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3. 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

4. Comparison of short‐read and long‐read next‐generation sequencing technologies for determining HIV‐1 drug resistance.

Author

Vellas, Camille, Doudou, Amira, Mohamed, Sofiane, Raymond, Stéphanie, Jeanne, Nicolas, Latour, Justine, Demmou, Sofia, Ranger, Noémie, Gonzalez, Dimitri, Delobel, Pierre, and Izopet, Jacques

Subjects
WHOLE genome sequencing, REVERSE transcriptase, NUCLEOTIDE sequencing, RNA sequencing, DNA sequencing
Abstract

Accurate HIV‐1 genome sequencing is necessary to identify drug resistance mutations (DRMs) in people with HIV‐1 (PWH). Next‐generation‐sequencing (NGS) allows the detection of minor variants and is now available in many laboratories. Our study aimed to compare two NGS approaches, a "short read" sequencing protocol using DeepChek® Whole Genome HIV‐1 Assay on Illumina, and a "long read" sequencing protocol of HIV‐1 pol and env single‐molecule real‐time sequencing (SMRT) on Pacific Biosciences (PacBio). We analyzed 16 plasma samples and 13 cellular samples from PWH. HIV‐1 whole genome was amplified into five amplicons using DeepChek® Whole Genome HIV‐1 Assay and sequenced on an iSeq. 100. In parallel, HIV‐1 pol and env genes were separately amplified and sequenced using PacBio SMRT system with the circular consensus sequencing mode on a Sequel IIe. Concordance rates for determining DRMs with both approaches varied depending on the HIV‐1 region, with higher concordance in the integrase region compared to the reverse transcriptase and protease regions. DeepChek® Whole Genome HIV‐1 Assay exhibited better sensitivity in HIV‐1 RNA sequencing of plasmas with lower viral loads. In cell HIV‐1 DNA sequencing, the DeepChek® Whole Genome HIV‐1 Assay performed better in pol and env sequencing but detected more APOBEC‐induced DRMs, which can represent defective proviruses. Our findings indicate that both DeepChek® Whole Genome HIV‐1 Assay and PacBio SMRT sequencing exhibit good performance for subtype determination, detection, and quantification of DRMs of the HIV‐1 genome. However, some discrepancies were found in cellular samples, highlighting the challenges of interpreting HIV‐1 DNA DRMs. [ABSTRACT FROM AUTHOR]

Published
2024
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5. 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, 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, Avettand Fenoel, Véronique, Roussel, Catherine, Calvez, Vincent, Saune, Karine, Marcelin, Anne, Rodriguez, Christophe, Descamps, Diane, and Izopet, Jacques

Subjects
Adult, Drug Resistance, Viral, Female, Genetic Variation, HIV Infections, HIV-1, Humans, Male, Mutation, Rilpivirine, Viral Load
Abstract

BACKGROUND: Minority resistant variants of human immunodeficiency virus type 1 (HIV-1) could influence the virological response to treatment based on nonnucleoside reverse transcriptase inhibitors (NNRTIs). Data on minority rilpivirine-resistant variants are scarce. This study used next-generation sequencing (NGS) to identify patients harboring minority resistant variants to nucleos(t)ide reverse transcriptase inhibitors and NNRTIs and to assess their influence on the virological response (VR). METHODS: All the subjects, 541 HIV-1-infected patients started a first-line regimen containing rilpivirine. VR was defined as a HIV-1 RNA load 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

7. DORAVIR: a French national survey of people with HIV-1 treated with an antiretroviral regimen including doravirine.

Author

Soulie, Cathia, Balde, Aliou, Fofana, Djeneba, Charpentier, Charlotte, Bonnafous, Pascale, Sourice, Justine, Monte, Anne De, Avettand-Fenoel, Véronique, Guillou-Guillemette, Hélène Le, Bocket, Laurence, Raymond, Stéphanie, Juillet, Stéphanie Marque, Trabaud, Mary-Anne, Montes, Brigitte, Maillard, Anne, Hartard, Cédric, Alessandri-Gradt, Elodie, Brochot, Etienne, Signori-Schmuck, Anne, and Assoumou, Lambert

Subjects
VIRAL load, ANTIRETROVIRAL agents, HIV, GENOTYPES, RALTEGRAVIR, RNA
Abstract

