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1. 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

2. 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, Antimicrobial Resistance, Genetics, HIV/AIDS, Clinical Research, Infectious Diseases, Aetiology, 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

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. Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286/MOBIDIP): a multicentre, randomised, parallel, open-label, superiority trial

Author

Reynes, J, Delaporte, E, Koulla-Shiro, S, Ndour, CT, Sawadogo, AB, Seidy, M, Le Moing, V, Calmy, A, Ciaffi, L, Gueye, NF Ngom, Girard, PM, Eholie, S, Guiard-Schmid, JB, Chaix, ML, Kouanfack, C, Tita, I, Bazin, B, Garcia, P, Izard, S, Eymard-Duvernay, S, Peeters, M, Serrano, L, Cournil, A, Mbouyap, PR, Toby, R, Manga, N, Ayangma, L, Mpoudi, M, Zoungrana, Ngole J, Diallo, M, Aghokeng, AF, Guichet, E, Bell, O, Abessolo, H Abessolo, Djoubgang, MR, Manirakiza, G, Lamarre, G, Mbarga, T, Epanda, S, Bikie, A, Nke, T, Massaha, N, Nke, E, Bikobo, D, Olinga, J, Elat, O, Diop, A, Diouf, B, Bara, N, Fall, MB Koita, Kane, C Toure, Seck, FB, Ba, S, Njantou, P, Ndyaye, A, Fao, P, Traore, R, Sanou, Y, Bado, G, Coulibaly, M, Some, E, Some, J, Kambou, A, Tapsoba, A, Sombie, D, Sanou, S, Traore, B, Flandre, P, Michon, C, Drabo, J, Simon, F, Ciaffi, Laura, Koulla-Shiro, Sinata, Sawadogo, Adrien Bruno, Ndour, Cheik Tidiane, Eymard-Duvernay, Sabrina, Mbouyap, Pretty Rosereine, Ayangma, Liliane, Zoungrana, Jacques, Gueye, Ndeye Fatou Ngom, Diallo, Mohamadou, Izard, Suzanne, Bado, Guillaume, Kane, Coumba Toure, Aghokeng, Avelin Fobang, Peeters, Martine, Girard, Pierre Marie, Le Moing, Vincent, Reynes, Jacques, and Delaporte, Eric

Published
2017
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6. Impact de la phase d'instauration orale et de l'IMC sur la concentration de cabotegravir chez les patients initiant un traitement par cabotegravir et rilpivirine de longue durée d'action

Author

Rubenstein, E., primary, Diemer, M., additional, Goldwirt, L., additional, Lascoux-Combe, C., additional, Lafaurie, M., additional, Sellier, P., additional, Deville, L., additional, Chaix, ML., additional, Delaugerre, C., additional, and Molina, JM., additional

Published
2023
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7. Effect of incident hepatitis C infection on CD4(+) cell count and HIV RNA trajectories based on a multinational HIV seroconversion cohort

Author

van Santen, DK, van der Helm, JJ, Touloumi, G, Pantazis, N, Muga, R, Gunsenheimer-Bartmeyer, B, Gill, MJ, Sanders, E, Kelleher, A, Zangerle, R, Porter, K, Prins, M, Geskus, RB, Del Amo, J, Meyer, L, Bucher, HC, Chene, G, Hamouda, O, Pillay, D, Rosinska, M, Sabin, C, Olson, A, Cartier, A, Fradette, L, Walker, S, Babiker, A, De Luca, A, Fisher, M, Kelleher, T, Cooper, D, Grey, P, Finlayson, R, Bloch, M, Ramacciotti, T, Gelgor, L, Smith, D, Lutsar, I, Dabis, F, Thiebaut, R, Costagliola, D, Guiguet, M, Vanhems, P, Chaix, ML, Ghosn, J, Boufassa, F, Meixenberger, K, Bannert, N, Antoniadou, A, Chrysos, G, Daikos, GL, Katsarou, O, Rezza, G, Dorrucci, M, Monforte, AD, Schuitemaker, H, Sannes, M, Kran, AMB, Tor, J, de Olalla, PG, Cayla, J, Moreno, S, Monge, S, del Romero, J, Perez-Hoyos, S, Sonnerborg, A, Gunthard, H, Scherrer, A, Malyuta, R, Murphy, G, Johnson, A, Phillips, A, Morrison, C, Salata, R, Mugerwa, R, Chipato, T, Price, MA, Gilmour, J, Kamali, A, Karita, E, Burns, F, Giaquinto, C, Grarup, J, Kirk, O, Bailey, H, Anne, AV, Panteleev, A, Thorne, C, Aboulker, JP, Albert, J, Asandi, S, De Wit, S, Reiss, P, Gatell, J, Karpov, I, Ledergerber, B, Lundgren, J, Moller, C, Rakhmanova, A, Rockstroh, J, Sandhu, M, Dedes, N, Fenton, K, Pizzuti, D, Vitoria, M, Faggion, S, Frost, R, Raben, D, Schwimmer, C, and Scott, M

Subjects
hepatitis C virus, HIV RNA, CD4(+) cell count, HIV, MSM
Abstract

Background: Most studies on hepatitis C virus (HCV)/HIV-coinfection do not account for the order and duration of these two infections. We aimed to assess the effect of incident HCVinfection, and its timing relative to HIVseroconversion (HIVsc) in HIV-positiveMSM on their subsequent CD4(+) T-cell count and HIV RNA viral load trajectories. Methods: WeincludedMSMwithwell estimated dates ofHIVsc from 17 cohortswithin the CASCADE Collaboration. HCV-coinfected MSM were matched to as many HIV monoinfected MSM as possible by HIV-infection duration and combination antiretroviral therapy (cART) use. We used multilevel random-effects models stratified by cART use to assess differences inCD4(+) cell count andHIVRNAviral loadtrajectoriesbyHCV-coinfection status. Findings: Wematched 214 (ART-naive) and 147 (on cART) HCV-coinfectedMSMto 5384 and 3954, respectively, matched controls. The timing of HCV seroconversion (HCVsc) relative to HIVsc had no demonstrable effect on HIV RNA viral load or CD4(+) cell count trajectories. In the first 2-3 years following HCVsc CD4(+) cell counts were lower among HCV-coinfected MSM, but became comparable with HIV monoinfected MSM thereafter. In ART-naive MSM, during the first 2 years after HCVsc, HIV RNA viral load levels were lower or comparable with HIV monoinfected, tending to be higher thereafter. In MSM on cART, HCV had no significant effect on having a detectable HIV RNA viral load. Interpretation: Irrespective of the duration of HIV infection when HCV is acquired, CD4(+) cell counts were temporarily lower following HCVsc, even when on cART. The clinical implications of our findings remain to be further elucidated. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

Published
2019

9. Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286/MOBIDIP): a multicentre, randomised, parallel, open-label, superiority trial

Author

Ciaffi, Laura, primary, Koulla-Shiro, Sinata, additional, Sawadogo, Adrien Bruno, additional, Ndour, Cheik Tidiane, additional, Eymard-Duvernay, Sabrina, additional, Mbouyap, Pretty Rosereine, additional, Ayangma, Liliane, additional, Zoungrana, Jacques, additional, Gueye, Ndeye Fatou Ngom, additional, Diallo, Mohamadou, additional, Izard, Suzanne, additional, Bado, Guillaume, additional, Kane, Coumba Toure, additional, Aghokeng, Avelin Fobang, additional, Peeters, Martine, additional, Girard, Pierre Marie, additional, Le Moing, Vincent, additional, Reynes, Jacques, additional, Delaporte, Eric, additional, Reynes, J, additional, Delaporte, E, additional, Koulla-Shiro, S, additional, Ndour, CT, additional, Sawadogo, AB, additional, Seidy, M, additional, Le Moing, V, additional, Calmy, A, additional, Ciaffi, L, additional, Gueye, NF Ngom, additional, Girard, PM, additional, Eholie, S, additional, Guiard-Schmid, JB, additional, Chaix, ML, additional, Kouanfack, C, additional, Tita, I, additional, Bazin, B, additional, Garcia, P, additional, Izard, S, additional, Eymard-Duvernay, S, additional, Peeters, M, additional, Serrano, L, additional, Cournil, A, additional, Mbouyap, PR, additional, Toby, R, additional, Manga, N, additional, Ayangma, L, additional, Mpoudi, M, additional, Zoungrana, Ngole J, additional, Diallo, M, additional, Aghokeng, AF, additional, Guichet, E, additional, Bell, O, additional, Abessolo, H Abessolo, additional, Djoubgang, MR, additional, Manirakiza, G, additional, Lamarre, G, additional, Mbarga, T, additional, Epanda, S, additional, Bikie, A, additional, Nke, T, additional, Massaha, N, additional, Nke, E, additional, Bikobo, D, additional, Olinga, J, additional, Elat, O, additional, Diop, A, additional, Diouf, B, additional, Bara, N, additional, Fall, MB Koita, additional, Kane, C Toure, additional, Seck, FB, additional, Ba, S, additional, Njantou, P, additional, Ndyaye, A, additional, Fao, P, additional, Traore, R, additional, Sanou, Y, additional, Bado, G, additional, Coulibaly, M, additional, Some, E, additional, Some, J, additional, Kambou, A, additional, Tapsoba, A, additional, Sombie, D, additional, Sanou, S, additional, Traore, B, additional, Flandre, P, additional, Michon, C, additional, Drabo, J, additional, and Simon, F, additional

Published
2017
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10. A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

Author

TEMPRANO ANRS 12136 Study Group, Danel, C, Moh, R, Gabillard, D, Badje, A, Le Carrou, J, Ouassa, T, Ouattara, E, Anzian, A, Ntakpé, JB, Minga, A, Kouame, GM, Bouhoussou, F, Emieme, A, Kouamé, A, Inwoley, A, Toni, TD, Ahiboh, H, Kabran, M, Rabe, C, Sidibé, B, Nzunetu, G, Konan, R, Gnokoro, J, Gouesse, P, Messou, E, Dohoun, L, Kamagate, S, Yao, A, Amon, S, Kouame, AB, Koua, A, Kouamé, E, Ndri, Y, Ba-Gomis, O, Daligou, M, Ackoundzé, S, Hawerlander, D, Ani, A, Dembélé, F, Koné, F, Guéhi, C, Kanga, C, Koule, S, Séri, J, Oyebi, M, Mbakop, N, Makaila, O, Babatunde, C, Babatounde, N, Bleoué, G, Tchoutedjem, M, Kouadio, AC, Sena, G, Yededji, SY, Assi, R, Bakayoko, A, Mahassadi, A, Attia, A, Oussou, A, Mobio, M, Bamba, D, Koman, M, Horo, A, Deschamps, N, Chenal, H, Sassan-Morokro, M, Konate, S, Aka, K, Aoussi, E, Journot, V, Nchot, C, Karcher, S, Chaix, ML, Rouzioux, C, Sow, PS, Perronne, C, Girard, PM, Menan, H, Bissagnene, E, Kadio, A, Ettiegne-Traore, V, Moh-Semdé, C, Kouame, A, Massumbuko, JM, Chêne, G, Dosso, M, Domoua, SK, N'Dri-Yoman, T, Salamon, R, Eholié, SP, and Anglaret, X

Subjects
Adult, Male, medicine.medical_specialty, TEMPRANO ANRS 12136 Study Group, Antitubercular Agents, HIV Infections, law.invention, Time-to-Treatment, Randomized controlled trial, Acquired immunodeficiency syndrome (AIDS), law, Internal medicine, General & Internal Medicine, medicine, Clinical endpoint, Isoniazid, Humans, Tuberculosis, Adverse effect, Bacterial disease, AIDS-Related Opportunistic Infections, business.industry, Hazard ratio, General Medicine, 11 Medical And Health Sciences, Middle Aged, Viral Load, medicine.disease, Confidence interval, CD4 Lymphocyte Count, Cote d'Ivoire, Anti-Retroviral Agents, Asymptomatic Diseases, HIV-1, RNA, Viral, Female, business, Viral load, Follow-Up Studies
Abstract

Background In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. Methods We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. Results A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. Conclusions In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.).

