lucht, Marie-Claude, Gagnieu, Caroline, Gatey, Christine, Jacomet, Matteo, Vassallo, Pierre, Dellamonica, Laurent, Cotte, M A, Trabaud, Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Motricité Humaine Expertise Sport Santé (LAMHESS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université de Toulon (UTLN)-Université Côte d'Azur (UCA), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), Hôpital Edouard Herriot [CHU - HCL], Service de maladies infectieuses et tropicales [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Université de Toulon (UTLN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Gabriel Montpied (CHU), Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Motricité Humaine Expertise Sport Santé ( LAMHESS ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Université de Toulon ( UTLN ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Groupe Immunité des Muqueuses et Agents Pathogènes ( GIMAP ), Université Jean Monnet [Saint-Étienne] ( UJM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Gabriel Montpied ( CHU ), and CHU Nice
Subjects: 0301 basic medicine, Male, HIV Infections, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Raltegravir Potassium, Maraviroc, chemistry.chemical_compound, 0302 clinical medicine, Maintenance therapy, Antiretroviral Therapy, Highly Active, Clinical endpoint, Medicine, Emtricitabine, Pharmacology (medical), 030212 general & internal medicine, virus diseases, Middle Aged, Viral Load, 3. Good health, virology, Infectious Diseases, Treatment Outcome, Viruses, Female, France, Viral load, medicine.drug, Microbiology (medical), Adult, medicine.medical_specialty, Adolescent, Patients, Anti-HIV Agents, 030106 microbiology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Tropism, Maintenance Chemotherapy, methods, 03 medical and health sciences, Young Adult, Cyclohexanes, Internal medicine, Humans, Adverse effect, Tenofovir, therapy, business.industry, Hiv, Triazoles, Raltegravir, chemistry, Mutation, HIV-1, pharmacology, business
Abstract: International audience; OBJECTIVE: We assessed the virological efficacy of a 6 month maraviroc/raltegravir simplification strategy following 6 months of quadruple therapy combining tenofovir disoproxil fumarate/emtricitabine with maraviroc/raltegravir. METHODS: HIV-1-infected naive patients were enrolled in an open label, single-arm, Phase 2 trial. All patients received maraviroc 300 mg twice daily, raltegravir 400 mg twice daily and tenofovir/emtricitabine for 24 weeks. Patients with stable HIV-RNA \\textless50 copies/mL stopped tenofovir/emtricitabine at week (W) 24 and pursued maraviroc/raltegravir until W48. The primary endpoint was the virological response defined by HIV-RNA \\textless50 copies/mL at W48. RESULTS: Thirty-three patients were analysed. Patients were mostly male (94%), Caucasians (91%), MSM (82%); their median age was 42 years. At baseline, median CD4 cell count was 453 cells/mm3 and HIV-RNA was 4.3 log copies/mL. All patients had CCR5-tropic viruses by genotropism and phenotropism assays. All but one patient had an HIV-RNA \\textless 50 copies/mL at W24 and entered the simplification phase. Virological success was maintained at W48 in 88% (90% CI 79%-97%) of patients. N155H mutation was detected at failure in one patient. No tropism switch was observed. Raltegravir and maraviroc plasma exposure were satisfactory in 92% and 79% of 41 samples from 21 patients. Five severe adverse events (SAEs) were observed up to W48; none was related to the study drugs. Four patients presented grade 3 AEs; none was related to the study. No grade 4 AE was observed. No patient died. CONCLUSIONS: Maraviroc/raltegravir maintenance therapy following a 6 month induction phase with maraviroc/raltegravir/tenofovir/emtricitabine was well tolerated and maintained virological efficacy in these carefully selected patients
Published: 2016
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12. Performance of genotypic algorithms for predicting tropism for HIV-1 CRF01_AE recombinant

Author: Samira Fafi-Kremer, Laurence Morand-Joubert, Audrey Mirand, Vincent Calvez, Cathia Soulié, Mary-Anne Trabaud, A G Marcelin, Jacqueline Cottalorda, Anne Signori-Schmuck, S. Berger, Julia Dina, Coralie Pallier, Véronique Avettand-Fenoel, Brigitte Montes, Pantxika Bellecave, Karen Zafilaza, Charlotte Charpentier, L. Le Guen, Sabine Yerly, Catherine Roussel, Corinne Amiel, Sophie Sayon, Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie pédiatrique [Hôpital Lapeyronie-Arnaud de Villeneuve], Hôpital Lapeyronie [Montpellier] (CHU), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Virologie [Strasbourg], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Equipe de Recherche en Physico-Chimie et Biotechnologie (ERPCB), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), UR 0420 - Station de pathologie végétale, Laboratoire de pathologie forestière, Institut National de la Recherche Agronomique (INRA)-Institut National de la Recherche Agronomique (INRA), Neuroimagerie cognitive (LCogn), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de biologie structurale des interactions entre virus et cellule hôte, Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Saint-Gobain Recherche (SGR), SAINT-GOBAIN, CHU Pitié-Salpêtrière [APHP], Service de virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biologie structurale des interactions entre virus et cellule hôte (UVHCI), European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Microbiologie Fondamentale et Pathogénicité (MFP), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Saint-Gobain, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Genotype, Genotyping Techniques, viruses, Concordance, 030106 microbiology, Human immunodeficiency virus (HIV), HIV Infections, ddc:616.07, HIV Envelope Protein gp120, Biology, medicine.disease_cause, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Virology, HIV tropism, medicine, Humans, False Positive Reactions, 030212 general & internal medicine, Tropism, ComputingMilieux_MISCELLANEOUS, virus diseases, Viral Load, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, CD4 Lymphocyte Count, 3. Good health, Viral Tropism, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Recombinant DNA, RNA, Viral, France, False positive rate, Viral load, Algorithm, Algorithms, Switzerland, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objectives There is no consensus about the performances of genotypic rules for predicting HIV-1 non-B subtype tropism. Three genotypic methods were compared for CRF01_AE HIV-1 tropism determination. Methods The V3 env region of 207 HIV-1 CRF01_AE and 178 B subtypes from 17 centers in France and 1 center in Switzerland was sequenced. Tropism was determined by Geno2Pheno algorithm with false positive rate (FPR) 5% or 10%, the 11/25 rule or the combined criteria of the 11/25, net charge rule and NXT/S mutations. Results Overall, 72.5%, 59.4%, 86.0%, 90.8% of the 207 HIV-1 CRF01_AE were R5-tropic viruses determined by Geno2pheno FPR5%, Geno2pheno FPR10%, the combined criteria and the 11/25 rule, respectively. A concordance of 82.6% was observed between Geno2pheno FPR5% and the combined criteria for CRF01_AE. The results were nearly similar for the comparison between Geno2pheno FPR5% and the 11/25 rule. More mismatches were observed when Geno2pheno was used with the FPR10%. Neither HIV viral load, nor current or nadir CD4 was associated with the discordance rate between the different algorithms. Conclusion Geno2pheno predicted more X4-tropic viruses for this set of CRF01_AE sequences than the combined criteria or the 11/25 rule alone. For a conservative approach, Geno2pheno FPR5% seems to be a good compromise to predict CRF01_AE tropism.
Published: 2018

13. Comparison of HIV-1 drug-resistance genotyping by ultra-deep sequencing and sanger sequencing using clinical samples

Author: Jean-Claude Tardy, Patrice Andre, Vinca Icard, Christophe Ramière, Mary-Anne Trabaud, Caroline Scholtes, Laboratoire de Virologie [HCL-Hôpital de la Croix Rousse], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Biologie cellulaire des infections virales – Cell biology of viral infection, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, Genotype, Genotyping Techniques, Anti-HIV Agents, 030106 microbiology, Population, education, Human immunodeficiency virus (HIV), Drug Resistance, HIV Infections, Drug resistance, Biology, medicine.disease_cause, 03 medical and health sciences, symbols.namesake, Virology, Drug Resistance, Viral, medicine, data visualization, Humans, Viral, Genotyping, Sanger sequencing, software tools, education.field_of_study, High-Throughput Nucleotide Sequencing, Reproducibility of Results, Ultra deep sequencing, Viral Load, mutations, Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Reverse transcriptase, 3. Good health, Infectious Diseases, Mutation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, symbols, HIV-1, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, data management, Viral load, Software
Abstract: International audience; Sanger population sequencing (SPS) is the reference technique to monitor HIV-1-infected patients' therapy. Ultra-deep sequencing (UDS), which allows quantitative detection of drug resistance mutations, may be an alternative method. The study aimed to compare reproducibility and predictions of UDS versus SPS in a routine setting. A control containing low-abundance variants was repeatedly tested and clinical plasma samples from 100 patients were prospectively assayed by SPS and UDS using the Roche 454 system. Complete analysis by UDS was available for 88% of samples with various viral loads and subtypes. Comparison of detection thresholds found that SPS sensitivity was variable. Variations found by UDS between 5% to \textgreater20% were detected by SPS in 25% to more than 80% of samples. At the 5% cut-off, disagreements were rare and in most cases UDS detected an additional protease secondary mutation, suggesting a possible resistance to a protease inhibitor according to the 2015 ANRS algorithm. Mutations found on reverse transcriptase by only UDS were often explained by previous therapy. UDS with a variant detection threshold at 5% might allow therapy management with minimal differences compared to population sequencing while providing additional information for further determination of pertinent cutoff values for specific resistance mutations.
Published: 2017
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14. Prevalence of HIV-1 drug resistance in treated patients with viral load >50 copies/mL: a 2014 French nationwide study

Author: Assoumou, L., Charpentier, C., Recordon-Pinson, P., Grude, M., Pallier, C., Morand-Joubert, L., Fafi-Kremer, S., Krivine, A., Montes, B, Ferre, V., Bouvier-Alias, M., Plantier, C., Izopet, J., Trabaud, M., Yerly, S., Dufayard, J., Alloui, C., Courdavault, L., Le Guillou-Guillemette, H., Maillard, A., Amiel, C., Vabret, A., Roussel, C., Vallet, S., Guinard, J., Mirand, A., Beby-Defaux, A., Barin, F., Allardet-Servent, A., Ait-Namane, R., Wirden, M., Delaugerre, C., Calvez, V., Chaix, L., Descamps, D., Reigadas, S., Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroimagerie cognitive (LCogn), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [Strasbourg], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Equipe de Recherche en Physico-Chimie et Biotechnologie (ERPCB), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire de Virologie Humaine et Moléculaire [Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), UR 0420 - Station de pathologie végétale, Laboratoire de pathologie forestière, Institut National de la Recherche Agronomique (INRA)-Institut National de la Recherche Agronomique (INRA), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), CHU Orléans, CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de microbiologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital Cochin [AP-HP], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département de microbiologie [CHU Rouen], CHU Rouen, Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpitaux Universitaires de Genève (HUG), Hôpital l'Archet, Hôpital Avicenne [AP-HP], Centre Hospitalier Victor Dupouy, CHU Pontchaillou [Rennes], CHU Tenon [AP-HP], CHU Amiens-Picardie, Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Microbiologie Fondamentale et Pathogénicité (MFP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), CHU Cochin [AP-HP], T1, Laboratoire Matériaux Optiques, Photonique et Systèmes (LMOPS), CentraleSupélec-Université de Lorraine (UL)-CentraleSupélec-Université de Lorraine (UL), CHU Tenon [APHP], Station de recherches sur la vache laitière, Institut National de la Recherche Agronomique (INRA), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), and CHU Pitié-Salpêtrière [APHP]
Subjects: 0301 basic medicine, Microbiology (medical), Adult, Male, Genes, Viral, Genotype, Anti-HIV Agents, 030106 microbiology, HIV Infections, HIV Integrase, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, 03 medical and health sciences, 0302 clinical medicine, Drug Resistance, Multiple, Viral, HIV Protease, Antiretroviral Therapy, Highly Active, Humans, Pharmacology (medical), 030212 general & internal medicine, Treatment Failure, ComputingMilieux_MISCELLANEOUS, Pharmacology, Sequence Analysis, DNA, Middle Aged, Viral Load, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, HIV Reverse Transcriptase, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, RNA, Viral, Reverse Transcriptase Inhibitors, Female, France, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Surveillance of HIV-1 resistance in treated patients with a detectable viral load (VL) is important to monitor, in order to assess the risk of spread of resistant viruses and to determine the proportion of patients who need new antiretroviral drugs with minimal cross-resistance.The HIV-1 protease and reverse transcriptase (RT) and integrase genes were sequenced in plasma samples from 782 consecutive patients on failing antiretroviral regimens, seen in 37 specialized centres in 2014. The genotyping results were interpreted using the ANRS v24 algorithm. Prevalence rates were compared with those obtained during a similar survey conducted in 2009.The protease and RT sequences were obtained in 566 patients, and the integrase sequence in 382 patients. Sequencing was successful in 60%, 78%, 78% and 87% of patients with VLs of 51-200, 201-500, 501-1000 and1000 copies/mL, respectively. Resistance to at least one antiretroviral drug was detected in 56.3% of samples. Respectively, 3.9%, 8.7%, 1.5% and 3.4% of patients harboured viruses that were resistant to any NRTI, NNRTI, PI and integrase inhibitor (INI). Resistance rates were lower in 2014 than in 2009. Resistance was detected in 48.5% of samples from patients with a VL between 51 and 200 copies/mL.In France in 2014, 90.0% of patients in AIDS care centres were receiving antiretroviral drugs and 12.0% of them had VLs50 copies/mL. Therefore, this study suggests that 6.7% of treated patients in France might transmit resistant strains. Resistance testing may be warranted in all treated patients with VL 50 copies/mL.
Published: 2017
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15. Antiretroviral-treated HIV-1 patients can harbour resistant viruses in CSF despite an undetectable viral load in plasma