Background Doravirine is the latest NNRTI to be approved for the treatment of HIV-1 and has a different resistance profile from first-generation NNRTIs. Our aim was to investigate the virological efficacy of antiretroviral treatment including doravirine in people living with HIV-1 (PLWHIV), the factors associated with virological failure (VF) and those associated with the emergence of reverse transcriptase (RT) mutations in the case of VF. Methods A retrospective national survey of PLWHIV who were either naive or experienced on antiretroviral treatment including doravirine was conducted. VF was defined as two consecutive plasma viral loads (VLs) of ≥50 copies/mL or one VL of ≥200 copies/mL. Genotypic resistance tests were interpreted using the Stanford (v9.4.1) and ANRS (v33) algorithms. Results Of the 589 PLWHIV treated with a doravirine-containing regimen, 8.5% were naive and 91.5% had prior antiretroviral experience; 56.9% were infected with HIV-1 B subtype. Overall, 88.3% and 85.1% of participants were virologically controlled at Month (M)3 and M6 of doravirine treatment, respectively. In multivariable analysis, CRF02_AG subtype, higher zenith plasma HIV-1 RNA VL, doravirine initiation in the context of failure and baseline V179D mutation presence were associated with VF. Among 88 PLWHIV who experienced virological failure at M6, 15.9% had a median of 2 (IQR 1–3) HIV RT mutations. In multivariable analysis, the only factor associated with the occurrence of mutations was a genotypic sensitivity score that was not fully sensitive. Conclusions This study is one of the largest to characterize the virological efficacy of doravirine-containing regimens in clinical practice and to identify factors associated with VF or emergence of resistance mutations that should be considered in clinical management. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma.

Author

Soulie, Cathia, Descamps, Diane, Grudé, Maxime, Schneider, Véronique, Trabaud, Mary-Anne, Morand-Joubert, Laurence, Delaugerre, Constance, Montes, Brigitte, Barin, Francis, Ferre, Virginie, Raymond, Stéphanie, Jeulin, Hélène, Alloui, Chakib, Yerly, Sabine, Pallier, Coralie, Reigadas, Sandrine, Signori-Schmuck, Anne, Guigon, Aurélie, Fafi-Kremer, Samira, Haïm-Boukobza, Stéphanie, Mirand, Audrey, Maillard, Anne, Vallet, Sophie, Roussel, Catherine, Assoumou, Lambert, Calvez, Vincent, Flandre, Philippe, Marcelin, Anne-Geneviève, and ANRS Resistance AC11 Group

Subjects
ANRS Resistance AC11 Group, Humans, HIV-1, HIV Infections, Nervous System Diseases, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Microbial Sensitivity Tests, Viral Load, Drug Resistance, Viral, Genotype, Mutation, Adult, Middle Aged, Female, Male, ARV, CSF, HIV, resistance, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, Microbiology, Medical Microbiology, 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

11. HPV genotyping in clinical samples using long‐read single‐molecule real‐time sequencing.

Author

Pasquier, Christophe, Raymond, Stéphanie, Carcenac, Romain, Demmou, Sofia, Ranger, Noémie, Nicot, Florence, and Izopet, Jacques

Subjects
HUMAN papillomavirus, EARLY detection of cancer, SINGLE molecules
Abstract

Human papillomavirus (HPV) genotyping is widely used, particularly in combination with high‐risk (HR) HPV tests for cervical cancer screening. We developed a genotyping method using sequences of approximately 800 bp in the E6/E7 region obtained by PacBio single molecule real‐time sequencing (SMRT) and evaluated its performance against MY09‐11 L1 sequencing and after the APTIMA HPV genotyping assay. The levels of concordance of PacBio E6/E7 SMRT sequencing with MY09‐11 L1 sequencing and APTIMA HPV genotyping were 100% and 90.8%, respectively. The sensitivity of PacBio E6/EA7 SMRT was slightly greater than that of L1 sequencing and, as expected, lower than that of HR‐HPV tests. In the context of cervical cancer screening, PacBio E6/E7 SMRT is then best used after a positive HPV test. PacBio E6/E7 SMRT genotyping is an attractive alternative for HR and LR‐HPV genotyping of clinical samples. PacBio SMRT sequencing provides unbiased genotyping and can detect multiple HPV infections and haplotypes within a genotype. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Impact of Human Immunodeficiency Virus Type 1 Minority Variants on the Virus Response to a Rilpivirine-Based First-line Regimen

Author

French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group, 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, and Izopet, Jacques

Published
2018

22. Influence of Nasopharyngeal Viral Load on the Spread of the Omicron BA.2 Variant

Author

Migueres, Marion, primary, Dimeglio, Chloé, additional, Mansuy, Jean Michel, additional, Abravanel, Florence, additional, Raymond, Stéphanie, additional, Latour, Justine, additional, Jeanne, Nicolas, additional, Ranger, Noémie, additional, Lhomme, Sébastien, additional, Saune, Karine, additional, Tremeaux, Pauline, additional, and Izopet, Jacques, additional

Published
2022
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24. Influence of the Delta Variant and Vaccination on the SARS-CoV-2 Viral Load

Author

Migueres, Marion, primary, Dimeglio, Chloé, additional, Trémeaux, Pauline, additional, Raymond, Stéphanie, additional, Lhomme, Sébastien, additional, Da Silva, Isabelle, additional, Oliveira Mendes, Kévin, additional, Abravanel, Florence, additional, Félicé, Marie-Pierre, additional, Mansuy, Jean-Michel, additional, and Izopet, Jacques, additional

Published
2022
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26. HIV-1 resistance genotyping by ultra-deep sequencing and 6-month virological response to first-line treatment.