Published
2015

11. Intensive five-drug antiretroviral therapy regimen versus standard triple-drug therapy during primary HIV-1 infection (OPTIPRIM-ANRS 147): a randomised, open-label, phase 3 trial

Author

Chéret, A, Nembot, G, Mélard, A, Lascoux, C, Slama, L, Miailhes, P, Yeni, P, Abel, S, Avettand-Fenoel, V, Venet, A, Chaix, Ml, Molina, Jm, Katlama, C, Goujard, C, Tamalet, C, Raffi, F, Lafeuillade, A, Reynes, J, Ravaux, I, Hoën, B, Delfraissy, Jf, Meyer, L, Rouzioux, C, Group, Optiprim Anrs Study, Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), Médecine interne [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier de Tourcoing, Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et tropicales [CHU Tenon], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de maladies infectieuses et tropicales, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Maladies Infectieuses et Tropicales [Fort-de-France, Martinique], CHU Fort de France-CHU de la Martinique [Fort de France]-Hôpital Pierre Zobda-Quitman [CHU de la Martinique], CHU de la Martinique [Fort de France], Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant, Laboratoire de virologie, 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), Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], 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), Service de santé publique et d'épidémiologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Virology, Hôpital de la Timone [CHU - APHM] (TIMONE), Maladies infectieuses et tropicales, Department of Infectious Diseases, General Hospital, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service des Maladies Infectieuses et Tropicales [Hôpital de la Conception] (SMIT), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), CHU Pointe-à-Pitre/Abymes [Guadeloupe], France REcherche Nord & sud Sida-hiv Hépatites (FRENSH), Inserm–ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck, and ViiV Laboratories, Asier Saez-Cirion collabore dans le groupe OPTIPRIM ANRS Study Group, Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) ( EA 7327 ), Université Paris Descartes - Paris 5 ( UPD5 ), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service des maladies infectieuses et tropicales, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Centre de Recherche en Cancérologie de Lyon ( 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 ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), CHU Fort de France-CHU de la Martinique-Hôpital Pierre Zobda-Quitman [CHU de la Martinique], CHU de la Martinique, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], 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, Hôpital de la Timone [CHU - APHM] ( TIMONE ), Recherches Translationnelles sur le VIH et les maladies infectieuses ( TransVIHMI ), Université de Montpellier ( UM ) -Universtié Yaoundé 1 [Cameroun]-Université Cheikh Anta Diop ( UCAD ) -Université Montpellier 1 ( UM1 ) -Institut de Recherche pour le Développement ( IRD ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service des Maladies Infectieuses et Tropicales [Hôpital de la Conception] ( SMIT ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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)-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), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), and Diallo, Ousseynatou

Subjects
Cart, Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, Mononuclear, Antiretroviral Therapy, HIV Infections, Emtricitabine, 03 medical and health sciences, chemistry.chemical_compound, immune system diseases, Internal medicine, Antiretroviral Therapy, Highly Active, medicine, Leukocytes, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Humans, Highly Active, education, Darunavir, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Maraviroc, 0303 health sciences, education.field_of_study, 030306 microbiology, business.industry, virus diseases, Middle Aged, Viral Load, Raltegravir, 3. Good health, Surgery, [SDV] Life Sciences [q-bio], Regimen, Infectious Diseases, Treatment Outcome, chemistry, Anti-Retroviral Agents, HIV-1, Leukocytes, Mononuclear, [SDV.IMM]Life Sciences [q-bio]/Immunology, Ritonavir, Female, France, business, medicine.drug
Abstract

International audience; BACKGROUND: Early combination antiretroviral therapy (cART) initiation at the time of primary HIV-1 infection could restrict the establishment of HIV reservoirs. We aimed to assess the effect of a cART regimen intensified with raltegravir and maraviroc, compared with standard triple-drug cART, on HIV-DNA load. METHODS: In this randomised, open-label, phase 3 trial, we recruited patients from hospitals across France. Inclusion criteria were primary HIV-1 infection (an incomplete HIV-1 western blot and detectable plasma HIV-RNA), with either symptoms or a CD4+ cell count below 500 cells per μL. Patients were randomly assigned (1:1) to an intensive, five-drug cART regimen (raltegravir 400 mg and maraviroc 150 mg twice daily, and a fixed-dose combination of tenofovir disoproxil fumarate 300 g plus emtricitabine 200 g, darunavir 800 g, and ritonavir 100 g once daily) or a standard triple-drug cART regimen (tenofovir disoproxil fumarate 300 g plus emtricitabine 200 g, darunavir 800 g, and ritonavir 100 g once daily) using a predefined randomised list generated by randomly selected variable block sizes. The primary endpoint was the median number of HIV-DNA copies per 10(6) peripheral blood mononuclear cells (PBMC) at month 24, analysed in the modified intention-to-treat population, defined as all patients who started their assigned treatment. This study is registered with ClinicalTrials.gov, number NCT01033760. FINDINGS: Between April 26, 2010, and July 13, 2011, 110 patients were enrolled, of whom 92 were randomly assigned and 90 started treatment (45 in each treatment group). Six (13%) patients in the intensive cART group and two (4%) in the standard cART group discontinued before month 24. At month 24, HIV-DNA loads were similar between groups (2·35 [IQR 2·05-2·50] log₁₀ per 10(6) PBMC in the intensive cART group vs 2·25 [1·71-2·55] in the standard cART group; p=0·21). Eight grade 3-4 clinical adverse events were reported in seven patients in the intensive cART group and seven grade 3-4 clinical adverse events were reported in seven patients in the standard cART group. Three serious clinical adverse events occurred: two (pancreatitis and lipodystrophy) in the standard cART group, which were regarded as treatment related, and one event (suicide attempt) in the intensive cART group that was unrelated to treatment. INTERPRETATION: After 24 months, cART intensified with raltegravir and maraviroc did not have a greater effect on HIV blood reservoirs than did standard cART. These results should help to design future trials of treatments aiming to decrease the HIV reservoir in patients with primary HIV-1 infection. FUNDING: Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck, and ViiV Laboratories.

Published
2015

12. The impact of transient combination antiretroviral treatment in early HIV infection on viral suppression and immunologic response in later treatment

Author

Pantazis, N, Touloumi, G, Meyer, L, Olson, A, Costagliola, D, Kelleher, AD, Lutsar, I, Chaix, ML, Fisher, M, Moreno, S, Porter, K, Pantazis, N, Touloumi, G, Meyer, L, Olson, A, Costagliola, D, Kelleher, AD, Lutsar, I, Chaix, ML, Fisher, M, Moreno, S, and Porter, K

Abstract

Objective: Effects of transient combination antiretroviral treatment (cART) initiated during early HIV infection (EHI) remain unclear. We investigate whether this intervention affects viral suppression and CD4+cell count increase following its reinitiation in chronic infection (CHI). Design: Longitudinal observational study. Methods: We identified adult patients from Concerted Action of Seroconversion to AIDS and Death in Europe who seroconverted after 1/1/2000, had a 12 months or less HIV test interval and initiated cART from naive. We classified individuals as 'pretreated in EHI' if treated within 6 months of seroconversion, interrupted for at least 12 weeks, and reinitiated during CHI. Statistical analysis was performed using survival analysis methods and mixed models. Results: Pretreated and initiated in CHI groups comprised 202 and 4263 individuals, with median follow-up after CHI treatment 4.5 and 3 years, respectively. Both groups had similar virologic response and relapse rates (P=0.585 and P=0.206) but pretreated individuals restarted treatment with higher baseline CD4+cell count (∼80cells/μl; P<0.001) and retained significantly higher CD4+cell count for more than 3 years after treatment (re)initiation. Assuming common baseline CD4+cell count, differences in CD4+cell count slopes were nonsignificant. Immunovirologic response to CHI treatment was not associated with timing or duration of the transient treatment. Conclusion: Although treatment interruptions are not recommended, stopping cART initiated in EHI does not seem to reduce the chance of a successful outcome of treatment in CHI.

Published
2016

13. An evaluation of HIV elite controller definitions within a large seroconverter cohort collaboration

Author

Olson, Ad, Meyer, L, Prins, M, Thiebaut, R, Gurdasani, D, Guiguet, M, Chaix, Ml, Amornkul, P, Babiker, A, Sandhu, Ms, Porter, K, Giaquinto, Carlo, CASCADE Collaboration in EuroCoord, University College of London [London] ( UCL ), 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 ), Public Health Service of Amsterdam, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), The Wellcome Trust Sanger Institute [Cambridge], University of Cambridge [UK] ( CAM ), 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 ), Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant, Université Paris Descartes - Paris 5 ( UPD5 ), International AIDS Vaccine Initiative [San Francisco] ( AVI ), HAL UPMC, Gestionnaire, University College of London [London] (UCL), 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), Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Cambridge [UK] (CAM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), International AIDS Vaccine Initiative [San Francisco] (AVI), 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), Medical Research Council Clinical Trials Unit ( MRC CTU ), Statistics In System biology and Translational Medicine ( SISTM ), Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH [Paris], Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], University of Texas Health Science Center, University of Texas at Houston [Houston] ( UTHealth ), Universitat de Barcelona, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Infectious diseases, Epidemiology and Data Science, Other departments, Experimental Immunology, and Global Health

Subjects
Time Factors, Epidemiology, Human immunodeficiency virus (HIV), lcsh:Medicine, HIV Infections, Communicable diseases, medicine.disease_cause, Men who have sex with men, Cohort Studies, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Antiretroviral Therapy, Highly Active, HIV Seropositivity, Medicine, 030212 general & internal medicine, Cooperative Behavior, lcsh:Science, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Public health, Multidisciplinary, Statistics, Hazard ratio, Antiretrovirals, HIV diagnosis and management, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, 3. Good health, AIDS, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HIV epidemiology, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious diseases, RNA, Viral, HIV clinical manifestations, Research Article, Cohort study, medicine.medical_specialty, Clinical Research Design, Sida, Sexually Transmitted Diseases, Viral diseases, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Internal medicine, VIH (Virus), Humans, Retrospective Studies, Demography, Proportional Hazards Models, 030304 developmental biology, [ SDV ] Life Sciences [q-bio], business.industry, Proportional hazards model, HIV (Viruses), lcsh:R, HIV, Malalties infeccioses, medicine.disease, Clinical disease, Salut pública, Antiretroviral agents, CD4 Lymphocyte Count, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Immunology, AIDS (Disease), lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Mathematics, Follow-Up Studies
Abstract

for C A S C A D E Collaboration in EuroCoord; International audience; Background: Understanding the mechanisms underlying viral control is highly relevant to vaccine studies and elite control (EC) of HIV infection. Although numerous definitions of EC exist, it is not clear which, if any, best identify this rare phenotype.Methods: We assessed a number of EC definitions used in the literature using CASCADE data of 25,692 HIV seroconverters. We estimated proportions maintaining EC of total ART-naïve follow-up time, and disease progression, comparing to non-EC. We also examined HIV-RNA and CD4 values and CD4 slope during EC and beyond (while ART naïve).Results: Most definitions classify ∼1% as ECs with median HIV-RNA 43–903 copies/ml and median CD4>500 cells/mm3. Beyond EC status, median HIV-RNA levels remained low, although often detectable, and CD4 values high but with strong evidence of decline for all definitions. Median % ART-naïve time as EC was ≥92% although overlap between definitions was low. EC definitions with consecutive HIV-RNA measurements 90% of measurements

Published
2014

14. The immunological and virological consequences of planned treatment interruptions in children with HIV infection

Author

Klein, Nigel, Sefe, Delali, Mosconi, Ilaria, Zanchetta, Marisa, Castro, Hannah, Jacobsen, Marianne, Jones, Hannah, Bernardi, Stefania, Pillay, Deenan, Giaquinto, Carlo, Walker, A. Sarah, Gibb, Diana M., De Rossi, Anita, Paediatric, European Network for Treatment of AIDS 11 Trial Team including Aboulker JP, Ananworanich, J, Babiker, A, Belfrage, E, Bernardi, S, Blanche, S, Bohlin, Ab, Bologna, R, Burger, Dm, Butler, K, Castelli Gattinara, G, Castro, H, Clayden, P, Compagnucci, A, Darbyshire, Jh, Debré, M, Faye, A, de Groot, R, della Negra, M, Duiculescu, D, Giaquinto, C, Gibb, Dm, Grosch Wörner, I, Hainault, M, Harper, L, Klein, N, Lallemant, M, Levy, J, Lyall, H, Marczynska, M, Mardarescu, M, Mellado Peña, Mj, Nadal, D, Niehues, T, Peckham, C, Pillay, D, Ramos Amador, Jt, Rosado, L, Rosso, R, Rudin, C, Saidi, Y, Scherpbier, Hj, Sharland, M, Stevanovic, M, Thorne, C, Tovo, Pier Angelo, Tudor Williams, G, Valerius, N, Walker, As, Welch, S, Wintergerst, U, Aboulker, Jp, Mofenson, L, Moye, J, Saïdi, Y, Cressey, Tr, Jacqz Aigrain, E, Khoo, S, Tréluyer, Jm, De Rossi, A, Ngo Giang Huong, N, Muñoz Fernandez, Ma, Hill, C, Lepage, P, Pozniak, A, Vella, S, Hadjou, G, Léonardo, S, Riault, Y, Buck, L, Farrelly, L, Forcat, S, Harrison, L, Horton, J, Johnson, D, Moore, S, Taylor, C, Chalermpantmetagul, S, Peongjakta, R, Chailert, S, Fregonese, F, Jourdain, G, Butler, D, Carlton, C, Collins, D, Kao, G, Van Buskirk, S, Watson, S, Corradini, S, Floret, D, Le Thi, Tt, Monpoux, F, Cottalorda, J, Lefebvre, Jc, Mellul, S, Boudjoudi, N, Firtion, G, Denon, M, Picard, F, Beniken, D, Damond, F, Alexandre, G, Tricoire, J, Nicot, F, Krivine, A, Rivaux, D, Chaix, Ml, Notheis, G, Strotmann, G, Schlieben, S, Rampon, O, Zanchetta, M, Ginocchio, F, Viscoli, C, Martino, A, Pontrelli, G, Concato, C, Mazza, A, Rossetti, G, Dobosz, S, Oldakowska, A, Popielska, J, Kaflik, M, Stanczak, J, Stanczack, G, Dyda, T, González Tomé, Mi, Delgado García, R, Fernandez Gonzalez, Mt, Martín Fontelos, P, Piñeiro Pérez, R, Penin, M, Garcia Mellado, I, Medina, Af, Ascencion, B, Garcia Bermejo, I, Garcia Vela, Ja, Martin Rubio, I, Gurbindo, D, Navarro Gomez, Ml, Jimenez, Jl, Garcia Torre, A, José Gómez, Mi, García Rodriguez, Mc, Moreno Pérez, D, Núñez Cuadros, E, Asensi Botet, F, Pérez, A, Pérez Tamarit, Md, Gobernado Serrano, M, Gonzales Molina, A, Kalhert, C, Dobrovoljac, M, Berger, C, Nobile, G, Reinhard, S, Schupbach, J, Bunupuradah, T, Puthanakit, T, Pancharoen, C, Butterworth, O, Phasomsap, C, Jupimai, T, Ubolyam, S, Phanuphak, P, Mai, C, Kanjanavanit, S, Namwong, T, Chutima, D, Raksasang, M, Foster, C, Hamadache, D, Campbell, S, Newbould, C, Monrose, C, Patel, D, Kaye, S, Seery, P, Wildfire, A, Novelli, V, Shingadia, D, Moshal, K, Flynn, J, Clapson, M, Allen, A, Spencer, L, Depala, M, Jacobsen, M, Mcmaster, P, Phipps, M, Orendi, J, Farmer, C, Liebeschuetz, S, Sodeinde, O, Wong, S, Heath, Y, Scott, S, Gandhi, K, Lewis, P, Daglish, J, Weiner, L, Famiglietti, M, Rana, S, Yu, P, Roa, J, Puga, A, Haerry, A, and Inma, A.