Author: Sabine Yerly, Maxime Grude, Audrey Mirand, Philippe Flandre, Anne Maillard, Aurélie Guigon, Sandrine Reigadas, Corinne Amiel, Chakib Alloui, Samira Fafi-Kremer, Stéphanie Haim-Boukobza, Stéphanie Raymond, Anne Signori-Schmuck, Hélène Jeulin, Laurence Morand-Joubert, Virginie Ferré, Catherine Roussel, Brigitte Montes, Pantxika Bellecave, Anne-Geneviève Marcelin, Sophie Vallet, Diane Descamps, Lambert Assoumou, Mary-Anne Trabaud, Vincent Calvez, Cathia Soulié, Francis Barin, Constance Delaugerre, Coralie Pallier, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, CHU Tenon [AP-HP], CHU Saint-Antoine [AP-HP], Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Virologie [Hôpital Paul-Brousse - APHP] (World Health Organization Rubella National Reference Laboratory), Hôpital Paul Brousse, CHU Bordeaux [Bordeaux], Service de virologie et unité de surveillance biologique [Bordeaux], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Department of Infectious Diseases [Paris], Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Virologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de virologie CHU de NANCY BRADOIS, Service de bactériologie-Virologie-Hygiène [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Geneva University Hospital (HUG), Département de virologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Orléans, Laboratoire de Virologie [Strasbourg], CHU Clermont-Ferrand, CHU Pontchaillou [Rennes], CHU-BREST-Service de Virologie, and CHU Amiens-Picardie
Subjects: Adult, Male, Microbiology (medical), Genotype, Genotyping Techniques, Population, Human immunodeficiency virus (HIV), HIV Infections, Microbial Sensitivity Tests, Drug resistance, Biology, medicine.disease_cause, Plasma, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Resistance, Viral, HIV encephalitis, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Sida, education, Cognitive impairment, Cerebrospinal Fluid, Retrospective Studies, Pharmacology, education.field_of_study, Middle Aged, Viral Load, biology.organism_classification, Virology, Infectious Diseases, Anti-Retroviral Agents, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunology, HIV-1, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, France, Viral load, Switzerland, 030217 neurology & neurosurgery
Abstract: International audience; Background: HIV therapy reduces the CSF HIV RNA viral load (VL) and prevents disorders related to HIV encephalitis. However, these brain disorders may persist in some cases. A large population of antiretroviral-treated patients who had a VL > 1.7 log10 copies/mL in CSF with detectable or undetectable VL in plasma associated with cognitive impairment was studied, in order to characterize discriminatory factors of these two patient populations.Methods: Blood and CSF samples were collected at the time of neurological disorders for 227 patients in 22 centres in France and 1 centre in Switzerland. Genotypic HIV resistance tests were performed on CSF. The genotypic susceptibility score was calculated according to the last Agence Nationale de Recherche sur le Sida et les hépatites virales Action Coordonnée 11 (ANRS AC11) genotype interpretation algorithm.Results: Among the 227 studied patients with VL > 1.7 log10 copies/mL in CSF, 195 had VL detectable in plasma [median (IQR) HIV RNA was 3.7 (2.7–4.7) log10 copies/mL] and 32 had discordant VL in plasma (VL 1.7 log10 copies/mL. Resistance to antiretrovirals was observed in CSF for the two groups of patients.Conclusions: Fourteen percent of this population of patients with cognitive impairment and detectable VL in CSF had well controlled VL in plasma. Thus, it is important to explore CSF HIV (VL and genotype) even if the HIV VL is controlled in plasma because HIV resistance may be observed.
Published: 2017
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16. HIV-1 sequences isolated from patients promote expression of shorter isoforms of the Gag polyprotein

Author: Théophile Ohlmann, Mary-Anne Trabaud, Christelle Daudé, Didier Decimo, Sylvain de Breyne, Patrice Andre, Contrôle traductionnel des ARNm eucaryotes et viraux – Translational control of Eukaryotic and Viral RNAs, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Integrated Physiology of the Brain Arousal Systems (WAKING), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Hospices Civils de Lyon (HCL), Biologie cellulaire des infections virales – Cell biology of viral infection, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Team Waking [Lyon], Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Gene isoform, Male, Translational efficiency, viruses, Gene Expression, HIV Infections, Biology, gag Gene Products, Human Immunodeficiency Virus, 03 medical and health sciences, Jurkat Cells, Eukaryotic translation, Virology, Coding region, Humans, Protein Isoforms, Viral, Cloning, Molecular, gag Gene Products, Messenger RNA, Expression vector, 030102 biochemistry & molecular biology, Molecular, Translation (biology), Sequence Analysis, DNA, General Medicine, DNA, Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Internal ribosome entry site, 030104 developmental biology, Protein Biosynthesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, RNA, Viral, RNA, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Sequence Analysis, Human Immunodeficiency Virus, Cloning
Abstract: International audience; Human immunodeficiency virus type 1 (HIV-1) unspliced mRNA drives the expression of both Gag and Gag-Pol polyproteins by using both cap- and internal ribosome entry site (IRES)-dependent translation initiation mechanisms. An IRES has been described in the matrix coding region that is involved in the production of shorter isoforms of Gag. However, up to now, this has only been shown with sequences derived from the HIV-1 laboratory strains (NL4.3 and HXB2) and never from clinical HIV-1 isolates. We have isolated ~70 sequences from HIV-1-positive patients that we have sequenced and cloned into an expression vector to monitor their ability to drive translation of Gag p55 and the shorter isoforms both in vitro and ex vivo. The results indicate that (1) the translational efficiency from the AUG-p55 varies significantly among the different isolates; (2) expression initiated at AUG-p40 codon is independent of translation initiation at the AUG-p55 triplet; and (3) all sequences promote expression of shorter Gag isoforms, in particular in Jurkat T cells, in which internal initiation occurs exclusively and directly at the AUG-p40 codon. The composition of the first ~800 nucleotides of the HIV-1 unspliced mRNA modulates the expression initiated both at the AUG-p55 and AUG-p40 codons and may impact viral production and replication. Interestingly, the AUG-p40 codon and its surrounding nucleotide context are conserved amongst clinical isolates and are used as a translation initiation site to produce a shorter Gag isoform.
Published: 2016
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17. Different effects of the TAR structure on HIV-1 and HIV-2 genomic RNA translation

Author: Taran Limousin, Théophile Ohlmann, Ricardo Soto-Rifo, Didier Decimo, Emiliano P. Ricci, Olivier Moncorgé, Andrea Cimarelli, Mary-Anne Trabaud, Paulina S. Rubilar, Patrice Andre, Virologie humaine, École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Université de Lyon, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Aptanomics, and CIMARELLI, Andrea
Subjects: Five prime untranslated region, [SDV]Life Sciences [q-bio], viruses, medicine.disease_cause, gag Gene Products, Human Immunodeficiency Virus, Ribosome, MESH: HIV-1, MESH: Proviruses, Proviruses, MESH: HIV-2, Protein biosynthesis, MESH: Animals, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, 0303 health sciences, MESH: HIV Long Terminal Repeat, 030302 biochemistry & molecular biology, MESH: gag Gene Products, Human Immunodeficiency Virus, 3. Good health, MESH: RNA, Viral, MESH: Protein Biosynthesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, MESH: 5' Untranslated Regions, MESH: Genome, Viral, HIV Long Terminal Repeat, Viral protein, Genome, Viral, Biology, Cell Line, 03 medical and health sciences, medicine, Animals, Humans, Post-transcriptional regulation, 030304 developmental biology, MESH: Humans, RNA, Virology, MESH: Cell Line, Viral replication, Protein Biosynthesis, HIV-2, HIV-1, 5' Untranslated Regions, Ribosomes, MESH: Ribosomes
Abstract: International audience; The 5′-untranslated region (5′-UTR) of the genomic RNA of human immunodeficiency viruses type-1 (HIV-1) and type-2 (HIV-2) is composed of highly structured RNA motifs essential for viral replication that are expected to interfere with Gag and Gag-Pol translation. Here, we have analyzed and compared the properties by which the viral 5′-UTR drives translation from the genomic RNA of both human immunodeficiency viruses. Our results showed that translation from the HIV-2 gRNA was very poor compared to that of HIV-1. This was rather due to the intrinsic structural motifs in their respective 5′-UTR without involvement of any viral protein. Further investigation pointed to a different role of TAR RNA, which was much inhibitory for HIV-2 translation. Altogether, these data highlight important structural and functional differences between these two human pathogens.
Published: 2011
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18. Increasing prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-infected patients from 2001 to 2006/2007 in France

Author: Jacques Izopet, Jacqueline Cottalorda, Vincent Calvez, Charlotte Charpentier, Henia Saoudin, Georges Dos Santos, Mary-Anne Trabaud, Francis Barin, V. Calvez, Cécile Henquell, Delphine Desbois, C. Delaugerre, Slim Fourati, D. Bettinger, Thomas Bourlet, Anne Krivine, Bernard Masquelier, S. Vallet, M. Bouvier-Alias, Catherine Tamalet, B. Masquelier, S. Rogez, Coralie Pallier, J. C. Plantier, C. Charpentier, F. Barin, J. Cottalorda, A. Maillard, Alexandre Storto, G. DosSantos, Chakib Alloui, B. Montes, Marie-Laure Chaix, A. G. Marcelin, Anne Signori-Schmuck, D. Desbois, Anne-Geneviève Marcelin, Marie Laure Chaix, C. Tamalet, F. Brun-Vézinet, Françoise Brun-Vézinet, J. Izopet, Philippe Flandre, G. Anies, Anne Maillard, Diane Descamps, Patrice Andre, Jean-Claude Tardy, Dominique Costagliola, Brigitte Montes, Laurence Morand-Joubert, Annick Ruffault, Jean-Christophe Plantier, Sophie Pakianather, L. Morand-Joubert, and Constance Delaugerre
Subjects: Male, Microbiology (medical), Anti-HIV Agents, HIV Infections, Drug resistance, Nucleoside Reverse Transcriptase Inhibitor, 03 medical and health sciences, 0302 clinical medicine, HIV Protease, Drug Resistance, Viral, HIV Seropositivity, Prevalence, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Pharmacology, 0303 health sciences, Reverse-transcriptase inhibitor, biology, 030306 microbiology, Proteolytic enzymes, biology.organism_classification, Virology, HIV Reverse Transcriptase, Reverse transcriptase, 3. Good health, Infectious Diseases, Chronic Disease, Mutation, Immunology, Lentivirus, HIV-1, Reverse Transcriptase Inhibitors, Female, France, Viral disease, Viral load, medicine.drug
Abstract: Objectives: To estimate the prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-1-infected patients in France. Methods: Resistance mutations were sought in samples from 530 newly diagnosed HIV-1-infected patients from October 2006 to March 2007. Protease and reverse transcriptase mutations were identified from the 2007 Stanford Resistance Surveillance list. Results: Reverse transcriptase and protease resistance mutations were determined in 466 patients with duration of seropositivity
Published: 2010
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19. Evaluation of the Genotypic Prediction of HIV-1 Coreceptor Use versus a Phenotypic Assay and Correlation with the Virological Response to Maraviroc: the ANRS GenoTropism Study

Author: Recordon-Pinson, Patricia, Soulié, Cathia, Flandre, Philippe, Descamps, Diane, Lazrek, Mouna, Charpentier, Charlotte, Montes, Brigitte, Trabaud, Mary-Anne, Cottalorda, Jacqueline, Schneider, Véronique, Morand-Joubert, Laurence, Tamalet, Catherine, Desbois, Delphine, Macé, Muriel, Ferré, Virginie, Vabret, Astrid, Ruffault, Annick, Pallier, Coralie, Raymond, Stéphanie, Izopet, Jacques, Reynes, Jacques, Marcelin, Anne-Geneviève, Masquelier, Bernard, Renseigné, Non, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de microbiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Virology Laboratory, Hôpital Rothchild, Service de bactériologie-virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Virology, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Human and Molecular Virology, Georges Clémenceau Universitary Hospital, Unité de Rétrovirologie, Hôpital Pontchaillou, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Laboratoire de Virologie, Institut Fédératif de Biologie de Purpan, Variabilité génomique des virus, Université Bordeaux Segalen - Bordeaux 2-IFR66, Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Microbiologie Fondamentale et Pathogénicité (MFP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Oncology, MESH: Sequence Analysis, DNA, Multivariate analysis, HIV Infections, HIV Envelope Protein gp120, MESH: Receptors, CCR5, Maraviroc, MESH: Genotype, MESH: HIV-1, Correlation, MESH: HIV Envelope Protein gp120, chemistry.chemical_compound, HIV Protease, HIV Fusion Inhibitors, Genotype, MESH: Receptors, HIV, Pharmacology (medical), MESH: Treatment Outcome, 0303 health sciences, MESH: Middle Aged, MESH: Tropism, MESH: HIV Infections, Middle Aged, MESH: Cyclohexanes, HIV Reverse Transcriptase, 3. Good health, Phenotype, Treatment Outcome, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, CCR5 Receptor Antagonists, Lentivirus, Female, Viral load, Adult, medicine.medical_specialty, Receptors, CCR5, MESH: HIV Reverse Transcriptase, Molecular Sequence Data, CCR5 receptor antagonist, Biology, MESH: Phenotype, Antiviral Agents, Sensitivity and Specificity, Tropism, MESH: HIV Protease, 03 medical and health sciences, Receptors, HIV, Cyclohexanes, Internal medicine, medicine, Humans, MESH: HIV Fusion Inhibitors, 030304 developmental biology, Pharmacology, MESH: Humans, MESH: Molecular Sequence Data, 030306 microbiology, MESH: Adult, Sequence Analysis, DNA, Triazoles, biology.organism_classification, Virology, MESH: Male, MESH: Sensitivity and Specificity, MESH: Triazoles, chemistry, Expanded access, HIV-1, MESH: Female
Abstract: Genotypic algorithms for prediction of HIV-1 coreceptor usage need to be evaluated in a clinical setting. We aimed at studying (i) the correlation of genotypic prediction of coreceptor use in comparison with a phenotypic assay and (ii) the relationship between genotypic prediction of coreceptor use at baseline and the virological response (VR) to a therapy including maraviroc (MVC). Antiretroviral-experienced patients were included in the MVC Expanded Access Program if they had an R5 screening result with Trofile (Monogram Biosciences). V3 loop sequences were determined at screening, and coreceptor use was predicted using 13 genotypic algorithms or combinations of algorithms. Genotypic predictions were compared to Trofile; dual or mixed (D/M) variants were considered as X4 variants. Both genotypic and phenotypic results were obtained for 189 patients at screening, with 54 isolates scored as X4 or D/M and 135 scored as R5 with Trofile. The highest sensitivity (59.3%) for detection of X4 was obtained with the Geno2pheno algorithm, with a false-positive rate set up at 10% (Geno2pheno10). In the 112 patients receiving MVC, a plasma viral RNA load of
Published: 2010
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20. Factors Associated with Virological Response to Etravirine in Nonnucleoside Reverse Transcriptase Inhibitor-Experienced HIV-1-Infected Patients