Author

Raymond, Stéphanie, Jeanne, Nicolas, Nicot, Florence, Dimeglio, Chloé, Carcenac, Romain, Harter, Agnès, Ranger, Noémie, Martin-Blondel, Guillaume, Delobel, Pierre, and Izopet, Jacques

Subjects
*RALTEGRAVIR, *REVERSE transcriptase inhibitors, *ANTI-HIV agents, *ANTIRETROVIRAL agents, *INTEGRASE inhibitors, *DRUG resistance, *HIV, *HEPATITIS C virus
Abstract

Objectives: To evaluate the routine use of the Sentosa ultra-deep sequencing (UDS) system for HIV-1 polymerase resistance genotyping in treatment-naïve individuals and to analyse the virological response (VR) to first-line antiretroviral treatment.Methods: HIV drug resistance was determined on 237 consecutive samples from treatment-naïve individuals using the Sentosa UDS platform with two mutation detection thresholds (3% and 20%). VR was defined as a plasma HIV-1 virus load <50 copies/mL after 6 months of treatment.Results: Resistance to at least one antiretroviral drug with a mutation threshold of 3% was identified in 29% and 16% of samples according to ANRS and Stanford algorithms, respectively. The ANRS algorithm also revealed reduced susceptibility to at least one protease inhibitor (PI) in 14.3% of samples, to one reverse transcriptase inhibitor in 12.7%, and to one integrase inhibitor (INSTI) in 5.1%. For a mutation threshold of 20%, resistance was identified in 24% and 13% of samples according to ANRS and Stanford algorithms, respectively. The 6 months VR was 87% and was similar in the 58% of patients given INSTI-based treatment, in the 16% given PI-based treatment and in the 9% given NNRTI-based treatment. Multivariate analysis indicated that the VR was correlated with the baseline HIV virus load and resistance to at least one PI at both 3% and 20% mutation detection thresholds (ANRS algorithm).Conclusions: The Vela UDS platform is appropriate for determining antiretroviral resistance in patients on a first-line antiretroviral treatment. Further studies are needed on the use of UDS for therapeutic management. [ABSTRACT FROM AUTHOR]

Published
2023
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27. Influence of Nasopharyngeal Viral Load on the Spread of the Omicron BA.2 Variant.

Author

Migueres, Marion, Dimeglio, Chloé, Mansuy, Jean-Michel, Abravanel, Florence, Raymond, Stéphanie, Latour, Justine, Jeanne, Nicolas, Ranger, Noémie, Lhomme, Sébastien, Saune, Karine, Tremeaux, Pauline, and Izopet, Jacques

Subjects
NASOPHARYNX microbiology, COVID-19, VIRAL load, DESCRIPTIVE statistics, POLYMERASE chain reaction, FRIEDMAN test (Statistics)
Abstract

We used variant typing polymerase chain reaction to describe the evolution of severe acute respiratory syndrome coronavirus 2 Omicron sublineages between December 2021 and mid-March 2022. The selective advantage of the BA.2 variant over BA.1 is not due to greater nasopharyngeal viral loads. [ABSTRACT FROM AUTHOR]

Published
2023
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28. Whole‐genome sequencing of SARS‐CoV‐2: Comparison of target capture and amplicon single molecule real‐time sequencing protocols.

Author

Nicot, Florence, Trémeaux, Pauline, Latour, Justine, Jeanne, Nicolas, Ranger, Noémie, Raymond, Stéphanie, Dimeglio, Chloé, Salin, Gérald, Donnadieu, Cécile, and Izopet, Jacques

Subjects
SARS-CoV-2, NUCLEOTIDE sequencing, SINGLE molecules
Abstract

Fast, accurate sequencing methods are needed to identify new variants and genetic mutations of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) genome. Single‐molecule real‐time (SMRT) Pacific Biosciences (PacBio) provides long, highly accurate sequences by circular consensus reads. This study compares the performance of a target capture SMRT PacBio protocol for whole‐genome sequencing (WGS) of SARS‐CoV‐2 to that of an amplicon PacBio SMRT sequencing protocol. The median genome coverage was higher (p < 0.05) with the target capture protocol (99.3% [interquartile range, IQR: 96.3–99.5]) than with the amplicon protocol (99.3% [IQR: 69.9–99.3]). The clades of 65 samples determined with both protocols were 100% concordant. After adjusting for Ct values, S gene coverage was higher with the target capture protocol than with the amplicon protocol. After stratification on Ct values, higher S gene coverage with the target capture protocol was observed only for samples with Ct > 17 (p < 0.01). PacBio SMRT sequencing protocols appear to be suitable for WGS, genotyping, and detecting mutations of SARS‐CoV‐2. [ABSTRACT FROM AUTHOR]