Subjects
CD31, Genetics and Molecular Biology (all), CD4-Positive T-Lymphocytes, Time Factors, T-CELL RECONSTITUTION, ACTIVE ANTIRETROVIRAL THERAPY, STRUCTURED TREATMENT INTERRUPTION, T-CELL RECONSTITUTION, HIV-1-INFECTED CHILDREN, IMMUNE RECONSTITUTION, THYMIC OUTPUT, 1-INFECTED CHILDREN, Adolescent, Anti-Retroviral Agents, CD8-Positive T-Lymphocytes, Child, Child, Preschool, Drug Administration Schedule, HIV Infections, Humans, Immunophenotyping, Lymphocyte Count, Treatment Outcome, Viral Load, Agricultural and Biological Sciences (all), Biochemistry, Genetics and Molecular Biology (all), Medicine (all), Biochemistry, law.invention, IMMUNE RECONSTITUTION, 0302 clinical medicine, Randomized controlled trial, law, 030212 general & internal medicine, HIV-1-INFECTED CHILDREN, 0303 health sciences, Multidisciplinary, ACTIVE ANTIRETROVIRAL THERAPY, 3. Good health, Medicine, Off Treatment, Poverty-related infectious diseases Infectious diseases and international health [N4i 3], THYMIC OUTPUT, Viral load, Research Article, Science, 1-INFECTED CHILDREN, Auto-immunity, transplantation and immunotherapy [N4i 4], 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), medicine, Preschool, 030304 developmental biology, business.industry, medicine.disease, Clinical trial, Immunology, STRUCTURED TREATMENT INTERRUPTION, business, CD8
Abstract

Contains fulltext : 126098.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To evaluate the immunological and viral consequences of planned treatment interruptions (PTI) in children with HIV. DESIGN: This was an immunological and virological sub-study of the Paediatric European Network for Treatment of AIDS (PENTA) 11 trial, which compared CD4-guided PTI of antiretroviral therapy (ART) with continuous therapy (CT) in children. METHODS: HIV-1 RNA and lymphocyte subsets, including CD4 and CD8 cells, were quantified on fresh samples collected during the study; CD45RA, CD45RO and CD31 subpopulations were evaluated in some centres. For 36 (18 PTI, 18 CT) children, immunophenotyping was performed and cell-associated HIV-1 DNA analysed on stored samples to 48 weeks. RESULTS: In the PTI group, CD4 cell count fell rapidly in the first 12 weeks off ART, with decreases in both naive and memory cells. However, the proportion of CD4 cells expressing CD45RA and CD45RO remained constant in both groups. The increase in CD8 cells in the first 12 weeks off ART in the PTI group was predominantly due to increases in RO-expressing cells. PTI was associated with a rapid and sustained increase in CD4 cells expressing Ki67 and HLA-DR, and increased levels of HIV-1 DNA. CONCLUSIONS: PTI in children is associated with rapid changes in CD4 and CD8 cells, likely due to increased cell turnover and immune activation. However, children off treatment may be able to maintain stable levels of naive CD4 cells, at least in proportion to the memory cell pool, which may in part explain the observed excellent CD4 cell recovery with re-introduction of ART.

Published
2013

15. Time to virological failure, treatment change and interruption for individuals treated within 12 months of HIV seroconversion and in chronic infection

Author

Zugna, D, Geskus, RB, De Stavola, B, Rosinska, M, Bartmeyer, B, Boufassa, F, Chaix, ML, Babiker, A, Porter, K, García de Olalla P., and CASCADE Collaboration EuroCoord

Abstract

Background: Estimates of treatment failure, change and interruption are lacking for individuals treated in early HIV infection. Methods: Using CASCADE data, we compared the effect of treatment in early infection (within 12 months of seroconversion) with that seen in chronic infection on risk of virological failure, change and interruption. Failure was defined as two subsequent measures of HIV RNA> 1,000 copies/ml following suppression (< 500 copies/ml), or > 500 copies/ml 6 months following initiation. Treatment change and interruption were defined as modification or interruption lasting > 1 week. In multivariable competing risks proportional subdistribution hazards models, we adjusted for combination antiretroviral therapy (cART) class, sex, risk group, age, CD4(+) T-cell count, HIV RNA and calendar period at treatment initiation. Results: Of 1,627 individuals initiating cART early (median 1.8 months from seroconversion), 159, 395 and 692 failed, changed and interrupted therapy, respectively. For 2,710 individuals initiating cART in chronic infection (median 35.9 months from seroconversion), the corresponding values were 266, 569 and 597. Adjusted hazard ratios (HRs; 95% CIs) for treatment failure and change were similar between the two treatment groups (0.93 [0.72, 1.20] and 1.06 [0.91, 1.24], respectively). There was an increasing trend in rates of interruption over calendar time for those treated early, and a decreasing trend for those starting treatment in chronic infection. Consequently, compared with chronic infection, treatment interruption was similar for early starters in the early cART period, but the relative hazard increased over calendar time (1.54 [1.33, 1.79] in 2000). Conclusions: Individuals initiating treatment in early HIV infection are more likely to interrupt treatment than those initiating later. However, rates of failure and treatment change were similar between the two groups.

Published
2012

16. Tracing the HIV-1 subtype B mobility in Europe: a phylogeographic approach

Author

Paraskevis, D, Pybus, O, Magiorkinis, G, Hatzakis, A, Wensing, Am, Van De Vijver, David, Albert, Jan, Angarano, Gioacchino, Asjo, B, Balotta, Claudia, Boeri, E, Camacho, Ricardo, Chaix, Ml, Coughlan, S, Costagliola, D, De Luca, Andrea, De Mendoza, C, Derdelinckx, I, Grossmann, Z, Hamouda, O, Hoepelman, I, Horban, A, Korn, K, Kucherer, C, Leitner, T, and Spread, Programme

Subjects
epidemiology, phylogenesis, HIV-1 subtype B, Settore MED/17 - MALATTIE INFETTIVE
Published
2009

17. Plasma drug concentrations and virologic evaluations after stopping treatment with nonnucleoside reverse-transcriptase inhibitors in HIV type 1-infected children

Author

Cressey, Tr, Green, H, Khoo, S, Treluyer, Jm, Compagnucci, A, Saidi, Y, Lallemant, M, Gibb, Dm, Burger, Dm, Collaborators: Aboulker JP, Paediatric European Network for Treatment of AIDS II Study G. r. o. u. p., Babiker, A, Blanche, S, Bohlin, Ab, Butler, K, Castelli Gattinara, G, Clayden, P, Darbyshire, Jh, Debré, M, de Groot, R, della Negra, M, Duicelescu, D, Giaquinto, C, Grosch Wörner, I, Kind, C, Levy, J, Lyall, H, Marczynska, M, Mellado Peña MJ, Nadal, D, Niehues, T, Peckham, C, Ramos Amador JT, Rosado, L, Rudin, C, Scherpbier, Hj, Sharland, M, Stevanovic, M, Tovo, Pier Angelo, Tudor Williams, G, Valerius, N, Walker, As, Wintergerst, U, Aboulker, Jp, Harper, L, Klein, N, Mofenson, L, Moye, J, Saïdi, Y, Jacqz Aigrain, E, Tréluyer, Jm, Clerici, M, De Rossi, A, Ngo Giang Huong, N, Muñoz Fernandez MA, Pillay, D, Hill, C, Lepage, P, Pozniak, A, Vella, S, Eliette, V, Hadjou, G, Léonardo, S, Pitrou, C, Riault, Y, Buck, L, Farrelly, L, Johnson, D, Taylor, C, Chalermpantmetagul, S, Peongjakta, R, Chailert, S, Fregonese, F, Jourdain, G, Butler, D, Carlton, C, Collins, D, Kao, G, Van Buskirk, S, Watson, S, Corradini, S, Floret, D, Laplace, J, Monpoux, F, Cottalorda, J, Lefebvre, Jc, Mellul, S, Boudjoudi, N, Firtion, G, Faye, A, Beniken, D, Damond, F, Tricoire, J, Krivine, A, Chaix, Ml, Notheis, G, Strotmann, G, Schlieben, S, Rampon, O, Zanchetta, M, Rosso, R, Repeto, E, Vitale, F, Martino, A, Bernardi, S, Mazza, A, Rossetti, G, Dobosz, S, Oldakowska, A, Popielska, J, Kaflik, M, Stanczak, J, Stanczac, T, González Tomé MI, Delgado García, R, José Mellado Peña, M, Martín Fontelos, P, Piñeiro Pérez, R, Alimenti, A, Penin, M, Gurbindo, D, Navarro Gomez ML, Jimenez, Jl, Prieto, C, de José Gómez MI, García Rodriguez MC, Moreno Pérez, D, Núñéz Cuadros, E, Asensi Botet, F, Pérez, A, Pérez Tamarit MD, Kalhert, C, Schupbach, J, Bunupuradah, T, Ananworanich, J, Phanuphak, P, Intasan, J, Ubolyam, S, Kanjanavanit, S, Namwong, T, Foster, C, Hamadache, D, Campbell, S, Hanley, C, Walsh, C, Kaye, S, Seery, P, Novelli, V, Shingadia, D, Flynn, J, Clapson, M, Jacobsen, M, Mcmaster, P, Hawkes, E, Liebeschuetz, S, Sodeinde, O, Wong, S, Walsh, S, Heath, Y, Weiner, L, Famiglietti, M, Rana, S, Yu, P, Roa, J, Puga, A, Haerry, A, Regazzi, M, Villani, S, Gibbons, S, Jullien, V, Rey, E, Treluye, Jm, Rodríguez Nóvoa, S, Tawon, Y., University of Zurich, and Green, H

Subjects
Cyclopropanes, Male, Time Factors, Infectious diseases and international health [NCEBP 13], HIV Infections, Drug resistance, Pharmacology, THERAPY, PROPHYLAXIS, 2726 Microbiology (medical), chemistry.chemical_compound, Plasma, immune system diseases, Medicine, Child, Reverse-transcriptase inhibitor, RESISTANCE, THERAPY, EXPOSURE, PHARMACOGENETICS, PROPHYLAXIS, virus diseases, Drug holiday, Viral Load, Infectious Diseases, Alkynes, Child, Preschool, Reverse Transcriptase Inhibitors, Female, Viral load, medicine.drug, Microbiology (medical), medicine.medical_specialty, Efavirenz, Nevirapine, Adolescent, CD4-CD8 Ratio, 610 Medicine & health, Article, Invasive mycoses and compromised host [N4i 2], Internal medicine, Drug Resistance, Viral, Humans, Protease inhibitor (pharmacology), EXPOSURE, PHARMACOGENETICS, business.industry, Poverty-related infectious diseases [N4i 3], 2725 Infectious Diseases, Benzoxazines, CD4 Lymphocyte Count, Regimen, chemistry, Withholding Treatment, 10036 Medical Clinic, Mutation, HIV-1, Microbial pathogenesis and host defense [UMCN 4.1], business, RESISTANCE
Abstract

Contains fulltext : 71467.pdf (Publisher’s version ) (Open Access) BACKGROUND: The optimum strategy for stopping treatment with drugs that have different half-lives in a combination regimen to minimize the risk of selecting drug-resistant viruses remains unknown. We evaluated drug concentrations in plasma, human immunodeficiency virus (HIV) load, and development of drug resistance after a planned treatment interruption of a nonnucleoside reverse-transcriptase inhibitor (NNRTI)-containing regimen in HIV type 1-infected children. METHODS: Children with viral loads or =30% (for children aged 2-6 years) or CD4 cell percentages > or =25% and CD4 cell counts > or =500 cells/microL (for children aged 7-15 years) were randomized to either a planned treatment interruption or to continuous therapy. In the planned treatment interruption arm, either (1) treatment with nevirapine or efavirenz was stopped, and treatment with the remaining drugs was continued for 7-14 days, or (2) nevirapine or efavirenz were replaced by a protease inhibitor, and all drugs were stopped after 7-14 days. Sampling for determination of plasma drug concentrations, measurement of viral load, and drug resistance testing was scheduled at day 0, day 7 (drug concentrations only), day 14, and day 28 after interruption of treatment with an NNRTI. RESULTS: Treatment with an NNRTI was interrupted for 35 children (20 were receiving nevirapine, and 15 were receiving efavirenz). Median time from NNRTI cessation to stopping all drugs was 9 days (range, 6-15 days) for nevirapine and 14 days (range, 6-18 days) for efavirenz. At 7 days, 1 (5%) of 19 and 4 (50%) of 8 children had detectable nevirapine and efavirenz concentrations, respectively; efavirenz remained detectable in 3 (25%) of 12 children at 14 days. At 14 days, viral load was > or =50 copies/mL in 6 of 16 children interrupting treatment with nevirapine (range, 52-7000 copies/mL) and in 2 of 12 children interrupting treatment with efavirenz (range, 120-1600 copies/mL). No new NNRTI mutations were observed. CONCLUSIONS: In children with virological suppression who experienced interruption of treatment with an NNRTI, staggered or replacement stopping strategies for a median of 9 days for nevirapine and 14 days for efavirenz were not associated with the selection of NNRTI resistance mutations.