Author: Charlotte Charpentier, Bernard Masquelier, Philippe Flandre, Dominique Bettinger, Cécile Henquell, Vincent Calvez, Annick Ruffault, Georges Dos Santos, Henia Saoudin, Sophie Vallet, Francis Barin, Jacques Izopet, Sylvie Rogez, Diane Descamps, Chakib Alloui, Catherine Tamalet, Anne Signori-Schmuck, Mary-Anne Trabaud, Jacqueline Cottalorda, Constance Delaugerre, Anne-Geneviève Marcelin, Magali Bouvier-Alias, and Laurence Morand-Joubert
Subjects: Male, Oncology, medicine.medical_specialty, Enfuvirtide, Genotype, Anti-HIV Agents, Etravirine, HIV Infections, Biology, Antiviral Agents, Nucleoside Reverse Transcriptase Inhibitor, 03 medical and health sciences, Interquartile range, Internal medicine, Drug Resistance, Viral, Nitriles, medicine, Humans, Pharmacology (medical), Phylogeny, Darunavir, 030304 developmental biology, Pharmacology, 0303 health sciences, Reverse-transcriptase inhibitor, Reverse Transcriptase Polymerase Chain Reaction, 030306 microbiology, virus diseases, Raltegravir, Virology, HIV Reverse Transcriptase, Reverse transcriptase, 3. Good health, Pyridazines, Pyrimidines, Treatment Outcome, Infectious Diseases, Mutation, HIV-1, RNA, Viral, Reverse Transcriptase Inhibitors, Female, medicine.drug
Abstract: To identify factors associated with virological response (VR) to an etravirine (ETR)-based regimen, 243 patients previously treated with nonnucleoside reverse transcriptase inhibitors (NNRTIs) were studied. The impact of baseline HIV-1 RNA, CD4 cell count, past NNRTIs used, 57 NNRTI resistance mutations, genotypic sensitivity score (GSS) for nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), and the number of new drugs used with ETR for the first time on the VR to an ETR regimen were investigated. Among the 243 patients, the median baseline HIV-1 RNA level was 4.4 log10copies/ml (interquartile range [IQR], 3.7 to 4.9) and the median CD4 count was 175 cells/mm3(IQR, 69 to 312). Patients had been previously exposed to a median of 6 NRTIs, 1, NNRTI, and 5 PIs. Overall, 82% of patients achieved a VR at month 2, as defined by a decrease of at least 1.5 log10copies/ml and/or HIV-1 RNA level of
Published: 2010
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21. HIV-1 subtype B-infected MSM may have driven the spread of transmitted resistant strains in France in 2007–12: impact on susceptibility to first-line strategies

Author: Frange, Pierre, Assoumou, Pierre, Descamps, Diane, Chéret, Antoine, Goujard, Cécile, Tran, Laurent, Gousset, Marine, Avettand-Fenoël, Véronique, Bocket, Laurence, Tran, Samira, Guinard, Jérôme, Morand-Joubert, Pierre, Nicot, Florence, Plantier, Jean-Christophe, Rogez, Sylvie, Wirden, Pierre, Rouzioux, Christine, Meyer, Laurence, Chaix, Marie-Laure, Abel, S., Abraham, B., Antoniotti, A., Armero, R., Audhuy, B., Aumaitre, H., Beaucaire, G., Beck-Wirth, G., Berger, J.L., Bernard, L., Beuscart, C., Bodard, L., Bouchaud, O., Boue, F., Cabane, J.-P., Cabié, A., Champagne, H., Cheneau, C., Chennebault, J.-M., Cheret, A., Christian, B., Compagnucci, A., Daneluzzi, V., Debab, Y., Dellamonica, P., Delfraissy, F., Devidas, A., Diab, G., Doll, J., Drobacheff-Thebaut, C., Durel, A., Esnault, L., Faba, L., Froguel, E., Garipuy, D., Garrait, V., Geffray, L., Genet, C., Genet, P., Gérard, L., Ghosn, J., Girard, J., Girard, Pascal, Godin-Collet, C., Hochedez, P., Hoen, B., Houlbert, D., Jacomet, C., Jeantils, V., Jidar, K., Klement, E., Lafeuillade, A., Launay, V., Leprêtre, A., Levy, Y., Makhloufi, D., Malbec, D., Martha, B., May, T., Merrien, D., Miailhes, P., Miodovski, C., Morlat, P., Mortier, E., Neau, D., Obadia, M., Patey, O., Pellegrin, L., Perronne, V., Philibert, P., Pialoux, G., Pichancourt, G., Piroth, L., Poinsignon, Y., Poizot-Martin, I., Prazuck, T., Prendki, V., Du Clary, F., Quinsat, D., Regnier, A., Reynes, J., Rosenthal, E., Rouveix, E., Salmon, D., Salanville, F., Schmitt, L., Simon-Coutellier, A., Sotto, A., Souala, F., Stein, A., Timsit, F., de Truchis, P., Uludag, A., Vaillant, O., Verdon, R., Verlesch-Langlin, A., Viard, J.-P., Vittecoq, D., Weiss, L., Yéni, P., Zucman, D., Allavena, C., Allegre, T., Amri, I., Autran, B., Bacchus, C., Blanc, C., Bonne, S., Bonne, B., Bouchez, S., Charlier, C., Consigny, H., Duvivier, C., Fourn, E., Guiroy, F., Huleux, T., Katlama, C., Lascoux, C., Leplatois, A., Lyavanc, T., Molina, J.-M., Naqvi, A., Nembot, G., Quertainmont, Y., Raffi, F., Samri, A., Schneider, L., Seang, S., Seksik, B., Shoai-Tehrani, M., Slama, L., Valentin, A., Yazdanpanah, Y., Alloui, C., Amiel, C., André, P., André, E., Anies, G., Barin, F., Bellecave, P., Bettinger, D., Bouvier-Alias, M., Brun-Vézinet, F., Calmy, A., Calvez, V., Caveng, W., Chaillon, A., Chapalay, S., Charpentier, C., Costagliola, D., Cottalorda, J., Delamare, C., Delaugerre, C., Dina, J., Santos, G., Ferre, V., Flandre, P., Fleury, H., Fourati, S., Gaille, C., Giraudeau, G., Guigon, A., Haim-Boukobza, S., Lagier, E., Le Guillou-Guillemette, H., Henquell, C., Izopet, Jacques, Lambert-Niclot, Lambert, Leroux, M., Maillard, A., Malet, I., Marcelin, Marc, Marque-Juillet, S., Masquelier, B., Mirand, A., Morand, P., Montes, B, Mouna, L., Noel, C., Pallier, C., Peytavin, G., Pinson-Recordon, P., Poveda, J., Raymond, S., Reigadas, S., Roques, A., de Rougemont, A., Roussel, C., Schmitt, P., Schneider, V., Schvoerer, E., Signori-Schmuck, A., Soulié, C., Tamalet, C., Tardy, C., Trabaud, A., Vabret, A., Vallet, S., Yerly, S., Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Virologie [CHU Necker], Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Service de microbiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de médecine interne et maladies infectieuses, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Departement d'épidémiologie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Laboratoire de virologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Labex_Transplantex (Labex_Transplantex), Laboratoire de Virologie [Strasbourg], Laboratoire de microbiologie [CHRU Orléans], Centre Hospitalier Régional d'Orléans (CHRO), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire de virologie [CHU Toulouse], CHU Toulouse [Toulouse], Coordination Régionale de la lutte contre l'infection due au VIH (COREVIH), COREVIH, Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Microbiologie Clinique, Laboratoire de Virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Système membranaires, photobiologie, stress et détoxication (SMPSD), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Département de Pharmacie, inconnu, Inconnu, Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Service des maladies infectieuses et tropicales, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hopital l'Archet, Centre d'Information et de Soins de I'Immunodéficience Humaine (CISIH). Hôpital l'Archet 1, Hôpital l'Archet, Service des Maladies infectieuses et tropicales [CHU Limoges], Infectious Diseases Department, Université Montpellier 1 (UM1), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital Jean Verdier [AP-HP], Laboratoire d'Ecologie Numérique et d'Ecotoxicologie, Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Infectious diseases department, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Bell Labs (BELL), Lucent Technologies, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Biotechnologie, Biocatalyse et Biorégulation (U3B), Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Centre d'épidémiologie et de santé publique des armées [Marseille] (CESPA), Service de Santé des Armées, Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Département d'infectiologie (CHU de Dijon), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), STMicroelectronics, Institut Méditerranéen d'Ecologie et de Paléoécologie (IMEP), Université Paul Cézanne - Aix-Marseille 3-Université de Provence - Aix-Marseille 1-Avignon Université (AU)-Centre National de la Recherche Scientifique (CNRS), service pharmaceutique Hôpital Edouard Herriot, Hospices Civils de Lyon, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Université de stuttgart, Université de Stuttgart, Hôpital Raymond Poincaré [AP-HP], Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Foch [Suresnes], Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier du Pays d'Aix, Nivologie (UR NIGR), Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Tourcoing, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de radiologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Universitaire de Nice (CHU Nice), Institut National de la Santé et de la Recherche Médicale (INSERM), UMR CNRS 8179, Equipe de Recherche en Physico-Chimie et Biotechnologie (ERPCB), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Geneva University Hospital (HUG), Service de chirurgie pédiatrique [Hôpital Lapeyronie-Arnaud de Villeneuve], Hôpital Lapeyronie [Montpellier] (CHU), Service de microbiologie [Saint-Louis], PRES Université Nantes Angers Le Mans (UNAM), CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuroimagerie cognitive (LCogn), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA), Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Biologie structurale des interactions entre virus et cellule hôte (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie Humaine et Moléculaire [Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Equipe 15, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université Paul Cézanne - Aix-Marseille 3-Centre National de la Recherche Scientifique (CNRS)-Avignon Université (AU)-Université de Provence - Aix-Marseille 1, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Service de virologie [CHU Pitié-Salpêtrière], INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Infection, Antimicrobiens, Modélisation, Evolution ( IAME ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Immunologie des Maladies Virales et Autoimmunes ( IMVA - U1184 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Labex_Transplantex ( Labex_Transplantex ), Centre Hospitalier Régional d'Orléans ( CHR ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Coordination Régionale de la lutte contre l'infection due au VIH ( COREVIH ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Institut Pierre Louis d'Epidémiologie et de Santé Publique ( iPLESP ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHR), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'épidémiologie et de santé publique des armées (CESPA), Service des maladies infectieuses et réanimation médicale, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, AP-HP Hôpital Raymond Poincaré [Garches], Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Besançon, Université de Franche-Comté (UFC), CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie structurale des interactions entre virus et cellule hôte, Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service des maladies infectieuses et réanimation médicale [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: Male, Microbiology (medical), Efavirenz, Genotype, Genotyping Techniques, Anti-HIV Agents, Mutation, Missense, Human immunodeficiency virus (HIV), Etravirine, Integrase inhibitor, HIV Infections, Drug resistance, Biology, medicine.disease_cause, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Men who have sex with men, chemistry.chemical_compound, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Drug Resistance, Viral, Disease Transmission, Infectious, Prevalence, medicine, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Primary HIV infection, Pharmacology (medical), Homosexuality, Male, ComputingMilieux_MISCELLANEOUS, Pharmacology, virus diseases, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Rilpivirine, HIV-1, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Resistance-associated mutations, medicine.drug
Abstract: Background Our study describes the prevalence of transmitted drug resistance (TDR) among 1318 French patients diagnosed at the time of primary HIV-1 infection (PHI) in 2007–12. Methods HIV-1 resistance-associated mutations (RAMs) were characterized using both the 2009 WHO list of mutations and the French ANRS algorithm. A genotypic susceptibility score was estimated for each first-line recommended ART combination. Results Patients were mainly MSM (72.6%). Non-B variants were identified in 33.7% of patients. The proportion of TDR was estimated as 11.7% (95% CI 10.0–13.5). The prevalences of PI-, NRTI-, first-generation NNRTI and etravirine/rilpivirine-associated RAMs were 2.5%, 5.2%, 3.9% and 3.2%, respectively. Single, dual and triple class resistance was found in 9.6%, 1.0% and 1.1% of cases, respectively. Additionally, 5/331 strains isolated in 2010–12 had integrase inhibitor (II)-related RAMs (isolated E157Q mutation in all cases). TDR was more common among MSM than in other groups (12.9% versus 8.6%, P = 0.034), and in case of B versus non-B subtype infections (13.6% versus 7.9%, P = 0.002). The proportions of fully active combinations were ≥99.2%, ≥97.3% and ≥95.3% in cases of PI-, II- and NNRTI-based regimens, respectively. In 2010–12, the proportion of fully active efavirenz-based ART was lower in cases of subtype B versus non-B infection (P = 0.021). Conclusions Compared with our previous studies, the proportion of NRTI- and first-generation NNRTI-related TDR has continued to decline in French seroconverters. However, subtype B-infected MSM could drive the spread of resistant HIV strains. Finally, we suggest preferring PI- or II- to NNRTI-based combinations to treat PHI patients.
Published: 2015
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22. Surveillance of HIV-1 primary infections in France from 2014 to 2016: toward stable resistance, but higher diversity, clustering and virulence?