Published
2023
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29. Virological failure of patients on maraviroc-based antiretroviral therapy

Author

Raymond, Stéphanie, Maillard, Anne, Amiel, Corinne, Peytavin, Gilles, Trabaud, Mary Anne, Desbois, Delphine, Bellecave, Pantxika, Delaugerre, Constance, Soulie, Cathia, Marcelin, Anne Geneviève, Descamps, Diane, Izopet, Jacques, Reigadas, S., Bellecave, P., Pinson-Recordon, P., Fleury, H., Masquelier, B., Signori-Schmuck, A., Morand, P., Bocket, L., Mouna, L., André, P., Tardy, J. C., Trabaud, M. A., Descamps, D., Charpentier, C., Peytavin, G., Brun-Vézinet, F., Haim-Boukobza, S., Roques, A. M., Soulié, C., Lambert-Niclot, S., Malet, I., Wirden, M., Fourati, S., Marcelin, A. G., Calvez, V., Flandre, P., Assoumou, L., Costagliola, D., Morand-Joubert, L., Delaugerre, C., Schneider, V., Amiel, C., Giraudeau, G., Maillard, A., Nicot, F., and Izopet, J.

Published
2015
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35. Setting the agenda for social science research on the human microbiome

Author

Roberts, Adam, Raymond, Stéphanie, Podolsky, Scott, Outterson, Kevin, Nayiga, Susan, Hoffman, Steven, Hinchliffe, Stephen, Gradmann, Christoph, Frost, Isabel, Pinto Ferreira, Jorge, Chuengsatiansup, Komatra, Broom, Alex, Atkinson, Paul, Greenhough, Beth, Read, Cressida, Lorimer, Jamie, Lezaun, Javier, Mcleod, Carmen, Benezra, Amber, Bloomfield, Sally, Brown, Tim, Clinch, Megan, D’acquisto, Fulvio, Dumitriu, Anna, Evans, Joshua, Fawcett, Nicola, Fortané, Nicolas, Hall, Lindsay, Giraldo Herrera, César, Hodgetts, Timothy, Johnson, Katerina Vicky-Ann, Kirchhelle, Claas, Krzywoszynska, Anna, Lambert, Helen, Monaghan, Tanya, Nading, Alex, Nerlich, Brigitte, Singer, Andrew, Szymanski, Erika, Wills, Jane, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Recherche Interdisciplinaire en Sciences Sociales (IRISSO), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Oxford Interdisciplinary Microbiome Project (IMP)John Fell FundUK Research & Innovation (UKRI)Economic & Social Research Council (ESRC)ES/N006968/1

Subjects
medical humanities, education, 0507 social and economic geography, Public policy, geography, [SHS]Humanities and Social Sciences, lcsh:Social Sciences, antibiotique, 03 medical and health sciences, Empirical research, anthropology, Medical humanities, Microbiome, Public engagement, General Psychology, agriculture, 030304 developmental biology, 0303 health sciences, sociologie, business.industry, science, technology and society, General Arts and Humanities, 05 social sciences, Social change, General Social Sciences, Public relations, Private sector, lcsh:H, Environmental governance, Health, history, business, 050703 geography, General Economics, Econometrics and Finance
Abstract

The human microbiome is an important emergent area of cross, multi and transdisciplinary study. The complexity of this topic leads to conflicting narratives and regulatory challenges. It raises questions about the benefits of its commercialisation and drives debates about alternative models for engaging with its publics, patients and other potential beneficiaries. The social sciences and the humanities have begun to explore the microbiome as an object of empirical study and as an opportunity for theoretical innovation. They can play an important role in facilitating the development of research that is socially relevant, that incorporates cultural norms and expectations around microbes and that investigates how social and biological lives intersect. This is a propitious moment to establish lines of collaboration in the study of the microbiome that incorporate the concerns and capabilities of the social sciences and the humanities together with those of the natural sciences and relevant stakeholders outside academia. This paper presents an agenda for the engagement of the social sciences with microbiome research and its implications for public policy and social change. Our methods were informed by existing multidisciplinary science-policy agenda-setting exercises. We recruited 36 academics and stakeholders and asked them to produce a list of important questions about the microbiome that were in need of further social science research. We refined this initial list into an agenda of 32 questions and organised them into eight themes that both complement and extend existing research trajectories. This agenda was further developed through a structured workshop where 21 of our participants refined the agenda and reflected on the challenges and the limitations of the exercise itself. The agenda identifies the need for research that addresses the implications of the human microbiome for human health, public health, public and private sector research and notions of self and identity. It also suggests new lines of research sensitive to the complexity and heterogeneity of human–microbiome relations, and how these intersect with questions of environmental governance, social and spatial inequality and public engagement with science.