Published
2008

18. The calculated genetic barrier for antiretroviral drug resistance substitutions is largely similar for different HIV-1 subtypes

Author

van de Vijver, DA Wensing, AMJ Angarano, G Asjo, B and Balotta, C Boeri, E Camacho, R Chaix, ML Costagliola, D and De Luca, A Derdelinckx, I Grossman, Z Hamouda, O and Hatzakis, A Hemmer, R Hoepelman, A Horban, A Korn, K and Kucherer, C Leitner, T Loveday, C MacRae, E Maljkovic, I and de Mendoza, C Meyer, L Nielsen, C de Coul, ELMO and Ormaasen, V Paraskevis, D Perrin, L Puchhammer-Stockl, E and Ruiz, L Salminen, M Schmit, JC Schneider, F Schuurman, R and Soriano, V Stanczak, G Stanojevic, M Vandamme, AM and Van Laethem, K Violin, M Wilbe, K Yerly, S Zazzi, M and Boucher, CAB SPREAD Programme

Abstract

Background: The genetic barrier, defined as the number of mutations required to overcome drug-selective pressure, is an important factor for the development of HIV drug resistance. Because of high variability between subtypes, particular HIV-1 subtypes could have different genetic barriers for drug resistance substitutions. This study compared the genetic barrier between subtypes using some 2000 HIV-1 sequences (> 600 of non-B subtype) isolated from antiretroviral-naive patients in Europe. Methods: The genetic barrier was calculated as the sum of transitions (scored as 1) and/or transversions (2.5) required for evolution to any major drug resistance substitution. In addition, the number of minor protease substitutions was determined for every subtype. Results: Few dissimilarities were found. An increased genetic barrier was calculated for 182A (subtypes C and G), V 1081 (subtype G), V 1181 (subtype G), Q 15 1 M (subtypes D and F), L210W (subtypes C, F, G, and CRF02_AG), and P225H (subtype A) (P < 0.001 compared with subtype B). A decreased genetic barrier was found for I82T (subtypes C and G) and V106M (subtype C) (P < 0.001 vs subtype B). Conversely, minor protease substitutions differed extensively between subtypes. Conclusions: Based on the calculated genetic barrier, the rate of drug resistance development may be similar for different HIV-1 subtypes. Because of differences in minor protease substitutions, protease inhibitor resistance could be enhanced in particular subtypes once the relevant major substitutions are selected.

Published
2006

19. Prevalence of drug-resistant HIV-1 variants in untreated individuals in Europe: Implications for clinical management

Author

Wensing, AMJ van de Vijver, DA Angarano, G Asjo, B and Balotta, C Boeri, E Camacho, R Chaix, ML Costagliola, D and De Luca, A Derdelinckx, I Grossman, Z Hamouda, O and Hatzakis, A Hemmer, R Hoepelman, A Horban, A Korn, K and Kucherer, C Leitner, T Loveday, C MacRae, E Maljkovic, I and de Mendoza, C Meyer, L Nielsen, C de Coul, ELO and Ormaasen, V Paraskevis, D Perrin, L Puchhammer-Stockl, E and Ruiz, L Salminen, M Schmit, JC Schneider, F Schuurman, R and Soriano, V Stanczak, G Stanojevic, M Vandamme, AM and Van Laethem, K Violin, M Wilbe, K Yerly, S Zazzi, M and Boucher, CA SPREAD Programme

Abstract

Background. Infection with drug-resistant human immunodeficiency virus type 1 (HIV-1) can impair the response to combination therapy. Widespread transmission of drug-resistant variants has the disturbing potential of limiting future therapy options and affecting the efficacy of postexposure prophylaxis. Methods. We determined the baseline rate of drug resistance in 2208 therapy-naive patients recently and chronically infected with HIV-1 from 19 European countries during 1996-2002. Results. In Europe, 1 of 10 antiretroviral-naive patients carried viruses with >= 1 drug-resistance mutation. Recently infected patients harbored resistant variants more often than did chronically infected patients (13.5% vs. 8.7%; P = .006). Non-B viruses (30%) less frequently carried resistance mutations than did subtype B viruses (4.8% vs. 12.9%;). Baseline resistance increased over time in newly diagnosed cases of non-B infection: from P

Published
2005

20. Lopinavir/Ritonavir Monotherapy as a Nucleoside Analogue–Sparing Strategy to Prevent HIV-1 Mother-to-Child Transmission: The ANRS 135 PRIMEVA Phase 2/3 Randomized Trial

Author

Tubiana, Roland, primary, Mandelbrot, Laurent, additional, Le Chenadec, Jérome, additional, Delmas, Sandrine, additional, Rouzioux, Christine, additional, Hirt, Deborah, additional, Treluyer, Jean-Marc, additional, Ekoukou, Dieudonné, additional, Bui, Eda, additional, Chaix, Marie-Laure, additional, Blanche, Stéphane, additional, Warszawski, Josiane, additional, Ngondi, J, additional, Chernai, N, additional, Teglas, JP, additional, Laurent, C, additional, Huyn, P, additional, Le Chenadec, J, additional, Delmas, S, additional, Warszawski, J, additional, Muret, P, additional, Baazia, Y, additional, Jeantils, V, additional, Lachassine, E, additional, Rodrigues, A, additional, Sackho, A, additional, Sagnet-Pham, I, additional, Tassi, S, additional, Breilh, D, additional, Iriard, X, additional, Andre, G, additional, Douard, D, additional, Reigadas, S, additional, Roux, D, additional, Louis, I, additional, Morlat, P, additional, Pedebosq, S, additional, Barre, J, additional, Estrangin, E, additional, Fauveau, E, additional, Garrait, V, additional, Ledudal, P, additional, Pichon, C, additional, Richier, L, additional, Thebault, A, additional, Touboul, C, additional, Bornarel, D, additional, Chambrin, V, additional, Clech, L, additional, Dubreuil, P, additional, Foix L'helias, L, additional, Picone, O, additional, Schoen, H, additional, Stralka, M, additional, Crenn-Hebert, C, additional, Floch-Tudal, C, additional, Hery, E, additional, Ichou, H, additional, Mandelbrot, L, additional, Meier, F, additional, Tournier, V, additional, Walter, S, additional, Chevojon, P, additional, Devidas, A, additional, Granier, M, additional, Khanfar-boudjemai, M, additional, Malbrunot, C, additional, Nguyen, R, additional, Ollivier, B, additional, Radideau, E, additional, Turpault, I, additional, Jault, T, additional, Barrail, A, additional, Colmant, C, additional, Fourcade, C, additional, Goujard, C, additional, Pallier, C, additional, Peretti, D, additional, Taburet, AM, additional, Bocket, L, additional, D'angelo, S, additional, Godart, F, additional, Hammou, Y, additional, Houdret, N, additional, Mazingue, F, additional, Thielemans, B, additional, Brochier, C, additional, Cotte, L, additional, Januel, F, additional, Le Thi, T, additional, Gagneux, MC, additional, Bozio, A, additional, Massardier, J, additional, Kebaïli, K, additional, Ben, Akli K, additional, Heller-Roussin, B, additional, Riehl, C, additional, Roos, S, additional, Taccot, F, additional, Winter, C, additional, Arias, J, additional, Brunet-François, C, additional, Dailly, E, additional, Flet, L, additional, Gournay, V, additional, Mechinaud, F, additional, Reliquet, V, additional, Winner, N, additional, Peytavin, G, additional, Bardin, C, additional, Boudjoudi, N, additional, Compagnucci, A, additional, Guerin, C, additional, Krivine, A, additional, Pannier, E, additional, Salmon, D, additional, Treluyer, JM, additional, Firtion, G, additional, Ayral, D, additional, Ciraru-Vigneron, N, additional, Mazeron, MC, additional, Rizzo Badoin, N, additional, Trout, H, additional, Benachi, A, additional, Boissand, C, additional, Bonnet, D, additional, Boucly, S, additional, Blanche, S, additional, Chaix, ML, additional, Duvivier, C, additional, Parat, S, additional, Cayol, V, additional, Oucherif, S, additional, Rouzioux, C, additional, Viard, JP, additional, Bonmarchand, M, additional, De Montgolfier, I, additional, Dommergues, M, additional, Fievet, MH, additional, Iguertsira, M, additional, Pauchard, M, additional, Quetin, F, additional, Soulie, C, additional, Tubiana, R, additional, Faye, A, additional, Magnier, S, additional, Bui, E, additional, Carbonne, B, additional, Daguenel Nguyen, A, additional, Harchi, N, additional, Meyohas, MC, additional, Poirier, JM, additional, Rodriguez, J, additional, Hervé, F, additional, Pialloux, G, additional, Dehee, A, additional, Dollfus, C, additional, Tillous Borde, I, additional, Vaudre, G, additional, Wallet, A, additional, Allemon, MC, additional, Bolot, P, additional, Boussairi, A, additional, Chaplain, C, additional, Ekoukou, D, additional, Ghibaudo, N, additional, Kana, JM, additional, Khuong, MA, additional, Weil, M, additional, Entz-Werle, N, additional, Livolsi Lutz, P, additional, Beretz, L, additional, Cheneau, M, additional, Partisani, ML, additional, Schmitt, MP, additional, Acar, P, additional, Armand, E, additional, Berrebi, A, additional, Guibaud Plo, C, additional, Lavit, M, additional, Nicot, F, additional, Tricoire, J, additional, Ajana, F, additional, and Huleux, T, additional

Published
2013
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23. Low risk of nevirapine resistance mutations in the prevention of mother-to-child transmission of HIV-1: Agence Nationale de Recherches sur le SIDA Ditrame Plus, Abidjan, Cote d'Ivoire.

Author

Chaix ML, Ekouevi DK, Rouet F, Tonwe-Gold B, Viho I, Bequet L, Peytavin G, Toure H, Menan H, Leroy V, Dabis F, Rouzioux C, and Agence Nationale de Recherches sur le SIDA Ditrame Plus Study Group

Abstract

The frequency of resistance mutations was estimated in the cohort of Agence Nationale de Recherches sur le SIDA Ditrame Plus, a study that evaluated the combination of short-course zidovudine (ZDV) plus lamivudine (3TC) and single-dose nevirapine (SD-NVP) followed by 3 days of postpartum ZDV plus 3TC for the prevention of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1). The frequency with which resistance mutations were detected in mothers at week 4 postpartum was 1.14% (95% confidence interval [CI], 0.03%-6.17%) for NVP and 8.33% (95% CI, 3.66%-15.76%) for 3TC. In multivariate analysis, 3TC resistance was associated with a longer duration of ZDV plus 3TC prepartum prophylaxis (P=.009). This regimen, which is feasible in resource-limited settings, prevents most peripartum HIV-1 transmission and minimizes the development of NVP resistance. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Published
2006
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24. Differences in the frequency of minor substitutions between HIV-1 subtypes and their potential impact on the genetic barrier for resistance to protease inhibitors

Author

Vijver, Damc, Wensing, Amj, Angarano, G., Asjo, B., Balotta, C., Boeri, E., Camacho, R., Chaix, Ml, Costagliola, D., Coul, Elmo, Luca, A., Maljkovic, I., Mendoza, C., Derdelinckx, I., Grossman, Z., Hamouda, O., Hatzakis, A., Hoepelman, Im, Hemmer, R., Horban, A., Korn, K., Kucherer, C., Leitner, T., Loveday, C., Macrae, E., Meyer, L., Nielsen, C., Ormaasen, V., Perrin, L., Paraskevis, D., Puchhammer-Stockl, E., Ruiz, L., Salminen, M., Schmit, Jcc, Schneider, F., Schuurman, R., Vicente Soriano, Stanczak, G., Stanojevic, M., Vandamme, Am, Laethem, K., Violin, M., Wilbe, K., Yerly, S., Zazzi, M., and Boucher, Cab

25. Differences in the frequency of minor substitutions between HIV-1 subtypes and their potential impact on the genetic barrier for resistance to protease inhibitors

Author

Vijver, Dv, Wensing, Amj, Angarano, G., Asjo, B., Balotta, C., Boeri, E., Camacho, R., Chaix, Ml, Costagliola, D., Coul, Elmo, Luca, A., Maljkovic, I., Mendoza, C., Derdelinckx, I., Grossman, Z., Hamouda, O., Hatzakis, A., Hoepelman, Im, Hemmer, R., Horban, A., Korn, K., Kucherer, C., Leitner, T., Loveday, C., Macrae, E., Meyer, L., Nielsen, C., Ormaasen, V., Perrin, L., Paraskevis, D., Puchhammer-Stockl, E., Ruiz, L., Salminen, M., Schmit, Jcc, Schneider, F., Schuurman, R., Soriano, V., Stanczak, G., Stanojevic, M., Anne-Mieke Vandamme, Laethem, K., Violin, M., Wilbe, K., Yerly, S., Zazzi, M., Boucher, Cab, and Spread, Programme

26. Low-dose ritonavir-boosted darunavir in virologically suppressed HIV-1-infected adults: an open-label trial (ANRS 165 Darulight)

Author

Jean-Michel, Molina, Sebastien, Gallien, Marie-Laure, Chaix, El Mountacer, El Abbassi, Isabelle, Madelaine, Christine, Katlama, Nadia, Valin, Pierre, Delobel, Kristell, Desseaux, Gilles, Peytavin, Juliette, Saillard, François, Raffi, Sylvie, Chevret, S, Gibowski, 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), Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), Laboratoire de Virologie [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), Service de biostatistiques et information médicale [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service des 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), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], 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), Département de Pharmacologie [AP-HP Hôpital Bichat - Claude Bernard], AP-HP - Hôpital Bichat - Claude Bernard [Paris], ANRS France Recherche Nord & sud Sida-hiv hépatites, 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), Département des Maladies Infectieuses [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), ANRS 165 Darulight Study Group : Ponscarme D, Lascoux C, Girard PM, Rami A, Yazdanpanah Y, Simon A, Tubiana R, Duvivier C, Jeantils V, Loreillard D, Poizot-Martin I, Bernard L, Gras G, Allavena C, Bernaud C, Bouchez S, Hall N, Reliquet V, Raffi F, De Truchis P, Charreau I, Bocquet L, Lemoing V, Point G, Molina JM, Chevret S, El Abbassi EM, Gallien S, Tattevin P, Gras G, Chaix ML, Peytavin G, Saillard J, Couffin-Cadiergues S, Madelaine I, Diallo A, Gibowski S., 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)-CHU Necker - Enfants Malades [AP-HP], Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], and Dupuis, Christine

Subjects
Adult, Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, HIV Infections, Emtricitabine, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Abacavir, Internal medicine, Humans, Medicine, Pharmacology (medical), 030212 general & internal medicine, Darunavir, Pharmacology, Ritonavir, business.industry, virus diseases, Lamivudine, HIV Protease Inhibitors, Middle Aged, Viral Load, 030112 virology, 3. Good health, Discontinuation, Regimen, Treatment Outcome, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, RNA, Viral, Reverse Transcriptase Inhibitors, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Drug Therapy, Combination, Female, business, Viral load, medicine.drug
Abstract

International audience; Objectives:To assess whether low-dose ritonavir-boosted darunavir (darunavir/r) in combination with two NRTIs could maintain virological suppression in patients on a standard regimen of darunavir/r + two NRTIs.Design:A multicentre, Phase II, non-comparative, single-arm, open-label study.Setting:Tertiary care hospitals in France.Subjects:One hundred HIV-1-infected adults with no darunavir or NRTI resistance-associated mutations (RAMs) and a plasma HIV RNA level ≤50 copies/mL for ≥12 months on once-daily darunavir/r (800/100 mg) + two NRTIs for ≥6 months were switched to darunavir/r 400/100 mg with the same NRTIs.Primary outcome measure:Proportion of patients with treatment success: plasma HIV RNA level ≤50 copies/mL up to 48 weeks without any change in the study regimen, in a modified ITT (mITT) analysis.Results:At baseline, most patients were male (78%), with a median age of 43 years, median duration of HIV RNA ≤50 copies/mL of 35 months and median CD4 T cell count of 633 cells/mm3. Seventy-six percent received tenofovir/emtricitabine and 24% abacavir/lamivudine. Five patients were excluded from the mITT analysis. The rate of treatment success through to week 48 was 91.6% (87/95; 95% CI 84.1%-96.3%). No RAM was detected in three amplifiable genotypes. A total of 212 adverse events (AEs) occurred in 64 patients (64%); 9 AEs were serious, none leading to treatment discontinuation.Conclusions:In HIV-infected patients well suppressed with darunavir/r (800/100 mg) and two NRTIs, a reduction of the darunavir dose to 400 mg/day maintained virological efficacy and was safe over 48 weeks.