Author: Visseaux, Benoit, Assoumou, Lambert, Mahjoub, Nadia, Grude, Maxime, Trabaud, Mary-Anne, Raymond, Stéphanie, Wirden, Marc, Morand-Joubert, Laurence, Roussel, Catherine, Montes, Brigitte, Bocket, Laurence, Fafi-Kremer, Samira, Amiel, Corinne, Monte, Anne De, Stefic, Karl, Pallier, Coralie, Tumiotto, Camille, Maillard, Anne, Vallet, Sophie, and Ferre, Virginie
Subjects: INFECTION, HIV, NON-nucleoside reverse transcriptase inhibitors, VIRAL load, NUCLEOSIDE reverse transcriptase inhibitors, HIV infection epidemiology, ANTI-HIV agents, HIV infections, RESEARCH, GENETICS, BIOLOGICAL evolution, SEQUENCE analysis, GENETIC mutation, RESEARCH methodology, EPIDEMIOLOGY, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies, GENOTYPES, DRUG resistance in microorganisms, MICROBIAL virulence, PHARMACODYNAMICS
Abstract: Objectives: Patients with primary HIV-1 infection (PHI) are a particular population, giving important insight about ongoing evolution of transmitted drug resistance-associated mutation (TDRAM) prevalence, HIV diversity and clustering patterns. We describe these evolutions of PHI patients diagnosed in France from 2014 to 2016.Methods: A total of 1121 PHI patients were included. TDRAMs were characterized using the 2009 Stanford list and the French ANRS algorithm. Viral subtypes and recent transmission clusters (RTCs) were also determined.Results: Patients were mainly MSM (70%) living in the Paris area (42%). TDRAMs were identified among 10.8% of patients and rose to 18.6% when including etravirine and rilpivirine TDRAMs. Prevalences of PI-, NRTI-, first-generation NNRTI-, second-generation NNRTI- and integrase inhibitor-associated TDRAMs were 2.9%, 5.0%, 4.0%, 9.4% and 5.4%, respectively. In a multivariable analysis, age >40 years and non-R5 tropic viruses were associated with a >2-fold increased risk of TDRAMs. Regarding HIV diversity, subtype B and CRF02_AG (where CRF stands for circulating recombinant form) were the two main lineages (56% and 20%, respectively). CRF02_AG was associated with higher viral load than subtype B (5.83 versus 5.40 log10 copies/mL, P=0.004). We identified 138 RTCs ranging from 2 to 14 patients and including overall 41% from the global population. Patients in RTCs were younger, more frequently born in France and more frequently MSM.Conclusions: Since 2007, the proportion of TDRAMs has been stable among French PHI patients. Non-B lineages are increasing and may be associated with more virulent CRF02_AG strains. The presence of large RTCs highlights the need for real-time cluster identification to trigger specific prevention action to achieve better control of the epidemic. [ABSTRACT FROM AUTHOR]
Published: 2020
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23. Stable prevalence of transmitted drug resistance mutations and increased circulation of non-B subtypes in antiretroviral-naive chronically HIV-infected patients in 2015/2016 in France.

Author: Assoumou, Lambert, Bocket, Laurence, Pallier, Coralie, Grude, Maxime, Ait-Namane, Rachid, Izopet, Jacques, Raymond, Stéphanie, Charpentier, Charlotte, Visseaux, Benoit, Wirden, Marc, Trabaud, Mary-Anne, Guillou-Guillemette, Hélène Le, Allaoui, Chakib, Henquell, Cécile, Krivine, Anne, Santos, Georges Dos, Delamare, Catherine, Bouvier-Alias, Magali, Montes, Brigitte, and Ferre, Virginie
Subjects: DRUG resistance, ANTIRETROVIRAL agents, HIV infections, INTEGRASE inhibitors, SAFE sex
Abstract: Objectives: We estimated the prevalence of transmitted-drug-resistance-associated mutations (TDRAMs) in antiretroviral-naive chronically HIV-1-infected patients.Patients and Methods: TDRAMs were sought in samples from 660 diagnosed HIV-1-infected individuals in 2015/2016 in 33 HIV clinical centres. Weighted analyses, considering the number of patients followed in each centre, were used to derive representative estimates of the percentage of individuals with TDRAMs. Results were compared with those of the 2010/2011 survey (n = 661) using the same methodology.Results: At inclusion, median CD4 cell counts and plasma HIV-1 RNA were 394 and 350/mm3 (P = 0.056) and 4.6 and 4.6 log10 copies/mL (P = 0.360) in the 2010/2011 survey and the 2015/2016 survey, respectively. The frequency of non-B subtypes increased from 42.9% in 2010/2011 to 54.8% in 2015/2016 (P < 0.001), including 23.4% and 30.6% of CRF02_AG (P = 0.004). The prevalence of virus with protease or reverse-transcriptase TDRAMs was 9.0% (95% CI = 6.8-11.2) in 2010/2011 and 10.8% (95% CI = 8.4-13.2) in 2015/2016 (P = 0.269). No significant increase was observed in integrase inhibitor TDRAMs (6.7% versus 9.2%, P = 0.146). Multivariable analysis showed that men infected with the B subtype were the group with the highest risk of being infected with a resistant virus compared with others (adjusted OR = 2.2, 95% CI = 1.3-3.9).Conclusions: In France in 2015/2016, the overall prevalence of TDRAMs was 10.8% and stable compared with 9.0% in the 2010/2011 survey. Non-B subtypes dramatically increased after 2010. Men infected with B subtype were the group with the highest risk of being infected with a resistant virus, highlighting the need to re-emphasize safe sex messages. [ABSTRACT FROM AUTHOR]
Published: 2019
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24. Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Author: Soulié, Cathia, Descamps, Diane, Ronique Schneider, Vé, Trabaud, Mary-Anne, Morand-Joubert, Laurence, Delaugerre, Constance, Montes, Brigitte, Barin, Francis, Ferré, Virginie, Maillard, Anne, Vallet, Sophie, Roussel, Catherine, Assoumou, Lambert, Calvez, Vincent, Flandre, Philippe, Ve, Anne-Geneviè, Jeulin, H., Guigon, A., Lagier, E., Le Guillou, H., Alloui, C., Bettinger, D., Pallier, C., Fleury, H., Reigadas, S., Bellecave, P., Recordon-Pinson, P., Payan, C., Vabret, A., Henquell, C., Mirand, A., Bouvier-Alias, M., de Rougemont, Alexis, dos Santos, G., Morand, P., Signori-Schmuck, A., Bocket, L., Rogez, S., Andre, P., Tardy, J., Tamalet, C., Delamare, C., Schvoerer, E., André-Garnier, E., Cottalorda, J., Guinard, J., Guiguon, A., Brun-Vezinet, F., Charpentier, C., Visseaux, B., Peytavin, G., Krivine, A., Si-Mohamed, A., Avettand-Fenoel, V., Marcelin, A.-G., Lambert-Niclot, S., Wirden, M., Chaix, M., Amiel, C., Schneider, V., Giraudeau, G., Brodard, V., Plantier, J., Chaplain, C., Bourlet, T., Fafi-Kremer, S., Stoll-Keller, F., Schmitt, M., Barth, H., Yerly, S., Poggi, C., Izopet, Jacques, Raymond, S., Chaillon, A., Marque-Juillet, S., Roque-Afonso, A., Haim-Boukobza, S., Grude, Maxime, Costagliola, D., Allegre, T., Schmit, J., Chennebault, J., Bouchaud, O., Magy-Bertrand, N., Delfraissy, J., Dupon, M., Morlat, P., Neau, D., Ansart, S., Jaffuel, S., Verdon, R., Jacomet, C., Levy, Y., Dominguez, S., Chavanet, P., Piroth, L., Cabié, A., Leclercq, P., Ajana, F., Cheret, A., Weinbreck, P., Cotte, L., Poizot-Martin, I., Ravaud, I., Christian, B., Truchetet, F., Grandidier, M., Reynes, J., May, T., Goehringer, F., Raffi, F., Dellamonica, P., Prazuck, T., Hocqueloux, L., Yeni, P., Landman, R., Launay, O., Weiss, L., Viard, J., Katlama, C., Simon, A., Girard, Pascal, Meynard, J., Molina, J., Pialoux, G., Hoen, B., Goeger-Sow, M., Lamaury, I., Beaucaire, G., Jaussaud, R., Rouger, C., Michelet, C., Borsa-Lebas, F., Caron, F., Khuong, M., Lucht, F., Rey, D., Calmy, A., Marchou, B., Gras, G., Greder-Belan, A., Vittecoq, D., Teicher, E., Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de bactériologie-virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre national de référence du VIH INSERM U966, Université de Tours (UT), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pontchaillou [Rennes], Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Modélisation mathématique, calcul scientifique (MMCS), Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Neuroimagerie cognitive (LCogn), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Virologie Humaine et Moléculaire [Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Faculté de médecine et pharmacie, CHU Clermont-Ferrand, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne (UB), Centre National de Référence des virus entériques [CHU de Dijon] (CNR virus entériques), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de sérologie-virologie (CHU de Dijon), Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Biologie structurale des interactions entre virus et cellule hôte (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), CHU Limoges, Laboratoire d'Informatique de Nantes Atlantique (LINA), Mines Nantes (Mines Nantes)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'électronique, optoélectronique et microsystèmes (LEOM), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Hôtel-Dieu de Nantes, Service de chirurgie pédiatrique [Hôpital Lapeyronie-Arnaud de Villeneuve], Hôpital Lapeyronie [Montpellier] (CHU), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Equipe de Recherche en Physico-Chimie et Biotechnologie (ERPCB), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Interactions et dynamique des environnements de surface (IDES), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Strasbourg], Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Environment and Sustainable Development Programme, European Commission - DG Research and Innovation, Centre Hospitalier Intercommunal de Toulon - La Seyne-sur-Mer, Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Magnétisme et Diffusion Neutronique (MDN), Modélisation et Exploration des Matériaux (MEM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier du Pays d'Aix, CHU Bordeaux [Bordeaux], Fédération des Maladies Infectieuses [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Service de médecine interne 2 et maladies infectieuses, Unité de Maladies Infectieuses et Tropicales [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Dijon, Département d'infectiologie (CHU de Dijon), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Bell Labs (BELL), Lucent Technologies, Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Service des maladies infectieuses et tropicales [CHU Nantes], CIC - Biotherapie - AP-HP (cochin - Pasteur), Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut d’Electronique et des Systèmes (IES), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Génétique Cellulaire (LGC), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Médecine interne, Maladies Infectieuses et Immunologie Clinique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), CHU Saint-Etienne, CHU Strasbourg, Geneva University Hospital (HUG), Service de Maladies Infectieuses et Tropicales [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, CHU Besançon, Université de Franche-Comté (UFC), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie structurale des interactions entre virus et cellule hôte, Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSB-INSB-Centre National de la Recherche Scientifique (CNRS), CHU Orléans, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Pitié-Salpêtrière [APHP], Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de microbiologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), University of Applied Sciences Kaiserslautern, Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Hopital l'Archet, Centre d'Information et de Soins de I'Immunodéficience Humaine (CISIH). Hôpital l'Archet 1, Hôpital l'Archet, REseau national d'Investigation clinique en VACcinologie (REIVAC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de Gestion des Essais de Produits de Santé (CeNGEPS), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Estación Experimental de Pastos y Forrajes 'Indio Hatuey', Société Ragt 2N, Service des maladies infectieuses et tropicales [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), University Hospital and University Jean Monnet, Laboratoire d'Ecologie Alpine (LECA), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Joseph Fourier - Grenoble 1 (UJF)-Université Grenoble Alpes (UGA), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Camille Jordan (ICJ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université de Tours, Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre National de la Recherche Scientifique (CNRS)-Mines Nantes (Mines Nantes)-Université de Nantes (UN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Laboratoire de virologie, Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-École Centrale de Lyon (ECL), Université de Lyon, Université Grenoble Alpes (UGA), Station de recherches sur la vache laitière, Institut National de la Recherche Agronomique (INRA), Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Hôpital Arnaud de Villeneuve, T2, Laboratoire Matériaux Optiques, Photonique et Systèmes (LMOPS), CentraleSupélec-Université de Lorraine (UL)-CentraleSupélec-Université de Lorraine (UL), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 (IEMN), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Université Polytechnique Hauts-de-France (UPHF)-Ecole Centrale de Lille-Université Polytechnique Hauts-de-France (UPHF)-Institut supérieur de l'électronique et du numérique (ISEN), and de ROUGEMONT, Alexis
Subjects: Male, Drug Resistance, HIV Infections, medicine.disease_cause, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Antiretroviral Therapy, Highly Active, Genotype, Pharmacology (medical), 030212 general & internal medicine, Viral, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ddc:616, 0303 health sciences, Mutation, medicine.diagnostic_test, Proteolytic enzymes, virus diseases, Pharmacology and Pharmaceutical Sciences, Viral Load, Middle Aged, 3. Good health, ANRS Resistance AC11 Group, Infectious Diseases, Medical Microbiology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HIV/AIDS, ARV, Female, Infection, Viral load, Microbiology (medical), Adult, Anti-HIV Agents, Antiretroviral Therapy, CSF, Microbial Sensitivity Tests, Biology, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Microbiology, Virus, resistance, 03 medical and health sciences, Clinical Research, Drug Resistance, Viral, medicine, Genetics, Humans, Highly Active, Gene, Pharmacology, 030306 microbiology, Lumbar puncture, Neurosciences, HIV, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Reverse transcriptase, Immunology, HIV-1, Antimicrobial Resistance, Nervous System Diseases
Abstract: International audience; Objectives: The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods: Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were .50 copies/mL in both compartments and bulk genotypic tests were realized. Results: On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P ¼ 0.0455) and T215Y (P ¼0.0455). Conclusions: In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performed.
Published: 2015
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25. Persistent production of an integrase-deleted HIV-1 variant with no resistance mutation and wild-type proviral DNA in a treated patient