Published
2020

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

Author

Raymond, Stéphanie, Recordon-Pinson, Patricia, Saliou, Adrien, Delobel, Pierre, Nicot, Florence, Descamps, Diane, Marcelin, Anne-Geneviève, Flandre, Philippe, Calvez, Vincent, Masquelier, Bernard, Izopet, Jacques, Recordon-Pinson, P., Fleury, H., Masquelier, B., Vabret, A., Pallier, C., Lazrek, M, André, P., Tardy, J. C., Trabaud, M. A., Tamalet, C., Montes, B., Segondy, M., Ferré, V., Cottalorda, J., Macé, M., Descamps, D., Brun-Vézinet, F., Si-Mohammed, A., Charpentier, C., Desbois, D., Dussaix, E., Marcelin, A. G., Soulié, C., Calvez, V., Flandre, F., Morand-Joubert, L., Amiel, C., Schneider, V., Maillard, A., Ruffault, A., Izopet, J., Nicot, F., Delobel, P., and Raymond, S.

Published
2011
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45. Surveillance of HIV-1 primary infections in France from 2014 to 2016: toward stable resistance, but higher diversity, clustering and virulence?

Author

Visseaux, Benoit, Assoumou, Lambert, Grude, Maxime, Carles, Marie-Josée, Meyer, Laurence, Roussel, Catherine, Le Guillou-Guillemette, H., Ducancelle, A., Courdavault, L, Alloui, C, Honore, P, Lepiller, Q., Bettinger, D., Bellecave, P., Pinson-Recordon, P, Tumiotto, Camille, Vallet, Sophie, Payan, C., Duthe, J, Leroux, M., Dina, Julia, Vabret, A., Mirand, A., Henquell, C., Bouvier-Alias, Magali, Simohamed, A, dos Santos, G, yerly, S, Gaille, C, Caveng, W, Chapalay, S, Calmy, A., Signori-Schmuck, Anne, Morand, Patrice, Pallier, Coralie, Raho-Moussa, M, Mole, M, Dulucq, M-J, Bocket, Laurence, Alidjinou, K, Ranger-Rogez, S, Trabaud, Mary-Anne, Icard, V, Tardy, J., Tamalet, C., Delamare, C, Montes, Brigitte, Schvoerer, E., Fenaux, H., Rodallec, A., André-Garnier, E., Ferre, Virginie, de Monte, Anne, Guigon, A., Guinard, J., Descamps, Diane, Charpentier, C., Peytavin, G., Tremaux, P, Avettand-Fenoel, V., Soulie, C., Malet, I., Wirden, Marc, Marcelin, A, Calvez, V., Flandre, P., Costagliola, D, Morand-Joubert, Laurence, Lambert-Niclot, S., Fofana, D, Boukli, N., Delaugerre, C., Chaix, Marie-Laure, Mahjoub, Nadia, Amiel, Corinne, Giraudeau, G, Beby-Defaux, A., Plainchamp, D, Maillard, Anne, Alessandri-Gradt, E, Leoz, M, Plantier, Jean-Christophe, Gantner, P, Delagreverie, H, Fafi-Kremer, Samira, Fischer, P, Raymond, Stéphanie, Izopet, Jacques, Chiabrando, J, Stefic, Karl, Barin, F., Fajole, G, Burgault, O, Marque-Juillet, S, Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), virology, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de recherche sur l'hétéroepitaxie et ses applications (CRHEA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Clermont-Ferrand, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Geneva University Hospital (HUG), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de virologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôtel-Dieu de Nantes, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Pharmacie de l'Hôpital Bichat, Centre de Recherches Pétrographiques et Géochimiques (CRPG), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Service de microbiologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Unité de Rétrovirologie, Hôpital Pontchaillou, Normandie Université (NU), Laboratoire de Virologie, CHU Strasbourg, Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Centre national de référence du VIH INSERM U966, Université de Tours (UT), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Besançon, Université de Franche-Comté (UFC), Université Grenoble Alpes (UGA), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU AMU), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université de Tours, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
Male, Etravirine, HIV Infections, Men who have sex with men, Sexual and Gender Minorities, chemistry.chemical_compound, Pre-exposure prophylaxis, 0302 clinical medicine, Pharmacology (medical), 030212 general & internal medicine, Phylogeny, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, education.field_of_study, Virulence, biology, [SDE.IE]Environmental Sciences/Environmental Engineering, Middle Aged, Viral Load, 3. Good health, Integrase, Infectious Diseases, Rilpivirine, Epidemiological Monitoring, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, France, Viral load, medicine.drug, Adult, Microbiology (medical), Genotype, Anti-HIV Agents, [SDE.MCG]Environmental Sciences/Global Changes, Population, Evolution, Molecular, 03 medical and health sciences, Drug Resistance, Viral, medicine, Humans, education, Pharmacology, 030306 microbiology, Genetic Variation, Sequence Analysis, DNA, [SDE.ES]Environmental Sciences/Environmental and Society, Virology, chemistry, Mutation, HIV-1, biology.protein, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract

ObjectivesPatients with primary HIV-1 infection (PHI) are a particular population, giving important insight about ongoing evolution of transmitted drug resistance-associated mutation (TDRAM) prevalence, HIV diversity and clustering patterns. We describe these evolutions of PHI patients diagnosed in France from 2014 to 2016.MethodsA total of 1121 PHI patients were included. TDRAMs were characterized using the 2009 Stanford list and the French ANRS algorithm. Viral subtypes and recent transmission clusters (RTCs) were also determined.ResultsPatients were mainly MSM (70%) living in the Paris area (42%). TDRAMs were identified among 10.8% of patients and rose to 18.6% when including etravirine and rilpivirine TDRAMs. Prevalences of PI-, NRTI-, first-generation NNRTI-, second-generation NNRTI- and integrase inhibitor-associated TDRAMs were 2.9%, 5.0%, 4.0%, 9.4% and 5.4%, respectively. In a multivariable analysis, age >40 years and non-R5 tropic viruses were associated with a >2-fold increased risk of TDRAMs. Regarding HIV diversity, subtype B and CRF02_AG (where CRF stands for circulating recombinant form) were the two main lineages (56% and 20%, respectively). CRF02_AG was associated with higher viral load than subtype B (5.83 versus 5.40 log10 copies/mL, P = 0.004). We identified 138 RTCs ranging from 2 to 14 patients and including overall 41% from the global population. Patients in RTCs were younger, more frequently born in France and more frequently MSM.ConclusionsSince 2007, the proportion of TDRAMs has been stable among French PHI patients. Non-B lineages are increasing and may be associated with more virulent CRF02_AG strains. The presence of large RTCs highlights the need for real-time cluster identification to trigger specific prevention action to achieve better control of the epidemic.

Published
2019

46. Emerging resistance mutations in PI-naive patients failing an atazanavir-based regimen (ANRS multicentre observational study)

Author

Lambert-Niclot, L, Grude, C, Chaix, L., Charpentier, L, Reigadas, C, Le Guillou-Guillemette, L, Rodallec, C, Maillard, Pascale, Dufayard, C, Mourez, C, Mirand, C, Guinard, L, Montes, S, Vallet, L, Marcelin, Marc, Descamps, L, Flandre, C, Delaugerre, L, Alloui, Chakib, Descamps, Diane, Charpentier, Charlotte, Visseaux, Benoit, Krivine, Anne, Bouviers-Alias, Ali, Pallier, Coralie, Soulié, Cathia, Wirden, Marc, Marcelin, Anne, Calvez, Vincent, Morand, Laurence, Lambert-Niclot, Sidonie, Fofana, Djeneba, Mahjoub, Nadia, Delaugerre, Constance, Chaix, Marie, Amiel, Corinne, Schneider, Veronique, Roussel, Catherine, Le Guillou-Guillemette, Hélène, Courdavault, Laurence, Reigadas, Sandrine, Recordon-Pinson, Patricia, Fleury, Hervé, Vallet, Sophie, Dina, Julia, Vabret, Astrid, Mirand, Audrey, Henquell, Cécile, Auvray, Christelle, de Rougemont, Alexis, Giraudon, Helene, Si-Mohammed, Ali, Mathez, Dominique, Signori-Schmuck, Anne, Morand, Patrice, Bocket, Laurence, Trabaud, Anne, Montes, Brigitte, Le Guen, Laura, Rodallec, Audrey, Ferré, Virginie, Jeulin, Hélène, SCHVOERER, Evelyne, Dufayard, Jacqueline, Allardet-Servent, Annick, carles, Marie, Guinard, Jérôme, Guigon, Aurélie, Giraudeau, Genevieve, Beby-Defaux, Agnès, Maillard, Anne, Plantier, Jean Christophe, Leoz, Marie, Mourez, Thomas, Bourlet, Thomas, Fafi-Kremer, Samira, Chiabrando, Julie, Raymond, Stéphanie, Izopet, Jacques, Barin, Francis, Marque-Juillet, Stéphanie, Yerly, Sabine, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Pontchaillou, Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Rouen, Normandie Université (NU), CHU Clermont-Ferrand, Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service de virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Mathématiques et Applications - ENS Paris (DMA), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Département d'Astrophysique, de physique des Particules, de physique Nucléaire et de l'Instrumentation Associée (DAPNIA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne (UB), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Victor Dupouy, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Laboratoire de Virologie Humaine et Moléculaire [Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de sérologie-virologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Raymond Poincaré [AP-HP], Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Département de virologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Service de Virologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Epidémiologie, Démographie et Sciences Sociales: santé reproductive, sexualité et infection à VIH (Inserm U569), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d'études démographiques (INED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Observatoire des Programmes Communautaires de Développement Rural (US ODR), Institut National de la Recherche Agronomique (INRA), Institut Pasteur de Nouvelle-Calédonie, Réseau International des Instituts Pasteur (RIIP), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Ecophysiologie Végétale, Agronomie et Nutritions (EVA), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Claude de Préval (ICP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université de Tours (UT), Centre Hospitalier de Versailles André Mignot (CHV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), École normale supérieure - Paris (ENS-PSL), Microbiologie Fondamentale et Pathogénicité (MFP), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Université Jean Monnet - Saint-Étienne (UJM), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université de Tours, Service de Virologie [CHU Pitié-Salpêtrière], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Lycée agricole La Touche, Hôpital Bichat - Claude Bernard, Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2, Memo-Flu-ARDS Study Group, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Tenon [APHP], Hôpital d'Argenteuil, Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital Raymond Poincaré [Garches], Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de virologie moléculaire et structurale, CHU Grenoble, Laboratoire de virologie [CHU Lille], Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national d'études démographiques (INED), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre national de référence du VIH INSERM U966, Centre Hospitalier de Versailles (CHV), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
0301 basic medicine, Microbiology (medical), Adult, Male, medicine.medical_specialty, 030106 microbiology, Atazanavir Sulfate, HIV Infections, Emtricitabine, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Abacavir, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Drug Resistance, Viral, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Treatment Failure, Tenofovir, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Pharmacology, business.industry, virus diseases, Lamivudine, HIV Protease Inhibitors, Middle Aged, Viral Load, Resistance mutation, Dideoxynucleosides, 3. Good health, Atazanavir, Regimen, Drug Combinations, Infectious Diseases, Mutation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Ritonavir, business, Viral load, medicine.drug
Abstract