Published
2018

27. Universal test and treat and the HIV epidemic in rural South Africa: a phase 4, open-label, community cluster randomised trial

Author

Collins C Iwuji, Joanna Orne-Gliemann, Joseph Larmarange, Eric Balestre, Rodolphe Thiebaut, Frank Tanser, Nonhlanhla Okesola, Thembisa Makowa, Jaco Dreyer, Kobus Herbst, Nuala McGrath, Till Bärnighausen, Sylvie Boyer, Tulio De Oliveira, Claire Rekacewicz, Brigitte Bazin, Marie-Louise Newell, Deenan Pillay, François Dabis, Collins Iwuji, Kevi Naidu, Tulio de Oliveira, Tamsen Rochat, Johannes Viljoen, Thembelihle Zuma, Sophie Karcher, Melanie Plazy, Mélanie Prague, Rodolphe Thiébaut, Thierry Tiendrebeogo, Hermann Donfouet, Andrea Gosset, Laura March, Camelia Protopopescu, Bruno Spire, Alexandra Calmy, Maxime Inghels, Hassimiou Diallo, Vincent Calvez, Anne Derache, Anne-Geneviève Marcelin, Rosemary Dray-Spira, France Lert, Kamal El Farouki, Richard Lessells, Kenneth Freedberg, John Imrie, Marie-Laure Chaix, Colin Newell, Jan Hontelez, Africa Health Research Institute [Durban/Mtubatuba] (AHRI), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), University of Southampton, Brighton and Sussex Medical School (BSMS), Research Department of Infection and Population Health [London], University College of London [London] (UCL), Santé, vulnérabilités et relations de genre au sud (SAGESUD - ERL Inserm U1244), Centre population et développement (CEPED - UMR_D 196), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), School of nursing and public health [Durban, KwaZulu-Natal, South Africa], University of KwaZulu-Natal (UKZN), Academic Unit of Primary Care and Population Sciences [Southampton, UK] (Department of Social statistics & Demography), Department of Global Health and Population [Boston, MA, USA] (Harvard School of Public Health), Harvard University [Cambridge], Institute of Public Health [Heidelberg, Germany] (Medical School), Ruprecht-Karls-University [Heidelberg, Germany], Nelson R Mandela School of Medicine [Durban, KwaZulu-Natal, South Africa] (College of Health Sciences), Human Health and Development [Southampton, UK] (Global Health Research Institute), Division of Infection and Immunity [London, UK], Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS 12249 TasP Study Group : Bärnighausen T, Herbst K, Iwuji C, Makowa T, Naidu K, Newell ML, Okesola N, de Oliveira T, Pillay D, Rochat T, Tanser F, Viljoen J, Zuma T, McGrath N, Balestre E, Dabis F, Karcher S, Orne-Gliemann J, Plazy M, Prague M, Thiébaut R, Tiendrebeogo T, Boyer S, Donfouet H, Gosset A, March L, Protopopescu C, Spire B, Calmy A, Larmarange J, Inghels M, Diallo H, Calvez V, Derache A, Marcelin AG, Dray-Spira R, Lert F, El Farouki K, Lessells R, Freedberg K, Imrie J, Chaix ML, Newell C, Hontelez J, Bazin B, Rekacewicz C., Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre population et développement (CEPED - UMR_D 196), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité)-Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), School of nursing and public health, University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN), Harvard School of Public Health, Global Health Research Institute, Division of Immunity and Infection, The Medical School, Edgbaston, Dupuis, Christine, and Harvard University

Subjects
0301 basic medicine, Cyclopropanes, Male, Epidemiology, HIV Infections, TaSP, law.invention, chemistry.chemical_compound, South Africa, 0302 clinical medicine, Randomized controlled trial, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HIV Seropositivity, Emtricitabine, Mass Screening, 030212 general & internal medicine, education.field_of_study, Incidence (epidemiology), Incidence, Hazard ratio, Middle Aged, 3. Good health, SISTM, Infectious Diseases, Treatment Outcome, Research Design, Alkynes, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, medicine.drug, Adult, medicine.medical_specialty, Efavirenz, Adolescent, Anti-HIV Agents, Immunology, Population, IDLIC, 03 medical and health sciences, Young Adult, Virology, medicine, Humans, education, Tenofovir, Mass screening, business.industry, 030112 virology, Benzoxazines, chemistry, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Demography
Abstract

BackgroundUniversal antiretroviral therapy (ART), as per the 2015 WHO recommendations, might reduce population HIV incidence. We investigated the effect of universal test and treat on HIV acquisition at population level in a high prevalence rural region of South Africa.MethodsWe did a phase 4, open-label, cluster randomised trial of 22 communities in rural KwaZulu-Natal, South Africa. We included individuals residing in the communities who were aged 16 years or older. The clusters were composed of aggregated local areas (neighbourhoods) that had been identified in a previous study in the Hlabisa subdistrict. The study statisticians randomly assigned clusters (1:1) with MapInfo Pro (version 11.0) to either the control or intervention communities, stratified on the basis of antenatal HIV prevalence. We offered residents repeated rapid HIV testing during home-based visits every 6 months for about 4 years in four clusters, 3 years in six clusters, and 2 years in 12 clusters (58 cluster-years) and referred HIV-positive participants to trial clinics for ART (fixed-dose combination of tenofovir, emtricitabine, and efavirenz) regardless of CD4 cell count (intervention) or according to national guidelines (initially ≤350 cells per μL and FindingsBetween March 9, 2012, and June 30, 2016, we contacted 26 518 (93%) of 28 419 eligible individuals. Of 17 808 (67%) individuals with a first negative dried blood spot test, 14 223 (80%) had subsequent dried blood spot tests, of whom 503 seroconverted after follow-up of 22 891 person-years. Estimated HIV incidence was 2·11 per 100 person-years (95% CI 1·84–2·39) in the intervention group and 2·27 per 100 person-years (2·00–2·54) in the control group (adjusted hazard ratio 1·01, 95% CI 0·87–1·17; p=0·89). We documented one case of suicidal attempt in a woman following HIV seroconversion. 128 patients on ART had 189 life-threatening or grade 4 clinical events: 69 (4%) of 1652 in the control group and 59 (4%) of 1367 in the intervention group (p=0·83).InterpretationThe absence of a lowering of HIV incidence in universal test and treat clusters most likely resulted from poor linkage to care. Policy change to HIV universal test and treat without innovation to improve health access is unlikely to reduce HIV incidence.FundingANRS, GiZ, and 3ie.

Published
2018

28. Safety and immunogenicity of double-dose versus standard-dose hepatitis B revaccination in non-responding adults with HIV-1 (ANRS HB04 B-BOOST): a multicentre, open-label, randomised controlled trial

Author

Eric Billaud, Marie-Josée Wendling, Georges Haour, Fabrice Carrat, Philippe Sogni, Lionel Piroth, Patrick Miailhes, David Rey, Faiza Ajana, Alexandra Rohel, Jean-Michel Molina, Cécilie Dufour, Marie-Louise Michel, Odile Launay, Le Trait d'Union, centre de soins de l'infection par le VIH [CHU Strasbourg], CHU Strasbourg, Département d'infectiologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de Virologie [Strasbourg], Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Pathogenèse des Virus de l'Hépatite B (PVHB), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANRS France Recherche Nord & sud Sida-hiv hépatites, Service des Maladies Infectieuses et Tropicales [Hôpital Gustave Dron, Tourcoing], Centre Hospitalier Gustave Dron [Tourcoing], Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CIC Cochin Pasteur (CIC 1417), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe hospitalier Broca-Université Paris Descartes - Paris 5 (UPD5)-Hôtel-Dieu-Hôpital Cochin [AP-HP], Département de santé publique [AP-HP Groupe Hospitalier Est Parisien], Hôpitaux universitaires Est parisien [AP-HP], French National Institute for Medical Research (Inserm)., French National Agency for Research on AIDS and Viral Hepatitis (ANRS)., ANRS HB04 B-BOOST study group : Aumaitre H, Berger JL, Devidas A, Abgrall S, Patey O, Thiebaut MC, Lucht F, Hoen B, Lascoux-Combe C, Lortholary O, Delcey V, De Truchis P, Jeantils V, Vittecoq D, Slama L, Zucman D, Levy Y, Katlama C, Simon A, Girard PM, Molina JM, Pierre-Francois S, Chennebault JM, Le Berre R, Neau D, Livrozet JM, Poizot-Martin I, Matheron S, Reynes J, Billaud É, Perre P, Durand J, Rosenthal É, Arvieux C, Cuzin L, Verdon R, Leclercq P, Ajana F, May T, Debab Y, Lefort A, Delacroix I, Beck-Wirth G, Poinsignon Y, Prazuck T, Philibert P, Viard JP, Andrieu M, Rey D, Carrat F, Launay O, Piroth L, Miailhes P, Ajana F, Sogni P, Michel ML, Wendling MJ, Rohel A, Dufour C, Bailly F, Hanslik T, Touze E, Pol S, Aboulker JP, Chaix ML, Gougeon ML, Allain L, Kaabeche K, Simony M, Rohel A, Metro A, Diallo A, Mendy Y, Paul C, Carrat F, van der Vliet D, Martin K, Pouget N, Dorival C, Dufour C, Rabiéga P, Bendriss R, Lutton O, Duflos Y, N'Diaye A, Boinet S, Toubiwou E, Madouni A, Kutala C, Chevallot C, Goderel I, Pourteau V, Quimbert S, Pannetier G, Bitchiné S, Sallé AV, Chau F., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5)-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM), and Lissalde, Claire

Subjects
Male, Pediatrics, efficacy, HIV Infections, Booster dose, law.invention, 0302 clinical medicine, Randomized controlled trial, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, vaccine, Single-Blind Method, 030212 general & internal medicine, Vaccines, Synthetic, 0303 health sciences, number, infected patient, Middle Aged, Hepatitis B, 3. Good health, Vaccination, Treatment Outcome, Infectious Diseases, homosexual man, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, Viral hepatitis, Adult, medicine.medical_specialty, Hepatitis B vaccine, Immunization, Secondary, virus, Young Adult, 03 medical and health sciences, medicine, Humans, Hepatitis B Vaccines, Hepatitis B Antibodies, Aged, Intention-to-treat analysis, 030306 microbiology, business.industry, medicine.disease, rate, Regimen, injection, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, impaired response
Abstract