Author: Christophe Ramière, Patrice Andre, Fabienne Venet, Mary-Anne Trabaud, Laurent Cotte, Corinne Ronfort, Guillaume Monneret, Jean-Claude Tardy, J. Saison, Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Rétrovirus et Pathologie Comparée (RPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL), Hospices Civils de Lyon [D50624], École pratique des hautes études (EPHE), and Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Viral/genetics, [SDV]Life Sciences [q-bio], Mutant, HIV Infections, Defective virus, Lopinavir, Proviruses, Leukocytes, Polymerase, Sequence Deletion, 0303 health sciences, biology, Defective Viruses, Viral Load, Resistance mutation, Mononuclear/virology, 3. Good health, Integrase, Infectious Diseases, Lamivudine, Combination, Drug Therapy, Combination, Zidovudine, Sequence Analysis, Anti-HIV Agents, HIV Infections/*drug therapy/genetics, Zidovudine/therapeutic use, Immunology, Molecular Sequence Data, Defective Viruses/genetics/*pathogenicity, Integrases/*genetics, HIV-1/*genetics, Virus, 03 medical and health sciences, Drug Therapy, Virology, Humans, Lamivudine/therapeutic use, Gene, Proviruses/genetics, 030304 developmental biology, Immune Evasion, Lopinavir/therapeutic use, Immune Evasion/genetics, Integrases, Base Sequence, 030306 microbiology, Wild type, Sequence Analysis, DNA, DNA, Molecular biology, Viral Load/drug effects, DNA, Viral, biology.protein, HIV-1, Leukocytes, Mononuclear, Anti-HIV Agents/*therapeutic use
Abstract: Supplementary Data; International audience; An HIV-infected patient presenting an unexpected viral escape under combined antiretroviral treatment is described. The virus isolated from plasma contained a large deletion in the HIV-1 integrase gene but no known resistance mutation. Nested polymerase chain reactions (PCRs) with patient virus integrase-specific primers and probes were developed and used to detect the mutant from plasma, blood, rectal biopsies, and sperm. The variant progressively emerged during a period of therapy-induced virosuppression, and persisted at a low but detectable level for at least 5 years. Surprisingly, proviral DNA from lymphocytes, rectal cells, and sperm cells was, and remained, mainly wild type. Cellular HIV RNA with the deletion was detected only once from the rectum. The origin and mechanisms underlying this so far not described production at a detectable level are largely hypothetical. This observation raised concern about the ability of defective viruses to spread.
Published: 2015
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26. Virological failure of patients on maraviroc-based antiretroviral therapy

Author: Stéphanie, Raymond, Anne, Maillard, Corinne, Amiel, Gilles, Peytavin, Mary Anne, Trabaud, Delphine, Desbois, Pantxika, Bellecave, Constance, Delaugerre, Cathia, Soulie, Anne Geneviève, Marcelin, Diane, Descamps, Jacques, Izopet, J, Izopet, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pharmacocinétique clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de microbiologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Virologie, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Microbiology (medical), Adult, Male, resistance to maraviroc, viruses, [SDV]Life Sciences [q-bio], Population, Drug Resistance, Antiretroviral Therapy, HIV Infections, Drug resistance, Biology, Maraviroc, chemistry.chemical_compound, Cyclohexanes, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, HIV tropism, Humans, Pharmacology (medical), Highly Active, Viral, Treatment Failure, education, Genotyping, Tropism, Aged, Retrospective Studies, Pharmacology, CXCR4, education.field_of_study, HIV-1 tropism determination, phenotypic assay, Middle Aged, Triazoles, Viral Load, Virology, 3. Good health, Viral Tropism, Infectious Diseases, chemistry, Anti-Retroviral Agents, Immunology, Tissue tropism, HIV-1, entry, Female, Viral load
Abstract: Objectives Virological failure (VF) in patients on maraviroc-based treatment has been associated with altered HIV tropism and resistance to maraviroc. This multicentre study aimed to characterize VF in patients treated with maraviroc. Methods We analysed 27 patients whose treatment failed between 2008 and 2011. They had been screened for HIV tropism before maraviroc initiation using population-based V3 genotyping. HIV-1 tropism and resistance of R5 viruses to maraviroc at VF and at baseline were determined retrospectively using an ultrasensitive recombinant virus assay (RVA). Results Viruses from 27 patients given maraviroc on the basis of the R5 genotype were characterized at the time of treatment failure. The RVA indicated that 12 patients harboured CXCR4-using viruses and 15 (56%) had pure R5 viruses at failure. One-third of those harbouring CXCR4-using viruses (4/12) were infected with R5X4/X4 viruses according to the RVA before maraviroc initiation. We analysed the phenotypic resistance to maraviroc of four patients harbouring R5 viruses at failure; two harboured viruses whose maximum percentage inhibition was reduced by 65%–90%, while the other two were infected with susceptible viruses. All patients had effective concentrations of drugs. Conclusions Half of the maraviroc-treated patients who experienced VF harboured CXCR4-using viruses at failure, one-third of them were detected by a phenotypic method before maraviroc initiation. Phenotypic assessment of R5 virus resistance to CCR5 antagonists at failure could help optimize antiretroviral therapy.
Published: 2014
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27. Correlation between antiretroviral resistance mutations, biological parameters, and clinical evolution in zidovudine-treated patients infected with human immunodeficiency virus type 1

Author: F. Bissuel, Mary-Anne Trabaud, C. Trepo, E. Deruelle, P. Rougier, K. Leriche-Guérin, and L. Cotte
Subjects: Adult, Male, Microbiology (medical), Anti-HIV Agents, Drug Resistance, HIV Core Protein p24, HIV Infections, medicine.disease_cause, Polymerase Chain Reaction, Virus, Zidovudine, immune system diseases, Immunopathology, medicine, Humans, Sida, Analysis of Variance, Mutation, biology, virus diseases, General Medicine, biology.organism_classification, Virology, HIV Reverse Transcriptase, Reverse transcriptase, CD4 Lymphocyte Count, Infectious Diseases, Immunology, Disease Progression, HIV-1, RNA, Viral, Female, Viral disease, Viral load, medicine.drug
Abstract: To evaluate the correlation between zidovudine (ZDV) resistance mutations of human immunodeficiency virus type 1 (HIV-1), biological parameters, and clinical evolution, 111 HIV-1-infected patients treated with ZDV were studied. Specific mutations at codons 70, 215, and 41 in the HIV-1 reverse transcriptase coding region conferring resistance to ZDV were detected using a selective polymerase chain reaction. The appearance of ZDV resistance mutations was significantly correlated with baseline clinical stage, CD4+ cell count, and viral load, but not with duration of ZDV therapy or p24 antigen level. In univariate analysis, results showed a prognostic role of mutations at codons 215 and 41 for clinical progression to the acquired immune deficiency syndrome (AIDS) or death. In multivariate analysis after controlling for viral load, CD4+ cell count, and clinical stage, the presence of the mutation at codon 215 (but not at codon 41) remained an independent predictor of subsequent clinical evolution.
Published: 1997
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28. A cohort study of treatment-experienced HIV-1-infected patients treated with raltegravir: factors associated with virological response and mutations selected at failure

Author: Marcelin, Anne-Geneviève, Delaugerre, Constance, Beaudoux, Céline, Descamps, Diane, Morand-Joubert, Laurence, Amiel, Corinne, Schneider, Veronique, Ferre, Virginie, Izopet, Jacques, Si-Mohamed, Ali, Maillard, Anne, Henquell, Cécile, Desbois, Delphine, Lazrek, Mouna, Signori-Schmuck, Anne, Rogez, Sylvie, Yerly, Sabine, Trabaud, Mary-Anne, Plantier, Jean-Christophe, Fourati, Slim, Houssaini, Allal, Masquelier, Bernard, Calvez, Vincent, Flandre, Philippe, Michelet, Christian, Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de bactériologie-virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Virologie [Purpan], CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, Laboratoire de virologie [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU), Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), ANRS AC11 Resistance Group, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Oncology, Male, Enfuvirtide, Etravirine, Pyrrolidinones/therapeutic use, HIV Infections, Integrase, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, Medicine, Pharmacology (medical), 030212 general & internal medicine, Treatment Failure, ddc:616, 0303 health sciences, biology, Response, General Medicine, Viral Load, Resistance mutation, Pyrrolidinones, Antiretroviral Therapy, Highly Active/methods, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, RNA, Viral, Female, Viral load, Mutations, medicine.drug, Microbiology (medical), medicine.medical_specialty, animal structures, Inhibitor, Efficacy, Anti-HIV Agents, Mutation, Missense, 03 medical and health sciences, Internal medicine, Raltegravir Potassium, Drug Resistance, Viral, Humans, RNA, Viral/blood, HIV Infections/drug therapy/virology, Darunavir, Maraviroc, 030306 microbiology, business.industry, Raltegravir, Virology, HIV-1/genetics/isolation & purification, CD4 Lymphocyte Count, chemistry, Anti-HIV Agents/therapeutic use, biology.protein, HIV-1, business
Abstract: International audience; This study aimed to identify factors associated with virological response (VR) to raltegravir (RAL)-containing regimens in 468 treatment-experienced but integrase inhibitor-naive HIV-1 patients receiving a RAL-containing regimen. VR was defined at Month 6 (M6) as HIV-1 RNA viral load (VL) 50 copies/mL at M6, integrase mutations selected were characterised. Median baseline VL was 4.2 log(10)copies/mL (IQR 3.3-4.9 log(10) copies/mL) and CD4 count was 219 cells/mm(3) (IQR 96-368 cells/mm(3)). At M6, 71% of patients were responders. In multivariate analysis, baseline VL and CD4 count and ≥ 2 new antiretrovirals among darunavir, etravirine, maraviroc and enfuvirtide were associated with VR to RAL. Neither HIV-1 subtype nor baseline integrase polymorphisms were associated with VR to RAL. Among 63 failing patients at M6, selection of ≥ 1 change in the integrase gene was observed in 49 (77.8%), and 27/63 (42.9%) were considered as RAL-associated resistance mutations. Factors independently associated with the occurrence of ≥ 1 RAL-associated resistance mutation were VL at failure >3 log(10) and having no new drugs associated with RAL. RAL showed great potency in treatment-experienced patients. The number of new drugs associated with RAL was an important factor associated with VR. HIV-1 subtype and baseline integrase polymorphisms do not influence the RAL VR.
Published: 2013
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29. HIV-1 integrase variability and relationship with drug resistance in antiretroviral-naive and -experienced patients with different HIV-1 subtypes

Author: S, Reigadas, A G, Marcelin, A, Houssaïni, S, Yerly, D, Descamps, J C, Plantier, A, Ruffault, C, Amiel, M A, Trabaud, Philippe, Flandre, H, Fleury, B, Masquelier, S, Marque-Juillet, Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Unité de Rétrovirologie, Hôpital Pontchaillou, Infectious Diseases Department, Université Montpellier 1 (UM1), Virology Laboratory, Bordeaux University Hospital, Bordeaux, France, Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Service de virologie [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: Microbiology (medical), Anti-HIV Agents, HIV Integrase/genetics, Molecular Sequence Data, Human immunodeficiency virus (HIV), Mutation, Missense, HIV Infections, Drug resistance, HIV Integrase, Bioinformatics, medicine.disease_cause, 03 medical and health sciences, Anti-HIV Agents/pharmacology, Drug Resistance, Viral, medicine, Antiretroviral naive, Humans, Pharmacology (medical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, ddc:616, HIV-1/drug effects/genetics/isolation & purification, Pharmacology, 0303 health sciences, biology, Group study, 030306 microbiology, Genetic Variation, Sequence Analysis, DNA, Hiv subtype, Virology, 3. Good health, Integrase, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Hiv 1 integrase, biology.protein, HIV-1, HIV Infections/virology
Abstract: H-932. American Society for Microbiology, Washington, DC, USA. 10 Nouhin J, Donchai T, Hoang KT et al. Natural polymorphisms of HIV-1 CRF01_AE integrase coding region in ARV-naive individuals in Cambodia, Thailand and Vietnam: an ANRS AC12 working group study. Infect Genet Evol 2011; 11: 38–43. 11 Wainberg MA, Brenner BG. Role of HIV subtype diversity in the development of resistance to antiviral drugs. Viruses 2010; 2: 2493–508. Research letter
Published: 2013

30. Low-level viremia is associated with non-B subtypes in patients infected with HIV with virological success following HAART introduction

Author: Mary-Anne Trabaud, T. Ferry, P. André, Jean-Claude Tardy, J. Saison, René Ecochard, Christian Chidiac, Thomas Perpoint, Caroline Scholtes, Vinca Icard, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Anti-HIV Agents, [SDV]Life Sciences [q-bio], HIV Infections, Viremia, Biology, 03 medical and health sciences, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, Virology, medicine, Humans, In patient, Protease inhibitor (pharmacology), Prospective Studies, 030212 general & internal medicine, Prospective cohort study, 0303 health sciences, Univariate analysis, 030306 microbiology, Proportional hazards model, virus diseases, Middle Aged, Viral Load, medicine.disease, Virus Latency, 3. Good health, Regimen, Infectious Diseases, HIV-1, RNA, Viral, Female, Viral load
Abstract: This prospective study aimed to determine factors associated with detection of very low-level viremia in patients infected with HIV-1 with virological success following HAART introduction. Fifty-seven patients, mostly (n = 51, 89%) treated with a protease inhibitor-based regimen, were included and followed for 2 years. Viral loads were monitored by Abbott m2000 RealTime HIV-1. Patients were classified as (i) HIV-RNA-negative if viral loads remained strictly undetectable (0 copies/ml), or (ii) HIV-RNA-positive if at least one HIV-1 RNA could be detected in 1–49 copies/ml during follow-up. At month 24, 44 patients (77%) were in the HIV-RNA-positive group, whereas 13 (23%) remained without very low-level viremia. Univariate analysis, Kaplan–Meier curves and the Cox proportional hazard model revealed that B subtype was the only predictor of belonging to the HIV-RNA-negative group (HR 3.98; 95% CI 1.08–14.7). This association needs to be confirmed. Further study of the reservoir and the mechanisms of viral latency according to HIV-subtype will also be necessary to develop new therapeutic strategies and eradicate HIV infection. J. Med. Virol. 85: 953–958, 2013. © 2013 Wiley Periodicals, Inc.
Published: 2013
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31. In vitro studies reveal that different modes of initiation on HIV-1 mRNA have different levels of requirement for eukaryotic initiation factor 4F