Background Atazanavir is a PI widely used as a third agent in combination ART. We aimed to determine the prevalence and the patterns of resistance in PI-naive patients failing on an atazanavir-based regimen. Methods We analysed patients failing on an atazanavir-containing regimen used as a first line of PI therapy. We compared the sequences of reverse transcriptase and protease before the introduction of atazanavir and at failure [two consecutive viral loads (VLs) >50 copies/mL]. Resistance was defined according to the 2014 Agence Nationale de Recherche sur le SIDA et les Hepatites Virales (ANRS) algorithm. Results Among the 113 patients, atazanavir was used in the first regimen in 71 (62.8%) patients and in the first line of a PI-based regimen in 42 (37.2%). Atazanavir was boosted with ritonavir in 95 (84.1%) patients and combined with tenofovir/emtricitabine or lamivudine (n = 81) and abacavir/lamivudine or emtricitabine (n = 22). At failure, median VL was 3.05 log10 copies/mL and the median CD4+ T cell count was 436 cells/mm3. The median time on atazanavir was 21.2 months. At failure, viruses were considered resistant to atazanavir in four patients (3.5%) with the selection of the following major atazanavir-associated mutations: I50L (n = 1), I84V (n = 2) and N88S (n = 1). Other emergent PI mutations were L10V, G16E, K20I/R, L33F, M36I/L, M46I/L, G48V, F53L, I54L, D60E, I62V, A71T/V, V82I/T, L90M and I93L/M. Emergent NRTI substitutions were detected in 21 patients: M41L (n = 2), D67N (n = 3), K70R (n = 1), L74I/V (n = 3), M184V/I (n = 16), L210W (n = 1), T215Y/F (n = 3) and K219Q/E (n = 2). Conclusions Resistance to atazanavir is rare in patients failing the first line of an atazanavir-based regimen according to the ANRS. Emergent NRTI resistance-associated mutations were reported in 18% of patients.