Equipe CHU UB (EA) Pôle MERS CT3 Hors Enjeu ANRS HB04 B-BOOST study group : Hugues Aumaitre (Centre Hospitalier Marechal Joff re, Perpignan, France); Jean-Luc Berger (Centre Hospitalier Universitaire de Reims– Hopital Robert Debre, Reims, France); Alain Devidas (Hopital Gilles de Corbeil–Centre Hospitalier Sud Francilien, Corbeil Essonne, France); Sophie Abgrall (Centre Hospitalier Universitaire Avicenne, Avicenne, France); Olivier Patey (Centre Hospitalier Intercommunal de Villeneuve St Georges, Villeneuve Saint Georges, France); Marie-Christine Drobacheff Thiebaut (Centre Hospitalier Universitaire de Besancon–Hopital Saint Jacques, Besancon, France); Frederic Lucht (Centre Hospitalier Universitaire de St Etienne–Hopital Nord, Saint Etienne, France); Bruno Hoen (Centre Hospitalier Universitaire de Besancon–Hopital Saint Jacques, Besancon, France); Caroline Lascoux-Combe (Hopital Saint Louis, Paris, France); Olivier Lortholary (Hopital Necker, Paris, France); Veronique Delcey (Hopital Lariboisiere, Paris, France); Pierre De Truchis (Hopital Raymond–Poincare, Garches, France); Vincent Jeantils (Hopital Jean Verdier, Bondy, France); Daniel Vittecoq (Le Kremlin Bicetre, France); Laurence Slama (Hopital Tenon, Paris, France); David Zucman (Hopital Foch, Suresnes, France); Yves Levy (Hopital Henri Mondor, Creteil, France); Christine Katlama (Hopital Pitie Salpetriere, Paris, France); Anne Simon (Hopital Pitie Salpetriere, Paris, France); Pierre-Marie Girard (Hopital Saint Antoine, Paris, France); Jean-Michel Molina (CISIH, Hopital Saint Louis, Paris, France); Sandrine Pierre-Francois (Centre Hospitalier Universitaire de Fort de France–Hopital Pierre Zobda Quitman, Fort de France, France); Jean-Marie Chennebault (Centre Hospitalier Universitaire d’Angers–Hopital de l’Hotel Dieu, Angers, France); Rozenn Le Berre (Centre Hospitalier Universitaire de Brest– Hopital de La Cavale Blanche, Brest, France); Didier Neau (Hopital Pellegrin, Bordeaux, France); Jean Michel Livrozet (Hopital Edouard Herriot, Lyon, France); Isabelle Poizot-Martin (Hopital Sainte Marguerite, Marseille, France); Sophie Matheron (Hopital Bichat, Paris, France); Jacques Reynes (Hopital Gui De Chauliac, Montpellier, France); Eric Billaud (Centre Hospitalier Universitaire de Nantes–Hotel Dieu, Nantes, France); Philippe Perre (Centre Hospitalier Departemental de Vendee–Les Oudairies, La Roche sur Yon, France); Jacques Durand (Centre Hospitalier Universitaire de Nice–Hopital de l’Archet, Nice, France); Eric Rosenthal (Centre Hospitalier Universitaire de Nice–Hopital de l’Archet, Nice, France); Cedric Arvieux (Centre Hospitalier Universitaire de Rennes–Hopital Pontchaillou, Rennes, France); Lize Cuzin (Centre Hospitalier Universitaire de Toulouse–Hopital Purpan, Toulouse, France); Renaud Verdon (Centre Hospitalier Universitaire Cote de Nacre, Caen, France); Pascale Leclercq (Centre Hospitalier Universitaire de Grenoble–Hopital Albert Michallon, Grenoble, France); Faiza Ajana (Hopital Gustave Dron, Tourcoing, France); Thierry May (Centre Hospitalier Universitaire Nancy–Hopital Brabois, Nancy, France); Yasmine Debab (Centre Hospitalier Universitaire de Rouen–Hopital Charles Nicolle, Rouen, France); Agnes Lefort (Hopital Beaujon, Clichy, France); Isabelle Delacroix (Centre Hospitalier Intercommunal de Creteil, Creteil, France); Genevieve Beck-Wirth (Hopital du Moenchberg, Mulhouse, France); Yves Poinsignon (Centre Hospitalier Bretagne-Atlantique Vannes, Vannes, France); Thierry Prazuck (Centre Hospitalier Regional–Hopital de La Source, Orleans, France); Patrick Philibert (Hopital Europeen Marseille, Marseille, France); Jean-Paul Viard (Hopital Hotel Dieu, Paris, France).; International audience; BACKGROUND:Revaccination with double-dose hepatitis B vaccine has been recommended in HIV-infected patients who do not respond to standard vaccination, but has not yet been assessed. We aimed to compare the safety and immunogenicity of a reinforced hepatitis B revaccination protocol with the standard revaccination schedule in HIV-infected patients not responding to primary vaccination.METHODS:We did this multicentre, open-label, randomised controlled trial, at 53 centres in France. HIV-infected adults (aged ≥18 years), with CD4 counts of 200 cells per μL or more and no response to a previous hepatitis B vaccination or a 20 μg booster dose, were randomly assigned (1:1), according to a computer-generated randomisation list with permuted blocks (block sizes of two to six), to receive either standard-dose (20 μg) or double-dose (40 μg) recombinant hepatitis B vaccine at weeks 0, 4, and 24. Randomisation was stratified by baseline CD4 count (200-349 vs ≥350 cells per μL). Patients and treating physicians were not masked to treatment allocation, but the randomisation list was concealed from the investigators who assigned participants to the vaccination groups. The primary endpoint was the proportion of responders, defined as patients with hepatitis B surface antibody (anti-HBs) titres of 10 mIU/mL or more, at week 28. We did analysis by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00670839.FINDINGS:Between May 19, 2008, and May 8, 2011, 178 participants were randomly assigned to the standard-dose group (n=90) or the double-dose group (n=88), of whom 176 (98%) participants were included in the primary efficacy analysis. At week 28, we recorded a response in 60 patients (67%, 95% CI 57-77) in the standard-dose group versus 64 patients (74%, 63-82) in the double-dose group (p=0·334). Except for more frequent local reactions in the double-dose group than the standard-dose group (13 [15%] vs four [4%] patients; p=0·020), there was no difference in safety between groups.INTERPRETATION:In adults with HIV-1 who have not responded to previous hepatitis B vaccination, double-dose revaccination did not achieve a higher response rate than did revaccination with standard single-dose regimen. However, the safety profile was similar between treatment groups. Our results should be assessed in future studies before double-dose vaccine can be considered for the standard of care of vaccine non-responders.FUNDING:French National Institute for Medical Research-French National Agency for Research on AIDS and Viral Hepatitis.

Published
2015

29. Susceptibility to lenacapavir, fostemsavir and broadly neutralizing antibodies in French primary HIV-1 infected patients in 2020-2023.

Author

Chaix ML, Terracol L, Nere ML, Stefic K, Lascoux-Combe C, Manda V, Sellier P, Maylin S, Molina JM, Liegeon G, Delaugerre C, and Salmona M

Subjects
Humans, France epidemiology, Male, Female, Adult, Middle Aged, Organophosphates pharmacology, Genotype, HIV Antibodies immunology, Piperazines, HIV Infections virology, HIV Infections drug therapy, HIV Infections epidemiology, HIV Infections immunology, HIV-1 drug effects, HIV-1 immunology, HIV-1 genetics, Antibodies, Neutralizing immunology, Anti-HIV Agents therapeutic use, Anti-HIV Agents pharmacology, Drug Resistance, Viral genetics
Abstract

Surveillance studies of Transmitted Drug Resistance (TDR) are crucial in tracking the evolution of HIV epidemiology. Our aim was to investigate TDR to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase inhibitors (INIs), as well as to new drugs: lenacapavir, fostemsavir. Predictive sensitivity was evaluated for maraviroc and broadly neutralizing antibodies (bNAbs) (zinlirvimab and teropavimab). Between 2020 and 2023, 85 people with HIV (PWH) were diagnosed with primary HIV-1 infection (PHI). Pol and env sequences were analyzed and TDR was characterized according to the French ANRS algorithm. The genotypic-based prediction of bNAbs sensitivity was based on HIV env amino acid signatures I108, I201, F353 for teropavimab and N325, N332, H330 for zinlirvimab. TDR to NRTIs, NNRTIs, PIs and INIs was evidenced in 8.2%, 12.9%, 4.7%, and 5.9% strains, respectively. Ten viruses were CXCR4/dual mix. All viruses were susceptible to lenacapavir (100%) and 52% harbored resistance to fostemsavir. The genotypic profile was associated with a predictive positive value (PPV) > 83% of susceptibility to both teropavimab and zinlirvimab for 23 viruses (31%), while 22 (29%) had a PPV between 62% and 75%, suggesting reduced susceptibility to both bNAbs as soon as primary infection. The surveillance of TDR evidenced at the time of PHI is important with regard to new strategies for HIV patients with virological failure and global implementation of PrEP using NRTI, INI such as recently approved injectable cabotegravir, and future long-acting drugs such as lenacapavir and bNAbs., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Published
2024
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30. Low cabotegravir trough concentrations without oral lead-in in patients with HIV-1 switching to long-acting cabotegravir and rilpivirine.

Author

Rubenstein E, Diemer M, Goldwirt L, Lascoux-Combe C, Chaix ML, Rami A, Ponscarme D, Lafaurie M, Denis B, De Castro N, Gras J, Liegeon G, Sellier PO, Deville L, Chevret S, Delaugerre C, and Molina JM

Subjects
Humans, Male, Female, Middle Aged, Adult, Drug Substitution, Administration, Oral, Plasma chemistry, Diketopiperazines, Pyridones administration & dosage, Rilpivirine administration & dosage, Rilpivirine therapeutic use, Rilpivirine pharmacokinetics, HIV Infections drug therapy, Anti-HIV Agents administration & dosage, Anti-HIV Agents pharmacokinetics, Anti-HIV Agents therapeutic use, HIV-1 isolation & purification
Abstract

In a cohort of 72 consecutive virologically-suppressed patients with HIV-1 switching to long-acting cabotegravir and rilpivirine, we observed low cabotegravir trough concentrations 1 and 3 months after the first injection, with a significant association with no oral lead-in at 1 month [odds ratio (OR) = 6.3 [95% confidence interval (CI) 1.7-29.5], P = 0.01] and three months (OR = 5.6 [95% CI 1.3-29.7], P = 0.03), and with high BMI at 1 month (OR = 1.3 [95% CI 1.1-1.6], P = 0.007)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2024
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31. Correction: COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants.

Author

Bay P, Audureau E, Préau S, Favory R, Guigon A, Heming N, Gault E, Pham T, Chaghouri A, Turpin M, Morand-Joubert L, Jochmans S, Pitsch A, Meireles S, Contou D, Henry A, Joseph A, Chaix ML, Uhel F, Roux D, Descamps D, Emery M, Garcia-Sanchez C, Levy D, Burrel S, Mayaux J, Kimmoun A, Hartard C, Pène F, Rozenberg F, Gaudry S, Brichler S, Guillon A, Handala L, Tamion F, Moisan A, Daix T, Hantz S, Delamaire F, Thibault V, Souweine B, Henquell C, Picard L, Botterel F, Rodriguez C, Dessap AM, Pawlotsky JM, Fourati S, and de Prost N

Published
2024
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32. Prevalence of pretreatment HIV resistance to integrase inhibitors in West African and Southeast Asian countries.

Author

Aghokeng AF, Ngo-Giang-Huong N, Huynh THK, Dagnra AY, D'Aquin Toni T, Maiga AI, Dramane K, Eymard-Duvernay S, Chaix ML, Calvez V, and Descamps D

Subjects
Humans, Africa, Western epidemiology, Asia, Southeastern epidemiology, Mutation, Prevalence, Drug Resistance, Viral genetics, HIV Infections drug therapy, HIV Infections virology, HIV Infections epidemiology, HIV Integrase genetics, HIV Integrase Inhibitors pharmacology, HIV Integrase Inhibitors therapeutic use, HIV-1 drug effects, HIV-1 genetics
Abstract

Objectives: Integrase strand transfer inhibitors (INSTIs) have been recently recommended as the preferred first-line option for antiretroviral treatment initiators in low- and middle-income countries (LMICs) in response to the growing circulation of resistant HIV to non-nucleoside reverse transcriptase inhibitors (NNRTIs). In this study, we estimated the frequency of pretreatment drug resistance (PDR) to INSTIs in West Africa and Southeast Asia., Materials and Methods: Using samples collected from 2015 to 2016, and previously used to assessed PI, NRTI and NNRTI resistance, we generated HIV integrase sequences and identified relevant INSTI PDR mutations using the Stanford and ANRS algorithms., Results: We generated 353 integrase sequences. INSTI PDR frequency was low, 1.1% (4/353) overall, ranging from 0% to 6.3% according to country. However, frequency of PDR to any drug class was very high, 17.9% (95% CI: 13.9%-22.3%), and mostly associated with a high level of NNRTI PDR, 9.7%, and a moderate level of NRTI PDR, 5.3%., Conclusions: Our results support the recent introduction of INSTIs in LMICs to improve treatment outcome in these settings, but also stress the need for effective actions to prevent uncontrolled emergence of drug resistance to this drug class., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2024
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33. COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants.

Author

Bay P, Audureau E, Préau S, Favory R, Guigon A, Heming N, Gault E, Pham T, Chaghouri A, Turpin M, Morand-Joubert L, Jochmans S, Pitsch A, Meireles S, Contou D, Henry A, Joseph A, Chaix ML, Uhel F, Roux D, Descamps D, Emery M, Garcia-Sanchez C, Levy D, Burrel S, Mayaux J, Kimmoun A, Hartard C, Pène F, Rozenberg F, Gaudry S, Brichler S, Guillon A, Handala L, Tamion F, Moisan A, Daix T, Hantz S, Delamaire F, Thibault V, Souweine B, Henquell C, Picard L, Botterel F, Rodriguez C, Dessap AM, Pawlotsky JM, Fourati S, and de Prost N

Abstract

Background: During the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11-28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants., Methods: This is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria., Results: 566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4-7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay., Conclusion: This study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients., (© 2024. The Author(s).)

Published
2024
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34. Failure of bamlanivimab with selection of E484K mutation in an allogeneic stem cell transplant recipient with nosocomial SARS-CoV-2 infection.

Author

Boussen I, Salmona M, Sicre De Fontbrune F, Xhaard A, De Castro N, Delaugerre C, Chaix ML, and Molina JM

Subjects
Humans, SARS-CoV-2, Antibodies, Neutralizing, Mutation, Stem Cell Transplantation, Cross Infection drug therapy, COVID-19 diagnosis, Hematopoietic Stem Cell Transplantation adverse effects, Antibodies, Monoclonal, Humanized
Abstract

We report the case of an allogeneic stem cell transplant recipient with nosocomial acquisition of SARS-CoV-2 infection who received antispike neutralizing monoclonal antibody bamlanivimab 2 days after diagnosis of SARS-CoV-2 infection but progressed to severe COVID-19 pneumonia and died with the selection of E484K/Q resistance mutations to bamlanivimab., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Published
2024
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35. Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron variants BA.2, BA.5 and BQ.1.1 in critically ill patients with COVID-19: a prospective, multicenter cohort study.