Author: de Breyne, Sylvain, Chamond, Nathalie, Décimo, Didier, Trabaud, Mary-Anne, André, Patrice, Sargueil, Bruno, Ohlmann, Théophile, Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon, Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), and École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Genes, Viral, MESH: Humans, Genes, Viral, MESH: Codon, [SDV]Life Sciences [q-bio], In Vitro Techniques, MESH: Eukaryotic Initiation Factor-4F, MESH: HIV-1, Eukaryotic Initiation Factor-4F, Protein Biosynthesis, MESH: Protein Biosynthesis, HIV-1, Humans, MESH: 5' Untranslated Regions, RNA, Messenger, 5' Untranslated Regions, Codon, MESH: RNA, Messenger
Abstract: International audience; Expression of the two isoforms p55 and p40 of HIV-1 Gag proteins relies on distinct translation initiation mechanisms, a cap-dependent initiation and two internal ribosome entry sites (IRESs). The regulation of these processes is complex and remains poorly understood. This study was focused on the influence of the 5'-UTR and on the requirement for the eukaryotic initiation factor (eIF)4F complex components. By using an in vitro system, we showed substantial involvement of the 5'-UTR in the control of p55 expression. This highly structured 5'-UTR requires the eIF4F complex, especially RNA helicase eIF4A, which mediates initiation at the authentic AUG codon. In addition, the 5'-UTR regulates expression in an RNA concentration-dependent manner, with a high concentration of RNA triggering specific reduction of full-length Gag p55 production. HIV-1 genomic RNA also has the ability to use a strong IRES element located in the gag coding region. We show that this mechanism is particularly efficient, and that activity of this IRES is only poorly dependent on RNA helicase eIF4A when the viral 5'-UTR is removed. HIV-1 genomic mRNA exhibits in vitro translational features that allow the expression of Gag p55 protein by different mechanisms that involve different requirements for eIF4E, eIF4G, and eIF4A. This suggests that HIV-1 could adapt to its mode of translation according to the availability of the initiation factors in the infected cell.
Published: 2012
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32. Discordance in HIV-1 co-receptor use prediction by different genotypic algorithms and phenotype assay: intermediate profile in relation to concordant predictions

Author: Caroline Scholtes, Jean Claude Tardy, Joseph Koffi, Vinca Icard, Djamila Makhloufi, Thomas Perpoint, Laurent Cotte, Mary-Anne Trabaud, and Patrice Andre
Subjects: Male, Receptors, CXCR4, Genotype, Receptors, CCR5, Concordance, Human immunodeficiency virus (HIV), HIV Infections, Biology, medicine.disease_cause, Virology, medicine, Humans, Tropism, Genetics, Plasma samples, Computational Biology, Phenotype, Predictive value, Viral Tropism, Infectious Diseases, HIV-1, Female, Algorithm, Algorithms
Abstract: Concordant and discordant genotypic predictions of HIV-1 co-receptor tropism were analyzed. V3 region was sequenced from plasma samples of patients screened for R5 tropism by the Trofile® assay, before CCR5 antagonist prescription. Ten tools including geno2pheno, PSSM, an “11/25” and “net charge” rule, and other published algorithms were used. Patients were grouped according to concordance or discordance between tools and Trofile® result. Trofile® tropism reports from 50 patient samples were R5 in 38 and Dual/Mixed (DM) in 12. Prediction with the genotypic tools were concordant for 23 R5 samples, and discordant for the 15 other ones. From Trofile® DM strains were concordant in 6 and discordant in 6. V3 sequences were not clearly distinct between R5 and DM strains, except a greater diversity in the later. Discordances were found with any tool or combination of them, so that no one can be proposed as better than the others. Predictive values of each algorithm were similar and rather good (efficacy ranged from 74% to 84%), but the rate of non-confirmed prediction is greater when compelling the results of all tools with each individual sample. The mean of quantitative values obtained with one tool when another tool give the opposite prediction were different from those obtained when all tools agree with that prediction. The two discordant groups were often not distinguishable from each other. These results suggest that viruses giving discordant prediction with bioinformatic tools could be functionally distinct and/or in a different evolutionary state compared to those with concordant prediction. J. Med. Virol. 84:402–413, 2012. © 2011 Wiley Periodicals, Inc.
Published: 2012

33. Improved V3 genotyping with duplicate PCR amplification for determining HIV-1 tropism

Author: Hervé Fleury, Bernard Masquelier, P. André, Anne Maillard, Florence Nicot, Stéphanie Raymond, Jacques Izopet, Ali Si-Mohammed, Anne-Geneviève Marcelin, B. Masquelier, Françoise Brun-Vézinet, Michel Segondy, Diane Descamps, Jean-Claude Tardy, Muriel Macé, P. Recordon-Pinson, F. Nicot, V. Calvez, Mary-Anne Trabaud, A G Marcelin, Corinne Amiel, Adrien Saliou, Véronique Schneider, Catherine Tamalet, Pierre Delobel, Brigitte Montes, Mouna Lazrek, Laurence Morand-Joubert, Astrid Vabret, Coralie Pallier, Annick Ruffault, Patricia Recordon-Pinson, C Charpentier, Vincent Calvez, Cathia Soulié, Delphine Desbois, Virginie Ferré, Jacqueline Cottalorda, F. Flandre, S. Raymond, P. Delobel, E. Dussaix, Philippe Flandre, J. Izopet, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Virology Laboratory, Hospital, Service de microbiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Mathématiques Pures et Appliquées (UMPA-ENSL), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Virologie, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Service des Maladies Infectieuses et Tropicales, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), and VIROLOGIE
Subjects: Microbiology (medical), Adult, Male, Receptors, CXCR4, Genotype, education, HIV Infections, Biology, MESH: Phenotype, MESH: Receptors, CXCR4, law.invention, MESH: Genotype, MESH: HIV-1, 03 medical and health sciences, 0302 clinical medicine, law, MESH: Reverse Transcriptase Polymerase Chain Reaction, HIV tropism, Humans, Pharmacology (medical), 030212 general & internal medicine, Genotyping, Tropism, Polymerase chain reaction, Pharmacology, 0303 health sciences, MESH: Humans, MESH: Middle Aged, 030306 microbiology, Reverse Transcriptase Polymerase Chain Reaction, MESH: Adult, MESH: HIV Infections, Amplicon, Middle Aged, Virology, Molecular biology, MESH: Male, 3. Good health, Viral Tropism, Infectious Diseases, Phenotype, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Tissue tropism, HIV-1, Female, MESH: Female, MESH: Viral Tropism, Trofile assay
Abstract: International audience; OBJECTIVES: To determine whether genotyping of HIV-1 by duplicate PCR amplification of the region encoding the V3 loop is more sensitive than single PCR for detecting CXCR4-using viruses. PATIENTS AND METHODS: The V3 genotypes of the HIV-1 infecting 152 patients enrolled in the multicentre GenoTropism ANRS study were determined by all the participating laboratories using a single PCR and V3 bulk sequencing. In parallel, one laboratory determined the V3 genotype using duplicate PCR and bulk sequencing of pooled amplicons. HIV tropism was predicted with the geno2pheno10 algorithm. The phenotypes of all samples were determined with the Trofile assay and the Toulouse tropism test (TTT) recombinant virus assay. RESULTS: Geno2pheno10 was 56.8% sensitive and 75.9% specific when compared with the Trofile assay for detecting CXCR4-using viruses after a single PCR. Duplicate amplification and bulk sequencing of the pooled PCR amplicons increased the sensitivity to 68.2% and specificity to 79.6%. Geno2pheno10 was 64.1% sensitive and 77.0% specific when compared with the TTT assay for detecting CXCR4-using viruses after a single PCR. Duplicate amplification and sequencing of the pooled PCR amplicons increased sensitivity to 76.9% and specificity to 80.5%. CONCLUSIONS: The genotypic determination of HIV-1 tropism can be improved by duplicate amplifications and sequencing the pooled PCR products. This is a good compromise between improved sensitivity and reasonable cost for the genotype-based determination of tropism.
Published: 2011
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34. HIV-1 Load Comparison Using Four Commercial Real-Time Assays

Author: Thomas Bourlet, Patrice Andre, Henia Saoudin, Vinca Icard, Laurent Roche, Mary-Anne Trabaud, René Ecochard, Anne Signori-Schmuck, Jean-Claude Tardy, Bruno Pozzetto, Patrice Morand, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Microbiology (medical), medicine.medical_specialty, Cobas taqman, [SDV]Life Sciences [q-bio], HIV Infections, 03 medical and health sciences, 0302 clinical medicine, Virology, Internal medicine, Antiretroviral treatment, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, HIV-1 Load, 0303 health sciences, biology, 030306 microbiology, Disease progression, Viral Load, biology.organism_classification, Hiv seropositivity, 3. Good health, Lentivirus, HIV-1, RNA, Viral, Reagent Kits, Diagnostic, Viral load
Abstract: The HIV-1 RNA viral load is commonly used for the monitoring of disease progression and antiretroviral treatment of HIV-1-infected patients. Since the misestimating of values could lead to inappropriate therapeutical management, the comparative performances, especially the ability to span the genetic diversity of HIV-1, of available automated real-time assays need to be evaluated. We conducted a prospective study with 74 consenting patients enrolled between March 2007 and November 2008. A blood sample was obtained at the time of diagnosis of HIV seropositivity and blindly tested for HIV-1 RNA by at least 4 commercial tests: the Abbott m 2000 RealTi m e HIV-1, bioMérieux NucliSens EasyQ HIV-1, version 1.2 (v1.2), and Cobas AmpliPrep/Cobas TaqMan (CAP/CTM) v1.0 and v2.0 assays. The means of difference were null between CAP/CTM v2.0 and Abbott for CRF02_AG subtypes but positive in favor of CAP/CTM v2.0 for genotype B and negative in favor of NucliSens for all genotypes. The standard deviation (SD) of difference ranged from 0.3 to 0.59, depending on the considered couples of assays. Reliabilities of these four tests, appreciated by the standard deviation of difference between the measurement and the estimated “true” viral load and by the coefficient of reliability, were significantly different ( P < 10 −4 ) among each other. Significant differences were also observed within each group of HIV-1 genotype. The global disparity was higher for CRF02_AG than for B subtypes. This study indicates a risk of viral load misestimating or discrepancies between techniques, depending on the HIV-1 subtype, and speaks in favor of using the same assay for the monitoring of HIV-1-infected patients.
Published: 2011
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35. Proficiency of transient elastography compared to liver biopsy for the assessment of fibrosis in HIV/HBV-coinfected patients

Author: P, Miailhes, P, Pradat, M, Chevallier, K, Lacombe, F, Bailly, L, Cotte, M-A, Trabaud, A, Boibieux, J, Bottero, C, Trepo, F, Zoulim, Equipe 15, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Equipe 16, Institut de Physique Nucléaire de Lyon (IPNL), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Institut de recherche en astrophysique et planétologie (IRAP), Institut national des sciences de l'Univers (INSU - CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Liver Cirrhosis, Male, Hepatitis B virus, Biopsy, HIV Infections, MESH: Algorithms, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Elasticity Imaging Techniques, MESH: HIV-1, Young Adult, MESH: Biopsy, Humans, MESH: Middle Aged, MESH: Humans, MESH: Hepatitis B, MESH: Adult, MESH: HIV Infections, Middle Aged, Hepatitis B, MESH: Male, MESH: Hepatitis B virus, Liver, MESH: Young Adult, HIV-1, Elasticity Imaging Techniques, Female, MESH: Liver Cirrhosis, MESH: Female, Algorithms, MESH: Liver
Abstract: International audience; Transient elastography (TE) is a noninvasive technique to evaluate liver fibrosis. We compared the performance of TE with liver biopsy (LB) in patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection. Patients prospectively underwent TE and LB. The diagnosis accuracy of TE was calculated using receiver operating characteristic (ROC) curves for different stages of fibrosis, and optimal cut-off values were defined. A sequential algorithm combining TE with biochemical score (Fibrotest) is proposed. Fifty-seven patients had both TE and LB (median time: 3 days) and two with proven cirrhosis, only TE. Forty-six (78%) were under antiretroviral therapy with anti-HBV drugs in 98%, and 19 (32%) had elevated alanine aminotransferase (ALT). A significant correlation was observed between liver stiffness measurement (LSM) and METAVIR fibrosis stages (P < 0.0001). Patients with elevated ALT tended to have higher LSM than those with normal ALT. The areas under the ROC curves were 0.85 for significant fibrosis (≥ F2), 0.92 for advanced fibrosis (≥ F3) and 0.96 for cirrhosis. Using a cut-off of 5.9 kPa for F ≥ 2 and 7.6 kPa for F ≥ 3, the diagnosis accuracy was 83% and 86%, respectively. With an algorithm combining TE and Fibrotest, 97% of patients were well classified for significant fibrosis. Using this algorithm, the need for LB can be reduced by 67%. In HIV/HBV-coinfected patients, most of them with normal ALT under antiretroviral treatment including HBV active drugs, TE was proficient in discriminating moderate to severe fibrosis from minimal liver disease.
Published: 2011
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36. Measuring human immunodeficiency virus type 1 RNA loads in dried blood spot specimens using NucliSENS EasyQ HIV-1 v2.0