Author

de Prost N, Audureau E, Préau S, Favory R, Guigon A, Bay P, Heming N, Gault E, Pham T, Chaghouri A, Voiriot G, Morand-Joubert L, Jochmans S, Pitsch A, Meireles S, Contou D, Henry A, Joseph A, Chaix ML, Uhel F, Descamps D, Emery M, Garcia-Sanchez C, Luyt CE, Marot S, Pène F, Lhonneur AS, Gaudry S, Brichler S, Picard L, Mekontso Dessap A, Rodriguez C, Pawlotsky JM, and Fourati S

Abstract

Background: Despite current broad natural and vaccine-induced protection, a substantial number of patients infected with emerging SARS-CoV-2 variants (e.g., BF.7 and BQ.1.1) still experience severe COVID-19. Real-life studies investigating the impact of these variants on clinical outcomes of severe cases are currently not available. We performed a prospective multicenter observational cohort study. Adult patients with acute respiratory failure admitted between December 7, 2021 and December 15, 2022, in one of the 20 participating intensive care units (17 from the Greater Paris area and 3 from the North of France) were eligible for inclusion if they had SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR). Full-length SARS-CoV-2 genomes from all included patients were sequenced by means of next-generation sequencing. The primary endpoint of the study was day-28 mortality., Results: The study included 158 patients infected with three groups of Omicron sublineages, including (i) BA.2 variants and their early sublineages referred as "BA.2" (n = 50), (ii) early BA.4 and BA.5 sublineages (including BA.5.1 and BA.5.2, n = 61) referred as "BA.4/BA.5", and (iii) recent emerging BA.5 sublineages (including BQ.1, BQ.1.1, BF.7, BE.1 and CE.1, n = 47) referred as "BQ.1.1". The clinical phenotype of BQ1.1-infected patients compared to earlier BA.2 and BA.4/BA.5 sublineages, showed more frequent obesity and less frequent immunosuppression. There was no significant difference between Omicron sublineage groups regarding the severity of the disease at ICU admission, need for organ failure support during ICU stay, nor day 28 mortality (21.7%, n = 10/47 in BQ.1.1 group vs 26.7%, n = 16/61 in BA.4/BA.5 vs 22.0%, n = 11/50 in BA.2, p = 0.791). No significant relationship was found between any SARS-CoV-2 substitution and/or deletion on the one hand and survival on the other hand over hospital follow-up., Conclusions: Critically-ill patients with Omicron BQ.1.1 infection showed a different clinical phenotype than other patients infected with earlier Omicron sublineage but no day-28 mortality difference., (© 2023. The Author(s).)

Published
2023
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36. Transmission of S230R integrase drug resistance mutation affecting second-generation integrase inhibitors in a French primary HIV-1 infected man.

Author

Salmona M, Lascoux-Combe C, Nere ML, Rubenstein E, Molina JM, Delaugerre C, and Chaix ML

Subjects
Male, Humans, Integrase Inhibitors pharmacology, Integrase Inhibitors therapeutic use, Mutation, Integrases genetics, Drug Resistance, Viral genetics, Heterocyclic Compounds, 3-Ring therapeutic use, HIV-1 genetics, Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Integrase Inhibitors pharmacology, HIV Integrase Inhibitors therapeutic use, HIV Integrase genetics
Published
2023
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38. Hepatitis A and B vaccine uptake and immunisation among men who have sex with men seeking PrEP: a substudy of the ANRS IPERGAY trial.

Author

Le Turnier P, Charreau I, Gabassi A, Carette D, Cotte L, Pialoux G, Tremblay C, Spire B, Chaix ML, Meyer L, Capitant C, Delaugerre C, Raffi F, and Molina JM

Subjects
Adult, Humans, Male, Hepatitis A Antibodies, Hepatitis A Vaccines, Hepatitis B Antibodies, Hepatitis B Vaccines, Hepatitis B virus, Homosexuality, Male, Immunoglobulin G, Vaccination, Hepatitis A prevention & control, Hepatitis A virus, Sexual and Gender Minorities
Abstract

Vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended in men who have sex with men (MSM). We assessed HAV and HBV vaccine uptake in the non-immune participants and their immunisation during follow-up of the ANRS IPERGAY (Intervention Préventive de l'Exposition aux Risques avec et pour les Gays) pre-exposure prophylaxis (PrEP) trial.During the ANRS IPERGAY trial among MSM (NCT01473472), vaccination against HAV and HBV was offered free of charge to all non-immune participants at baseline. We assessed anti-HAV IgGs and anti-hepatitis B surface (HBs) antibodies (Abs) at baseline, 1-3 months after each vaccine dose and on the last follow-up visit. Vaccination uptake and immunisation were analysed in non-immune participants with at least 6 months of follow-up after the 1st vaccine dose.A total of 427 MSM with a median age of 34.8 years were analysed. Median follow-up was 2.2 years (Q1-Q3, 1.6-2.9). Absence of anti-HAV IgG at baseline (50.4%, 215/427) was associated with younger age (p=0.0001). Among HAV non-immune participants, 96.1% (197/205) received one or more vaccine doses and 91.0% (172/189) received two vaccine doses. Among HBV non-immune participants, 97.6 % (81/83) received one or more vaccine doses and 78.4% (58/74) received three doses. On the last-visit sample, anti-HAV IgG and anti-HBs Abs were respectively detected in 94.8% (95% CI 90.0% to 97.7%) and 79.6% (95% CI 66.5% to 89.4%) of participants with complete vaccination and in 80.0% (95% CI 51.9% to 95.7%) and 40.0% (95% CI 16.3% to 67.7%) of participants with incomplete vaccination.Vaccine acceptability against HAV and HBV infections was very high in MSM starting PrEP. Immunisation was high in participants with a full vaccination scheme. Physicians must consider PrEP visits as major opportunities to propose and complete HAV and HBV vaccination in at-risk non-immune subjects., Competing Interests: Competing interests: J-MM reports grants from Gilead and participated to advisory board for Gilead, Merck and ViiV for studies unrelated to this current work. GP reports grants from Gilead and Bristol Myers Squibb and personal fees (board membership) from Gilead, Bristol Myers Squibb, Boehrringer Ingelheim, Nephrotek, ViiV Healthcare, Abbvie and MSD for studies unrelated to this current work. FR reports personal fees from Gilead, Janssen, MSD, Theratechnologies and ViiV Healthcare for studies unrelated to this current work. All other authors report no potential conflicts and have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2023
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39. Prevalence and incidence of HEV among men using HIV pre-exposure prophylaxis: A sub-study of the ANRS IPERGAY trial.

Author

Chaix ML, Leturque N, Gabassi A, Charreau I, Minier M, Pialoux G, Cua É, Chidiac C, Raffi F, Tremblay C, Meyer L, Molina JM, and Delaugerre C

Subjects
Humans, Male, Homosexuality, Male, Incidence, Prevalence, Seroepidemiologic Studies, Hepatitis E epidemiology, Hepatitis E virus, HIV Infections, Pre-Exposure Prophylaxis, Sexual and Gender Minorities
Abstract

Background: Men who have sex with men (MSM) have an increased risk of infection by pathogens transmitted by the oro-fecal route. Here, we investigated the seroprevalence and incidence of hepatitis E virus (HEV) infection in 416 MSM included in the ANRS IPERGAY PrEP trial., Results: Among the 62 (14.9% (95% CI: [11.6%-18.7%]) seropositive for HEV at inclusion, the only factor associated with testing seropositive for HEV was older age. Geographical origin, use of recreational drugs, number of sexual partners, status for HAV and bacterial sexually transmitted infection (STI) at inclusion were not associated. Among the 342 HEV-seronegative patients with available samples, 9 seroconverted after a median of follow-up of 2.1 years (IQR (interquartile range): [1.6; 3.0])., Conclusion: Overall, the HEV incidence was 1.19% per 100 person-years [95% CI: 0.54%; 2.26%]. Sexual transmission does not seem to be a major route of HEV infection in MSM, unlike HAV., Competing Interests: Declaration of Competing Interest No conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Published
2023
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40. Detection of SARS-CoV-2 in Saliva and Nasopharyngeal Swabs According to Viral Variants.

Author

Salmona M, Chaix ML, Feghoul L, Mahjoub N, Maylin S, Schnepf N, Jacquier H, Walle EM, Helary M, Mellon G, Osinski N, Zebiche W, Achili Y, Amarsy R, Mahé V, Le Goff J, and Delaugerre C

Subjects
Humans, SARS-CoV-2 genetics, Saliva, France, COVID-19 diagnosis
Abstract

The genome of the Omicron variant of concern (VOC) contains more than 50 mutations, many of which have been associated with increased transmissibility, differing disease severity, and the potential to elute immune responses acquired after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination or infection with previous VOCs. Due to a better tropism for the upper respiratory tract, it was suggested that the detection of the Omicron variant could be preferred in saliva, compared to nasopharyngeal swabs (NPS). Our objective was to compare the SARS-CoV-2 levels in saliva fluid and NPS to estimated Ct values, according to the main SARS-CoV-2 variants circulating in France since the beginning of 2021. We analyzed 1,289 positive reverse transcription-polymerase chain reaction (RT-PCR) results during the three major waves: Alpha, Delta, and Omicron. NPS and saliva sampling were performed for 909 (71%) and 380 (29%) cases, respectively. The Ct values were significantly lower in the NPS samples than in the saliva samples for the three main VOCs. Still, the difference was less pronounced with the Omicron variant than for the Alpha and Delta variants. In contrast, in the saliva samples, Ct values were significantly lower for the Omicron variant than for the Delta (difference of -2.7 Ct) and the Alpha (difference of -3.0 Ct) variants, confirming a higher viral load in saliva. To conclude, the higher viral load in saliva was evidenced for the Omicron variant, compared to the Alpha and Delta variants, suggesting that established diagnostic methods might require revalidation with the emergence of novel variants. IMPORTANCE Established methods for SARS-CoV-2 diagnostics might require revalidation with the emergence of novel variants. This is important for screening strategy programs and for the investigation of the characteristics of new variants in terms of tropism modification and increased viral burden leading to its spread. SARS-CoV-2 RT-PCR screening on saliva samples reported lower but acceptable performance, compared to nasopharyngeal samples. Due to a better tropism for the upper respiratory tract, it was suggested that the detection of the Omicron variant could be preferred in saliva, compared to nasopharyngeal swabs. Our study analyzed 1,289 positive RT-PCR results during the three major waves in France: Alpha, Delta, and Omicron. Our findings also showed a higher viral load in saliva for the Omicron variant, compared to the Alpha and Delta variants.

Published
2022
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41. Author Correction: Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19.

Author

de Prost N, Audureau E, Heming N, Gault E, Pham T, Chaghouri A, de Montmollin N, Voiriot G, Morand-Joubert L, Joseph A, Chaix ML, Préau S, Favory R, Guigon A, Luyt CE, Burrel S, Mayaux J, Marot S, Roux D, Descamps D, Meireles S, Pène F, Rozenberg F, Contou D, Henry A, Gaudry S, Brichler S, Timsit JF, Kimmoun A, Hartard C, Jandeaux LM, Fafi-Kremer S, Gabarre P, Emery M, Garcia-Sanchez C, Jochmans S, Pitsch A, Annane D, Azoulay E, Mekontso Dessap A, Rodriguez C, Pawlotsky JM, and Fourati S

Published
2022
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42. Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19.

Author

de Prost N, Audureau E, Heming N, Gault E, Pham T, Chaghouri A, de Montmollin N, Voiriot G, Morand-Joubert L, Joseph A, Chaix ML, Préau S, Favory R, Guigon A, Luyt CE, Burrel S, Mayaux J, Marot S, Roux D, Descamps D, Meireles S, Pène F, Rozenberg F, Contou D, Henry A, Gaudry S, Brichler S, Timsit JF, Kimmoun A, Hartard C, Jandeaux LM, Fafi-Kremer S, Gabarre P, Emery M, Garcia-Sanchez C, Jochmans S, Pitsch A, Annane D, Azoulay E, Mekontso Dessap A, Rodriguez C, Pawlotsky JM, and Fourati S

Subjects
Critical Illness, Humans, Phenotype, Prospective Studies, COVID-19, SARS-CoV-2 genetics
Abstract

Infection with SARS-CoV-2 variant Omicron is considered to be less severe than infection with variant Delta, with rarer occurrence of severe disease requiring intensive care. Little information is available on comorbid factors, clinical conditions and specific viral mutational patterns associated with the severity of variant Omicron infection. In this multicenter prospective cohort study, patients consecutively admitted for severe COVID-19 in 20 intensive care units in France between December 7th 2021 and May 1st 2022 were included. Among 259 patients, we show that the clinical phenotype of patients infected with variant Omicron (n = 148) is different from that in those infected with variant Delta (n = 111). We observe no significant relationship between Delta and Omicron variant lineages/sublineages and 28-day mortality (adjusted odds ratio [95% confidence interval] = 0.68 [0.35-1.32]; p = 0.253). Among Omicron-infected patients, 43.2% are immunocompromised, most of whom have received two doses of vaccine or more (85.9%) but display a poor humoral response to vaccination. The mortality rate of immunocompromised patients infected with variant Omicron is significantly higher than that of non-immunocompromised patients (46.9% vs 26.2%; p = 0.009). In patients infected with variant Omicron, there is no association between specific sublineages (BA.1/BA.1.1 (n = 109) and BA.2 (n = 21)) or any viral genome polymorphisms/mutational profile and 28-day mortality., (© 2022. The Author(s).)

Published
2022
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43. SARS-CoV-2 Genomic Characteristics and Clinical Impact of SARS-CoV-2 Viral Diversity in Critically Ill COVID-19 Patients: A Prospective Multicenter Cohort Study.

Author

Fourati S, Audureau E, Arrestier R, Marot S, Dubois C, Voiriot G, Luyt CE, Urbina T, Mayaux J, Roque-Afonso AM, Pham T, Landraud L, Visseaux B, Roux D, Bellaiche R, L'honneur AS, Ait Hamou Z, Brichler S, Gaudry S, Salmona M, Clere-Jehl R, Azoulay E, Morand-Joubert L, Marcelin AG, Chaix ML, Descamps D, Mekontso Dessap A, Rodriguez C, Pawlotsky JM, and de Prost N

Subjects
Adolescent, Adult, Critical Illness, Genomics, Humans, Prospective Studies, COVID-19, SARS-CoV-2 genetics
Abstract

The SARS-CoV-2 variant of concern, α, spread worldwide at the beginning of 2021. It was suggested that this variant was associated with a higher risk of mortality than other variants. We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 and unravel the relationships between specific viral mutations/mutational patterns and clinical outcomes. This is a prospective multicenter observational cohort study. Patients aged ≥18 years admitted to 11 intensive care units (ICUs) in hospitals in the Greater Paris area for SARS-CoV-2 infection and acute respiratory failure between 1 October 2020 and 30 May 2021 were included. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq). In total, 413 patients were included, 183 (44.3%) were infected with pre-existing variants, 197 (47.7%) were infected with variant α, and 33 (8.0%) were infected with other variants. The patients infected with pre-existing variants were significantly older (64.9 ± 11.9 vs. 60.5 ± 11.8 years; p = 0.0005) and had more frequent COPD (11.5% vs. 4.1%; p = 0.009) and higher SOFA scores (4 [3-8] vs. 3 [2-4]; 0.0002). The day-28 mortality was no different between the patients infected with pre-existing, α, or other variants (31.1% vs. 26.2% vs. 30.3%; p = 0.550). There was no association between day-28 mortality and specific variants or the presence of specific mutations. At ICU admission, the patients infected with pre-existing variants had a different clinical presentation from those infected with variant α, but mortality did not differ between these groups. There was no association between specific variants or SARS-CoV-2 genome mutational pattern and day-28 mortality.