Author: Patrice Andre, Lieke Bertens, Veronique Ligeon, André Verhoeven, Tom Oosterlaken, Jacques de Jong, Mary Anne Trabaud, and Peter van Deursen
Subjects: Veterinary medicine, Time Factors, Human immunodeficiency virus (HIV), Diagnostic Specificity, Clinical state, Biology, medicine.disease_cause, Sensitivity and Specificity, Specimen Handling, Virology, medicine, Animals, Humans, Desiccation, Self-Sustained Sequence Replication, Detection limit, Temperature, Humidity, Plasma levels, Viral Load, Dried blood spot, Nuclisens easyq, Infectious Diseases, Blood, HIV-1, RNA, Viral, Viral load
Abstract: Background HIV-1 RNA plasma level is a key parameter for anti-viral treatment monitoring in HIV-1 infected individuals. Plasma stability and accurate measurement of clinical state is at risk when transporting from remote areas. Dried blood spot (DBS) testing can reduce this risk. Objectives Determine the performance of NucliSENS EasyQ HIV-1 v2.0 for DBS. Study design 100 HIV-1 negative, and 129 HIV-1 spiked blood specimens (2180 copies/ml) were used for diagnostic specificity and system robustness. Analytical performance was tested in the range 50–85,000,000 copies/ml. Clinical reactivity was measured with specimens obtained from 224 HIV-1 infected individuals. HIV-1 RNA stability was analyzed after applying several different storage conditions. Results Diagnostic specificity was 100% and system robustness was demonstrated by 100% detection rate without invalids. Limit of detection (95% detection rate) was 800 copies/ml. Linear results were obtained over the whole range tested. For clinical specimens, percentage positive results were comparable for DBS (57%) and plasma (58%). DBS quantification was on average 0.36 log 10 lower as compared to plasma. Specimen stability was demonstrated for 1 week at 55 °C/60% humidity, 3 weeks at 37 °C/80% humidity, 9 weeks at 37 °C/40% humidity, 3 months at −20 °C/70% humidity, 3 weeks at 4 °C/100% humidity, 9 months at room temperature (15–30 °C), and 9 weeks shipment simulation. Conclusion Results obtained fully support the use of DBS for the NucliSENS EasyQ HIV-1 v2.0 assay. These findings are especially of importance in cases that plasma stability is currently at risk due to for example, long transport routes from remote areas under less controlled conditions.
Published: 2009

37. Prediction of the virological response to etravirine in clinical practice: Comparison of three genotype algorithms

Author: Christian Trepo, Mary-Anne Trabaud, Jean-Claude Tardy, Patrick Miailhes, Laurent Cotte, Corinne Brochier, René-Pierre Gilibert, and Patrice Andre
Subjects: Genotype, Anti-HIV Agents, Concordance, Etravirine, HIV Infections, Drug resistance, Biology, Predictive Value of Tests, Virology, Databases, Genetic, Drug Resistance, Viral, Nitriles, medicine, Humans, Sida, Reverse-transcriptase inhibitor, biology.organism_classification, Reverse transcriptase, HIV Reverse Transcriptase, Pyridazines, Infectious Diseases, Pyrimidines, Treatment Outcome, Lentivirus, Mutation, HIV-1, Reverse Transcriptase Inhibitors, Algorithm, Algorithms, medicine.drug
Abstract: The current Agence Nationale de Recherche sur le SIDA (ANRS)/International AIDS Society (IAS) algorithm predicts resistance to etravirine for viruses harboring ≥3 mutations from a list of 13 reverse transcriptase (RT) mutations. Two weighted algorithms, best correlated with fold changes to etravirine, have been described recently. A retrospective virological analysis of a major French city HIV sequences database was undertaken to assess the proportion of etravirine resistant viruses according to these three algorithms and the correlations between them. Two thousand six hundred eighty RT sequences were analyzed, including 749 from naive patients and 926 from patients previously treated with non-nucleoside reverse transcriptase inhibitor (NNRTI). Combinations of mutations associated with etravirine resistance according to the three algorithms were found in 0%, 2.3%, and 3.6% of naive patients, and in 2.4%, 20.4%, and 19.3% of patients previously treated with NNRTIs. Concordance between the algorithms was weak (2 × 2 Kendall's tau: 0.787, 0.395, and 0.584). Most of the discordance was due to the differential weights attributed to Y181C/V, L100I, and K101P in the two weighted algorithms. It is concluded that the current ANRS/ IAS algorithm probably underestimates the proportion of viruses partially resistant to etravirine in NNRTI-experienced patients. Improvements in algorithms are needed to take into account the partial resistance associated with some mutation patterns, and should include either additional mutations to the current list and/or differential weights for specific mutations. Surveys of naive patients should be conducted to estimate the risk of primary resistance to etravirine in a minority of cases. J. Med. Virol. 81:672–677, 2009 © 2009 Wiley-Liss, Inc.
Published: 2009

38. Variants with different mutation patterns persist in the quasispecies of enfuvirtide-resistant HIV-1 population during and after treatment in vivo

Author: Jean Louis Labernardière, Laurent Cotte, Patrice Andre, Jean-Claude Tardy, Mary Anne Trabaud, Sophie Lebel-Binay, Christian Trepo, and Vinca Icard
Subjects: Enfuvirtide, Population, Molecular Sequence Data, HIV Infections, Viral quasispecies, Biology, Recombinant virus, Gp41, medicine.disease_cause, Genetic variation, Genotype, Drug Resistance, Viral, medicine, Humans, Pharmacology (medical), Amino Acid Sequence, Treatment Failure, education, Phylogeny, Retrospective Studies, Genetics, education.field_of_study, Mutation, Genetic Variation, Viral Load, Virology, HIV Envelope Protein gp41, Peptide Fragments, Protein Structure, Tertiary, Infectious Diseases, HIV-1, Sequence Alignment, medicine.drug
Abstract: Background: Genotypic and phenotypic resistance in 11 HIV-1-infected patients receiving enfuvirtide (ENF), as part of a salvage regimen, has been evaluated. Methods: Resistance mutations were detected by sequencing the gp41 ectodomain from plasma samples. During treatment, longitudinal samples from 1 patient were sequenced after limiting dilution of complementary DNA to isolate single genomes. Phenotypic resistance was evaluated with a new recombinant virus assay (PHENO-SCRIPT; VIRalliance, Paris, France), allowing the determination of coreceptor use. Results: All patients experienced ENF failure. One to 4 mutations in the 36-to-45 gp41 region appeared during ENF therapy in all patients and disappeared after ENF removal. Mixtures of wild type and mutants unexpectedly persisted under ENF treatment, however, despite continued replication, leading to discordant results between genotypic and phenotypic data. Sequencing of isolated genomes from 1 patient confirmed that a wild-type first heptad repeat region (HR1) region was still present at the end of therapy. Several mutated variants coexisted at different time points, despite a tendency toward quasispecies reduction with time. Conclusion: Individual variability of the mutation pattern and persistence of strains without mutation in the region mainly targeted by ENF resistance probably reflect the fact that resistance to ENF may rely on regions of gp41 or gp120 other than residues 36 to 45.
Published: 2007

39. Comparison of HIV-1 drug-resistance genotyping by ultra-deep sequencing and sanger sequencing using clinical samples.

Author: Trabaud, Mary‐Anne, Icard, Vinca, Ramière, Christophe, Tardy, Jean‐Claude, Scholtes, Caroline, and André, Patrice
Abstract: Sanger population sequencing (SPS) is the reference technique to monitor HIV-1-infected patients' therapy. Ultra-deep sequencing (UDS), which allows quantitative detection of drug resistance mutations, may be an alternative method. The study aimed to compare reproducibility and predictions of UDS versus SPS in a routine setting. A control containing low-abundance variants was repeatedly tested and clinical plasma samples from 100 patients were prospectively assayed by SPS and UDS using the Roche 454 system. Complete analysis by UDS was available for 88% of samples with various viral loads and subtypes. Comparison of detection thresholds found that SPS sensitivity was variable. Variations found by UDS between 5% to >20% were detected by SPS in 25% to more than 80% of samples. At the 5% cut-off, disagreements were rare and in most cases UDS detected an additional protease secondary mutation, suggesting a possible resistance to a protease inhibitor according to the 2015 ANRS algorithm. Mutations found on reverse transcriptase by only UDS were often explained by previous therapy. UDS with a variant detection threshold at 5% might allow therapy management with minimal differences compared to population sequencing while providing additional information for further determination of pertinent cutoff values for specific resistance mutations. [ABSTRACT FROM AUTHOR]
Published: 2017
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40. Failure and success of HIV tests for the prevention of HIV-1 transmission by blood and tissue donations

Author: Fatiha, Najioullah, Valérie, Barlet, Philippe, Renaudier, Cathy, Guitton, Philippe, Crova, Jean-Claude, Guérin, Dominique, Peyramond, Marie-Anne, Trabaud, Nicole, Coudurier, Jean-Claude, Tardy, and Patrice, André
Subjects: Base Sequence, Genes, Viral, Molecular Sequence Data, HIV Core Protein p24, Transplants, Blood Donors, HIV Infections, Antibodies, Viral, HIV Reverse Transcriptase, Tissue Donors, Blood, HIV Protease, Sequence Homology, Nucleic Acid, HIV-1, Humans, RNA, Viral, Female, Sequence Alignment, Aged
Abstract: French blood banks recently implemented nucleic acid testing (NAT) of all blood donations to reduce the risk of HIV transmission during the pre-seroconversion period. For tissue donation, HIV infection screening relies on HIV p24 antigen and anti-HIV-1 and 2 antibody detection. In this report, two related cases of infectious donations are described from a cornea donor during the preseroconversion window who was infected by an HIV antibody and NAT negative blood donor. After investigation, the blood donor was found to be herself in the preseroconversion window. Two months after donation, she was found to be HIV positive. The residual risk of HIV infectious blood donations since NAT has been introduced is estimated to be lower than one out of 2.5 millions. Individual NAT instead of minipool testing would not increase significantly the blood transfusion safety. In contrast, introduction of NAT should be considered to increase tissue donation safety as soon as such screening will be possible technically.
Published: 2004

41. Prevalence of primary resistance to zidovudine and lamivudine in drug-naive human immunodeficiency virus type-1 infected patients: high proportion of reverse transcriptase codon 215 mutant in circulating lymphocytes and free virus

Author: Christian Trepo, Jill Detmer, Karine Leriche‐Guerin, Jacques Ritter, Mary-Anne Trabaud, Corinne Régis, Isabelle Bordes, Janice A. Kolberg, and Laurent Cotte
Subjects: Anti-HIV Agents, viruses, Mutant, HIV Infections, Biology, Polymerase Chain Reaction, Virus, Zidovudine, Proviruses, Virology, medicine, Humans, Lymphocytes, Codon, Lamivudine, Nucleic Acid Hybridization, Drug Resistance, Microbial, biochemical phenomena, metabolism, and nutrition, Provirus, Viral Load, Resistance mutation, Reverse transcriptase, HIV Reverse Transcriptase, Infectious Diseases, DNA, Viral, HIV-1, RNA, Viral, Reverse Transcriptase Inhibitors, Viral load, medicine.drug
Abstract: The presence of primary zidovudine (AZT)-resistance (mutation T215Y/F) or lamivudine (3TC)-resistance (mutation M184V) was evaluated in 90 drug-naive patients infected with human immunodeficiency virus type-1 (HIV-1) between 1987 and 1997. The proportion of mutant strains in proviral samples or plasma viral samples was determined using a differential hybridization assay. Mutation T215Y/F was found in five (5.6%) patients infected between 1994 and 1997, whereas none of these patients harbored the mutation M184V. The T215Y/F mutation was present in the virus and/or provirus and persisted for at least two years. In one patient, the mutant provirus was associated with only wild-type free virus. Four of these patients were followed, and two were treated subsequently to a regimen containing AZT but with low response. The persistence of primary resistance mutations might depend on the proportion of these mutations at the time of infection, although mutant provirus might not give rise to replicating variants.
Published: 2000

42. Can virostatic chemotherapy and/or adoptive allogeneic immunotherapy eradicate in vivo Friend's virus infection?

Author: E. Chenu, C. Bourut, Mathé G, and M Trabaud
Subjects: viruses, medicine.medical_treatment, Biology, Virus, Mice, chemistry.chemical_compound, Drug Therapy, In vivo, hemic and lymphatic diseases, medicine, Animals, Pharmacology, Elliptinium, Chemotherapy, Leukemia, Experimental, General Medicine, Immunotherapy, Virology, In vitro, Drug Combinations, chemistry, Immunology, HIV-1, Acriflavine, Zidovudine
Abstract: While none of the three drugs which exert an in vitro anti-HIV effect, neither AZT nor the other two. acriflavine and elliptinium, which we have shown to be more efficient than AZT, is able to eradicate Friend's virus in vivo , the combination of the 3 drugs at much smaller doses than when given alone seems able to eradicate it in almost 30% of the infected animals. This possible eradicatng effect of virostatics in combination is compared with the results we had previously obtained with lymphocytes of virus-immunized allogeneic donors. Friend's virus / virostatic chemotherapy / adoptive allogeneic Immunotherapy.
Published: 1990
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43. Design, synthesis and structure relationships of new N,N',N',N''-tetrakis (omega-amino alkyl) tetraazamacrocycles