Published
2022
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44. [Aspects virologiques, diagnostic et variants du SARS-CoV-2].

Author

Helary M, Salmona M, Walle ÉM, Feghoul L, Mahjoub N, Schnepf N, Maylin S, Chaix ML, Le Goff J, and Delaugerre C

Subjects
Antibodies, Viral, France, Humans, Spike Glycoprotein, Coronavirus genetics, Spike Glycoprotein, Coronavirus metabolism, COVID-19 diagnosis, SARS-CoV-2 genetics
Abstract

VIROLOGICAL ASPECTS, DIAGNOSTIC TOOLS AND VARIANTS OF SARS-COV-2 SARS-CoV-2 is an enveloped non-segmented linear single-stranded positive RNA virus. The envelope carries the protein spike (S) which recognizes the ACE2 receptor on the target cell and allows entry of the virus. The numerous mutations on the S protein are at the origin of a great genetic diversity, involved in the species barrier and the escape from neutralizing antibodies. The main mode of transmission is respiratory. The virus replicates 24 hours after infection and the viral RNA is detected by direct diagnostic techniques as the reference technique is RT-PCR on a nasopharyngeal sample. To expand screening, RT-PCR on saliva samples and antigenic tests have been developed. The majority of patients develop specific antibodies within 10-15 days which are detectable by serological methods. It is recommended to combine the search for anti-N and anti-S antibodies. The viral genome has great plasticity and variants emerged from the summer of 2020. There are several classifications, including that of the WHO, which assigns each variant a Greek letter. Finally, Santé publique France has deployed an epidemiological surveillance system of variants using PCR screening and sequencing., Competing Interests: M. Helary, M. Salmona, E.-M. Walle, L. Feghoul, N. Mahjoub, N. Schnepf, S. Maylin, M.-L. Chaix et J. Le Goff déclarent n’avoir aucun lien d’intérêts. - C. Delaugerre déclare des liens d’intérêts avec ViiV, MSD, Gilead.

Published
2022

45. HIV-1 RNA Kinetics in Blood Plasma and in Seminal Plasma of Men Starting a Dolutegravir-Based Triple-Combination Regimen at the Time of Primary HIV-1 Infection.

Author

Ghosn J, Assoumou L, Lascoux-Combe C, Peytavin G, Amat K, Gabassi A, Le MP, Nzalakanda R, Valin N, Landman R, Chaix ML, and Delaugerre C

Subjects
Adult, HIV Infections genetics, Humans, Kinetics, Male, Middle Aged, RNA, Viral genetics, Viral Load, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1 genetics, Heterocyclic Compounds, 3-Ring therapeutic use, Oxazines therapeutic use, Piperazines therapeutic use, Pyridones therapeutic use, Semen virology
Abstract

We compared the proportion of participants achieving first undetectable HIV-1 RNA (VL) in seminal plasma (SP) and blood plasma (BP) in 19 men starting dolutegravir-based regimen at primary HIV infection. At baseline, median VL was 6.5 (interquartile range [IQR], 5.6-7.9) and 4.5 (IQR, 3.5-5.0) log10 copies/mL in BP and SP, respectively. Between baseline and week 48, significantly higher proportion of participants achieved first VL below limit of quantification in SP (93.0%) than in BP (84.2%; P = .008). Time to first undetectable VL was 8 weeks in SP (95% confidence interval [CI], 5.6-10.4) and 24 weeks in BP (95% CI, 14.1-33.9)., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Published
2022
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46. Performance of 30 commercial SARS-CoV-2 serology assays in testing symptomatic COVID-19 patients.

Author

Vauloup-Fellous C, Maylin S, Périllaud-Dubois C, Brichler S, Alloui C, Gordien E, Rameix-Welti MA, Gault E, Moreau F, Fourati S, Challine D, Pawlotsky JM, Houhou-Fidouh N, Damond F, Mackiewicz V, Charpentier C, Méritet JF, Rozenberg F, Podglajen I, Marot S, Petit H, Burrel S, Akhavan S, Leruez-Ville M, Avettand-Fenoel V, Fourgeaud J, Guilleminot T, Gardiennet E, Bonacorsi S, Carol A, Carcelain G, Villemonteix J, Boukli N, Gozlan J, Morand-Joubert L, Legoff J, Delaugerre C, Chaix ML, Roque-Afonso AM, Dortet L, Naas T, Ronat JB, Lepape S, Marcelin AG, and Descamps D

Subjects
COVID-19 virology, Humans, Immunoassay economics, Immunoglobulin M blood, Reagent Kits, Diagnostic, SARS-CoV-2 genetics, SARS-CoV-2 isolation & purification, Sensitivity and Specificity, Antibodies, Viral blood, COVID-19 blood, COVID-19 Serological Testing methods, Immunoassay methods, SARS-CoV-2 immunology
Abstract

We report evaluation of 30 assays' (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2021
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47. Virological failure and drug resistance in West African HIV-infected adults who started ART immediately or deferred ART initiation.

Author

Gabillard D, N'Takpé JB, Chaix ML, Kouame GM, Moh R, Toni TD, Le Carrou J, Karcher S, Badje A, Emieme A, Menan H, Danel C, Anglaret X, and Eholié SP

Subjects
Adult, CD4 Lymphocyte Count, Drug Resistance, Humans, Viral Load, World Health Organization, Anti-HIV Agents therapeutic use, HIV Infections drug therapy
Abstract

Background: Asymptomatic HIV-infected people who start ART early may feel less motivated and neglect compliance. This might promote the emergence of resistance., Methods: In the Temprano trial, ART-naive HIV-infected adults with high CD4 counts were randomly assigned to start ART immediately (immediate group) or defer ART until the WHO criteria were met (deferred group). All participants were monitored for 30 months. Those in the deferred group who started ART were monitored for longer, until they had completed 30 months on ART. We compared the rate of virological failure and drug resistance between the immediate and deferred groups 30 months after ART initiation., Results: Of the 2056 participants in Temprano, 1033 were assigned to start ART immediately and 1023 to defer ART. Of the latter, 488 started ART during trial follow-up. Patients in the deferred group who started ART had a lower median CD4 count (280 versus 465 cells/mm3) and a higher median plasma HIV-1 RNA (5.1 versus 4.7 log10 copies/mL) at baseline. During follow-up, participants in both groups had similar antiretroviral drug exposure. Thirty months after ART initiation, patients in the deferred group had a higher rate of virological failure (35.3% versus 29.9%, P = 0.04) and a lower genotypic susceptibility score (P = 0.04)., Conclusions: Starting ART early decreases the risk of virological failure and drug resistance in the medium term. This benefit is of particular importance in countries where access to viral load monitoring and the number of antiretroviral drug lines is limited., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2021
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48. Factors associated with the emergence of integrase resistance mutations in patients failing dual or triple integrase inhibitor-based regimens in a French national survey.

Author

Marcelin AG, Charpentier C, Bellecave P, Abdi B, Chaix ML, Ferre V, Raymond S, Fofana D, Bocket L, Mirand A, Le Guillou-Guillemette H, Montes B, Amiel C, Pallier C, Fafi-Kremer S, De Monte A, Alessandri-Gradt E, Scholtes C, Maillard A, Jeulin H, Bouvier-Alias M, Roussel C, Dos Santos G, Signori-Schmuck A, Dina J, Vallet S, Stefic K, Soulié C, Calvez V, Descamps D, and Flandre P

Subjects
Drug Resistance, Viral genetics, Heterocyclic Compounds, 3-Ring therapeutic use, Humans, Mutation, Pyridones, Raltegravir Potassium therapeutic use, HIV Infections drug therapy, HIV Integrase genetics, HIV Integrase Inhibitors pharmacology, HIV Integrase Inhibitors therapeutic use, HIV-1 genetics
Abstract

Background: Successful 2-drug regimens (2DRs) for HIV were made possible by the availability of drugs combining potency and tolerability with a high genetic barrier to resistance. How these deal with resistance development/re-emergence, compared with 3DRs, is thus of paramount importance., Materials and Methods: A national survey including patients who were either naive or experienced with any 2DR or 3DR but failing integrase strand transfer inhibitor (INSTI)-containing regimens [two consecutive plasma viral load (VL) values >50 copies/mL] was conducted between 2014 and 2019. Genotypic resistance tests were interpreted with the v28 ANRS algorithm., Results: Overall, 1104 patients failing any INSTI-containing regimen (2DRs, n = 207; 3DRs, n = 897) were analysed. Five hundred and seventy-seven (52.3%) patients were infected with a B subtype and 527 (47.3%) with non-B subtypes. Overall, 644 (58%) patients showed no known integrase resistance mutations at failure. In multivariate analysis, factors associated with the emergence of at least one integrase mutation were: high VL at failure (OR = 1.24 per 1 log10 copies/mL increase); non-B versus B subtype (OR = 1.75); low genotypic sensitivity score (GSS) (OR = 0.10 for GSS = 2 versus GSS = 0-0.5); and dolutegravir versus raltegravir (OR = 0.46). Although 3DRs versus 2DRs reached statistical significance in univariate analysis (OR = 0.59, P = 0.007), the variable is not retained in the final model., Conclusions: This study is one of the largest studies characterizing integrase resistance in patients failing any INSTI-containing 2DR or 3DR in routine clinical care and reveals factors associated with emergence of integrase resistance that should be taken into consideration in clinical management. No difference was evidenced between patients receiving a 2DR or a 3DR., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2021
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49. Interpretation of single target positivity among SARS-CoV-2 RT-PCR result tests.

Author

Fenaux H, Ghelfenstein-Ferreira T, Salmona M, Mahjoub N, Feghoul L, Maylin S, Chaix ML, Minier M, Gabassi A, Goff JL, and Delaugerre C

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged and is responsible for coronavirus disease 19 (COVID-19). Diagnostic tests have been developed, mainly based on reverse-transcriptase PCR (RT-PCR). Most RT-PCR assays target at least two SARS-CoV-2 genes. In some cases, only one target gene is detected; the interpretation of such cases remains unclear., Objectives: Our objective was to analyse one target positive (OPT) RT-PCR results, using two RT-PCR assays: the Xpert® Xpress SARS-CoV-2 (Cepheid diagnosis, "Cepheid") and the Cobas® 6800 SARS-CoV-2 Test (Roche Molecular Diagnostics, "Roche")., Methods: All SARS-CoV-2 RT-PCR results performed on respiratory samples with the Roche or the Cepheid tests, from 23rd March to 6th August 2020 were collected. A patient with an OPT result was classified as "probable COVID-19" if they met at least one of the three following criteria: (i) history of a two gene-positive SARS-CoV-2 RT-PCR result, (ii) anti-SARS-CoV-2 antibody (IgG) detection or (iii) compatible chest computed tomography scan (CT-scan)., Results: A total of 18,630 and 1189 SARS-CoV-2 RT-PCR tests were performed with the Roche and Cepheid tests, respectively. Among the positive SARS-CoV-2 RT-PCR, 293 samples - corresponding to 264 patients - were OPT (11% of the positive samples). Of these patients, 180 (68%) had at least one of the three criteria listed above and were classified as probable COVID-19., Conclusions: Sixty-eight percent of the patients with an OPT result were classified as probable COVID-19 and are probably at a late stage of infection. Serology and imaging can be helpful to confirm diagnosis., Competing Interests: None., (© 2021 The Author(s).)

Published
2021
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50. Deep sequencing analysis of M184V/I mutation at the switch and at the time of virological failure of boosted protease inhibitor plus lamivudine or boosted protease inhibitor maintenance strategy (substudy of the ANRS-MOBIDIP trial).

Author

Delaugerre C, Nere ML, Eymard-Duvernay S, Armero A, Ciaffi L, Koulla-Shiro S, Sawadogo A, Ngom Gueye NF, Ndour CT, Mpoudi Ngolle M, Amara A, Chaix ML, and Reynes J

Subjects
Drug Resistance, Viral, High-Throughput Nucleotide Sequencing, Humans, Lamivudine therapeutic use, Mutation, Protease Inhibitors therapeutic use, Viral Load, Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1 genetics
Abstract

Background: The ANRS12286/MOBIDIP trial showed that boosted protease inhibitor (bPI) plus lamivudine dual therapy was superior to bPI monotherapy as maintenance treatment in subjects with a history of M184V mutation., Objectives: We aimed to deep analyse the detection of M184V/I variants at time of switch and at the time of virological failure (VF)., Methods: Ultra-deep sequencing (UDS) was performed on proviral HIV-DNA at inclusion among 265 patients enrolled in the ANRS 12026/MOBIDIP trial, and on plasma from 31 patients experiencing VF. The proportion of M184V/I variants was described and the association between the M184V/I mutation at 1% of threshold and VF was explored with logistic regression models., Results: M184V and I mutations were detected in HIV-DNA for 173/252 (69%) and 31/252 (12%) of participants, respectively. Longer duration of first-line treatment, higher plasma viral load at first-line treatment failure and higher baseline HIV-DNA load were associated with the archived M184V. M184I mutation was always associated with a STOP codon, suggesting defective virus. The 48 week estimated probability of remaining free from VF was comparable with or without the M184V/I mutation for dual therapy. At failure, M184V and major PI mutations were detected in 1/17 and 5/15 patients in the bPI arm and in 2/2 and 0/3 in the bPI+lamivudine arm, respectively., Conclusions: Using UDS evidenced that archiving of M184V in HIV-DNA is heterogeneous despite past historical M184V in 96% of cases. The antiviral efficacy of lamivudine-based dual therapy regimens is mainly due to the residual lamivudine activity., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2021
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