Author: Trabaud C, Dessolin J, Camplo M, Hantz O, Fabien Zoulim, Borel C, Meyer M, Pepe G, Jc, Chermann, and Jl, Kraus
Subjects: Aza Compounds, Magnetic Resonance Spectroscopy, Spectrometry, Mass, Fast Atom Bombardment, Virus Replication, Antiviral Agents, Cell Line, Hepatitis B Virus, Duck, Structure-Activity Relationship, Ducks, Drug Design, DNA, Viral, HIV-1, Animals, Humans, Cells, Cultured
Abstract: A number of N,N',N",N"'-tetrakis (omega-aminoalkyl) tetraazamacrocycles and related compounds were synthesized and evaluated for their inhibitory effects on human immunodeficiency virus type 1 (HIV-1) and duck hepatitis B virus (DHBV) replication. The activity of these compounds was found to be highly dependent upon structural features: (i) the length of the alkyl linker connecting the nitrogen atoms of the macrocyclic ring to the exocyclic nitrogen atoms of the terminal amino groups (five methylenes favoured antiviral activity); (ii) substitution of the terminal amino groups of the linker reduced antiviral activity; and (iii) the size of the tetraazamacrocyclic ring (14 or 15 atoms) did not markedly affect the antiviral activity. Some analogues were potent inhibitors of HIV-1 replication, with anti-HIV activity similar to that of biscyclam (JM 2763). In contrast, other analogues were found to be highly toxic in duck hepatocyte primary culture, the 2.2.15 cell line and to a lesser extent in MT-4 cells. Structural parameters, macrocyclic ring size and metal-chelating ability have been used to develop a structure-activity relationship model in order to aid the design of antiviral molecules derived from N,N',N",N"'-tetrakis (omega-aminoalkyl) tetraazamacrocycles.
Published: 1999

44. Development of a reverse transcriptase PCR-enzyme-linked immunosorbent assay for quantification of human immunodeficiency virus type 1 RNA in plasma: comparison with commercial quantitative assays

Author: G Audoly, C. Trepo, M. Sepetjan, Mary-Anne Trabaud, K Leriche, Laurent Cotte, and J Ritter
Subjects: Microbiology (medical), RNA, virus diseases, Viremia, Quantitative Reverse Transcriptase PCR, Enzyme-Linked Immunosorbent Assay, HIV Infections, Biology, medicine.disease, Virology, Molecular biology, Polymerase Chain Reaction, Sensitivity and Specificity, Virus, law.invention, Reverse transcription polymerase chain reaction, Standard curve, law, medicine, HIV-1, Humans, Quantitative analysis (chemistry), Polymerase chain reaction, DNA Primers, Research Article
Abstract: A quantitative reverse transcriptase PCR assay with automated detection by nonradioactive hybridization was developed for the determination of human immunodeficiency virus (HIV) type 1 RNA levels. This assay is based on the use of an external standard curve with an internal standard. The accuracy of quantification was verified by comparison with reference commercial tests, the Chiron branched-DNA and Roche AMPLICOR HIV MONITOR assays. This assay was able to quantify viremia in patients with CD4 cell numbers below and above 500/mm3 and to quantify some HIV strains which could not be titrated by the MONITOR assay.
Published: 1997

45. Predictive value of HIV-1 RNA detection in plasma by branched DNA assay during long-term zidovudine therapy

Author: C. Trepo, P. Rougier, F. Chapuis, Mary-Anne Trabaud, F. Bailly, and L. Cotte
Subjects: Microbiology (medical), Adult, Male, medicine.medical_specialty, Randomization, Anti-HIV Agents, Placebo, Gastroenterology, Asymptomatic, Virus, Zidovudine, Double-Blind Method, Internal medicine, Blood plasma, medicine, Humans, Acquired Immunodeficiency Syndrome, business.industry, virus diseases, RNA, General Medicine, Branched DNA assay, Virology, Infectious Diseases, HIV-1, RNA, Viral, medicine.symptom, business, medicine.drug
Abstract: The predictive value of human immunodeficiency virus type 1 (HIV-1) RNA detection in plasma using branched DNA assay was studied in a subgroup of 36 asymptomatic HIV-1-infected patients enrolled in a multicenter, double-blind, randomized study. Patients were randomized to receive either zidovudine (AZT) 1 g/day or placebo and were monitored for a mean time of 61 months. HIV-1 RNA was detected in plasma using branched DNA assay at months 0, 6, 12, 24, and 36. HIV-1 RNA was detected at levels ofor = 10(4) RNA eq/ml (eq/ml) in 8.3% of the patients at baseline, and this percentage increased during the first two years in the placebo group only. The detection rate of HIV-1 RNA at three years was 50% in both the AZT and the placebo groups. HIV-1 RNA levels ranged from 10(4) to 478 x 10(3) RNA eq/ml. HIV-1 RNA was detected at levels ofor = 10(4) eq/ml a mean time of 19 +/- 13 months before progression to AIDS in 76.5% of progressing patients. In a multivariate analysis including baseline CD4+ count, the initial randomization group, HIV-1 RNA detection in plasma, and detection of p24 antigenemia during the first three years of follow-up, the best independent predictors of progression to AIDS at five years and the best independent predictors of death at five years were HIV-1 RNA detection in plasma and p24 antigenemia.
Published: 1996

46. Toxicity and activity of purified trichosanthin

Author: Claude Desgranges, Pierre Smets, Eliane Mandine, Paul Ferrari, Mary-Anne Trabaud, Rene Zalisz, and M. Rommain
Subjects: Trichosanthin, Microgram, T-Lymphocytes, Immunology, Pharmacognosy, Virus Replication, Antiviral Agents, Giant Cells, Cell Line, Immunology and Allergy, Humans, Amino Acids, Cytotoxicity, Chromatography, High Pressure Liquid, Syncytium, biology, virus diseases, biology.organism_classification, Virology, Molecular biology, Infectious Diseases, Cell culture, Toxicity, Chromatography, Gel, HIV-1, Electrophoresis, Polyacrylamide Gel, Trichosanthes kirilowii, Drugs, Chinese Herbal, Thymidine
Abstract: Trichosanthin was purified from fresh Chinese root tubers of Trichosanthes kirilowii and evaluated for anti-HIV activity. Trichosanthin inhibited syncytium formation between infected H9 cells and uninfected Sup-T1 cells from 0.5 to 4 micrograms/ml. Trichosanthin also inhibited HIV replication in H9 and CEM-SS cells at 1 microgram/ml, but was toxic for MT-4 cells (HTLV-I-positive), at doses greater than 0.25 microgram/ml. This new purification procedure confirms the anti-HIV activity of trichosanthin on some cell lines in different biological assays.
Published: 1991

47. Complement mediates human immunodeficiency virus type 1 infection of a human T cell line in a CD4- and antibody-independent fashion

Author: M D Kazatchkine, M A Trabaud, V. Boyer, C. Desgranges, and E Fischer
Subjects: T cell, viruses, T-Lymphocytes, Immunology, HIV Antibodies, Virus, Monocytes, Cell Line, medicine, Immunology and Allergy, Humans, Antibody-dependent enhancement, Opsonin, Acquired Immunodeficiency Syndrome, biology, Complement System Proteins, Articles, Virology, Complement system, Receptors, Complement, Antibody opsonization, Antigens, Differentiation, B-Lymphocyte, medicine.anatomical_structure, CD4 Antigens, biology.protein, Alternative complement pathway, HIV-1, Receptors, Complement 3d, Antibody
Abstract: Incubation of the human T cell lymphotropic virus (HTLV)-IIIB and HTLV-RF strains of human immunodeficiency virus type 1 (HIV-1) with normal seronegative human serum under conditions that allow complement activation resulted in enhancement of infection of the MT2 human T cell line cultured in the presence of low amounts of virus. Infection of MT2 cells was assessed by measuring reverse transcriptase activity in supernatants at day 9 of culture. Complement activation by viral suspensions occurred through the alternative pathway. Opsonization of HTLV-RF viral particles with complement was sufficient to allow a productive infection to occur in cells exposed to suboptimal amounts of virus. Infection of MT2 cells with suboptimal amounts of serum-opsonized HIV-1 was suppressed by blocking the C3dg receptor (CR2, CD21) on MT2 cells with monoclonal anti-CR2 antibody and rabbit F(ab')2 anti-mouse immunoglobulin antibodies. Blocking of the gp120-binding site on CD4 under similar experimental conditions had no inhibitory effect on infection of MT2 cells with opsonized virus. Opsonization of HIV-1 with seronegative serum also resulted in a CR2-mediated enhancement of the infection of normal peripheral blood mononuclear cells and T lymphocytes. These results indicate that complement in the absence of antibody may enhance infection of C3 receptor-bearing T cells with HIV-1, and that the interaction of opsonized virus with the CR2 receptor may result by itself in the infection of target T cells in a CD4- and antibody-independent fashion.
Published: 1991

48. Variants With Different Mutation Patterns Persist in the Quasispecies of Enfuvirtide-Resistant HIV-1 Population During and After Treatment In Vivo.

Author: Trabaud, Mary Anne, Cotte, Laurent, Labernardière, Jean Louis, Lebel-Binay, Sophie, Icard, Vinca, Tardy, Jean-Claude, Trepo, Christian, and Andre, Patrice
Subjects: *DRUG resistance, *DRUG efficacy, *HIV infections, *HIV, *THERAPEUTICS
Abstract: The article evaluates the genotypic and phenotypic resistance in 11 HIV-1-infected patients receiving enfuvirtide, as part of a salvage regimen. It shows that individual variability of the mutation pattern and persistence of strains without mutation in the region mainly targeted by enfuvirtide resistance probably reflect that fact that resistance to enfuvirtide may rely on regions of gp41 or gp120 other than residues 36 to 45.
Published: 2007
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49. Investigations into the cross-reactivity of rabbit antibodies raised against nonhomologous pairs of synthetic peptides derived from HIV-1 gp120 proteins.

Author: Krsmanovic, V., Biquard, J.-M., Sikorska-Walker, M., Cosic, I., Desgranges, C., Trabaud, M.-A., Whitfield, J.F., Durkin, J.P, Achour, A., and Hearn, M.T.W.
Abstract: The immunological cross-reactivity of several peptides with specific pattern-property characteristics related to the epitopes of human immunodeficiency virus type 1 (HIV-1) gp160/ 120 envelope proteins has been investigated. Proteins with similar primary structures can be expected to show functional or topographic similarities, such as specific epitopes which may cross-react with antibodies derived from the immunisation of animals with other members of the same protein family. These structure-function characteristics may be revealed as periodicities derived from presentations based on the discrete Fourier transformation of the distributions of various physico-chemical amino acid descriptors, constituting the polypeptide backbone and amino acid side-chains of the protein molecule. Such approaches, for example, have permitted prediction of periodicities corresponding to secondary structural motifs, including amphipathic α-helices and β-sheets, within protein sequences, and have helped to clarify potential binding sites for ligands, substrates or cofactors with interacting macromolecules. Based on this approach, characteristic periodicities have been identified which represent common Fourier transform spectral properties of the envelope (ENV) gpl60/120 glycoproteins from a range of HIV-1 isolates. In addition, similar periodicities have been detected as components of the discrete Fourier transform representation of the corresponding amino acid descriptors of the CD4 binding domain of gpl20. Accordingly, we have synthesised several peptides having periodic characteristics in their discrete Fourier transform representations similar to these HIV-1 proteins. These nonhomologous synthetic peptides induced cross-reactive antibodies in New Zealand White rabbits. Polyclonal antibodies raised to one of these peptides reacted with HIV-1 ENV gpl20-related proteins, as determined by enzyme-linked immunosorbent assay and Western blotting techniques. These findings provide further evidence for a role of immunological cross-reactivity and molecular biomimicry in the development of peptide-based vaccines directed against viral or bacterial pathogens. [ABSTRACT FROM AUTHOR]
Published: 1998
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50. Emerging mutations and associated factors in patients displaying treatment failure on an etravirine-containing regimen

Author: Jacqueline Cottalorda, Magali Bouvier-Alias, Cécile Henquell, Mary-Anne Trabaud, Anne-Geneviève Marcelin, Bernard Masquelier, Catherine Tamalet, Jacques Izopet, Laurence Morand-Joubert, Sophie Vallet, Annick Ruffault, Anne Signori-Schmuck, Philippe Flandre, Dominique Bettinger, Constance Delaugerre, Sylvie Rogez, Diane Descamps, and Vincent Calvez
Subjects: Cyclopropanes, Male, Oncology, medicine.medical_specialty, Anti-HIV Agents, Etravirine, HIV Infections, Drug resistance, Treatment failure, 03 medical and health sciences, Text mining, Pharmacotherapy, Internal medicine, Drug Resistance, Viral, Nitriles, medicine, Humans, Pharmacology (medical), Nevirapine, Treatment Failure, Pharmacology, 0303 health sciences, 030306 microbiology, business.industry, 030302 biochemistry & molecular biology, virus diseases, Viral Load, HIV Reverse Transcriptase, Reverse transcriptase, Benzoxazines, 3. Good health, Molecular Typing, Pyridazines, Regimen, Pyrimidines, Infectious Diseases, Alkynes, Mutation, Mutation (genetic algorithm), HIV-1, RNA, Viral, Reverse Transcriptase Inhibitors, Drug Therapy, Combination, Female, business, medicine.drug
Abstract: Background The aim of this study was to characterize the mutations selected upon failure on etravirine (ETR)-containing regimen in non-nucleoside reverse transcriptase inhibitors (NNRTIs)-experienced HIV-infected patients and the associated factors. Methods Forty-two patients displaying virological failure after a 6 months ETR-containing regimen were studied. For each patient the reverse transcriptase (RT) sequence at failure was compared with all the RT sequences available before introduction of ETR. The effect of baseline and failure HIV-1 RNA, HIV-1 subtype, baseline number of NNRTI resistance mutations, protease inhibitor and nucleoside RT inhibitor genotypic sensitivity scores, number of new drugs used in the treatment, and previous use of efavirenz or nevirapine on the selection of NNRTI resistance mutations were investigated. Results At failure, 12/42 (29%) patients showed development of at least 1 new NNRTI mutation (7 patients selected 1 mutation and 5 patients 2 mutations). NNRTI mutations selected were V179I (5 patients), V179L (1), V179F (2), L100I (1), K103N (2), Y181C (3), K101E (1), K101R (1) and H221Y (1). Univariate analysis showed that HIV-1 RNA level at failure ( P=0.033) and past exposure to efavirenz ( PConclusion In this study, 29% of viruses from patients experiencing ETR failure selected new NNRTI resistance mutations (at position V179 in 2/3 of cases) in a context of multiple NNRTI resistance mutations.

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