Published
2018

47. CCR5 structural plasticity shapes HIV-1 phenotypic properties

Author

Colin, Philippe, Zhou, Zhicheng, Staropoli, Isabelle, Garcia-Perez, Javier, Gasser, Romain, Armani-Tourret, Marie, Benureau, Yann, Gonzalez, Nuria, Jin, Jun, Connell, Bridgette J., Raymond, Stéphanie, Delobel, Pierre, Izopet, Jacques, Lortat-Jacob, Hugues, Alcami, Jose, Arenzana-Seisdedos, Fernando, Brelot, Anne, Lagane, Bernard, Agence Nationale de Recherches sur le sida et les hépatites virales (Francia), Institut National de la Santé et de la Recherche Médicale (Francia), Instituto de Salud Carlos III, Pathogénie Virale - Viral Pathogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto de Salud Carlos III [Madrid] (ISC), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), This work was supported by Agence Nationale de Recherche sur le SIDA et les hépatites virales (ANRS) (http://www.anrs.fr/fr), Institut National de la Santé et de la Recherche Médicale (INSERM) (https://www.inserm.fr), Institut Pasteur (https://www.pasteur.fr), Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (Grant ANR-10-LABEX-62-IBEID) (https://research.pasteur.fr/fr/program_project/integrative-biology-of-emerging-infectious-diseases). This work used the platforms of the Grenoble Instruct Centre (ISBG, UMS 3518 CNRS-CEA-UJF-EMBL) (http://www.isbg.fr) with support from FRISBI (ANR-10-INSB-05-02) and GRAL (ANR-10-LABX-49-01) within the Grenoble Partnership for Structural Biology (PSB). JGP was supported by Spanish Ministry of Economy and Competitiveness-ISCIII-FIS No PI16CIII/00034. BJC was supported by a grant from Sidaction (https://www.sidaction.org) and 'la Fondation Pierre Bergé'. ZZ and RG were supported by a grant from ANRS. YB was supported by grants from ANRS and SIDACTION. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Pathogénie Virale, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
RNA viruses, viruses, HIV Infections, Signal transduction, HIV Envelope Protein gp120, Pathology and Laboratory Medicine, Physical Chemistry, Cell Fusion, White Blood Cells, Immunodeficiency Viruses, Animal Cells, Medicine and Health Sciences, Biology (General), Materials, T Cells, virus diseases, Chemistry, Phenotype, Medical Microbiology, Viral Pathogens, Viruses, Physical Sciences, Pathogens, Cellular Types, Dimerization, Coreceptors, Research Article, Protein Binding, Cell Binding, Cell Physiology, Receptors, CCR5, QH301-705.5, Immune Cells, Immunology, Materials Science, Research and Analysis Methods, Microbiology, Retroviruses, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, CCR5 coreceptor, Dimers, Molecular Biology Techniques, Microbial Pathogens, Molecular Biology, Blood Cells, Lentivirus, Organisms, Biology and Life Sciences, HIV, Cell Biology, RC581-607, Virus Internalization, Polymer Chemistry, Chemical Properties, Oligomers, HIV-1, Immunologic diseases. Allergy, Cloning
Abstract

CCR5 plays immune functions and is the coreceptor for R5 HIV-1 strains. It exists in diverse conformations and oligomerization states. We interrogated the significance of the CCR5 structural diversity on HIV-1 infection. We show that envelope glycoproteins (gp120s) from different HIV-1 strains exhibit divergent binding levels to CCR5 on cell lines and primary cells, but not to CD4 or the CD4i monoclonal antibody E51. This owed to differential binding of the gp120s to different CCR5 populations, which exist in varying quantities at the cell surface and are differentially expressed between different cell types. Some, but not all, of these populations are antigenically distinct conformations of the coreceptor. The different binding levels of gp120s also correspond to differences in their capacity to bind CCR5 dimers/oligomers. Mutating the CCR5 dimerization interface changed conformation of the CCR5 homodimers and modulated differentially the binding of distinct gp120s. Env-pseudotyped viruses also use particular CCR5 conformations for entry, which may differ between different viruses and represent a subset of those binding gp120s. In particular, even if gp120s can bind both CCR5 monomers and oligomers, impairment of CCR5 oligomerization improved viral entry, suggesting that HIV-1 prefers monomers for entry. From a functional standpoint, we illustrate that the nature of the CCR5 molecules to which gp120/HIV-1 binds shapes sensitivity to inhibition by CCR5 ligands and cellular tropism. Differences exist in the CCR5 populations between T-cells and macrophages, and this is associated with differential capacity to bind gp120s and to support viral entry. In macrophages, CCR5 structural plasticity is critical for entry of blood-derived R5 isolates, which, in contrast to prototypical M-tropic strains from brain tissues, cannot benefit from enhanced affinity for CD4. Collectively, our results support a role for CCR5 heterogeneity in diversifying the phenotypic properties of HIV-1 isolates and provide new clues for development of CCR5-targeting drugs., Author summary CCR5 regulates host immune responses against pathogens. It also serves as an anchor for R5-tropic strains of HIV-1 to infect immune cells, hence contributing to development of AIDS. CCR5 exists in different forms (e.g. conformations, oligomerization states), but the mechanisms that govern this diversity and its consequences on the physio-/pathophysio-logical functions of the receptor remain unclear. Because genetically diverse viral isolates populate HIV-1 infected individuals, we asked whether divergent viruses differ in the nature of the CCR5 molecules they use, and if so, whether this accounts for differences in their biological properties. Here we answered in the positive to both questions. We also identified CCR5 oligomerization as a key process regulating the receptor conformational diversity, the extent to which HIV-1 envelope glycoproteins bind to target cells and viral entry efficacy. From a functional standpoint, the nature/quantity of the receptor populations that are used by HIV-1 isolates regulates the type of cells they can infect and their ability to escape inhibition by CCR5 ligands. This study thus represents a step forward toward understanding of the mechanisms that regulate CCR5 diversity and its implications on the virus biological properties while opening new avenues for the development of drugs targeting CCR5.

Published
2018

49. Genotypic prediction of HIV-1 subtype D tropism

Author

Chaix Marie-Laure, Delobel Pierre, Raymond Stéphanie, Cazabat Michelle, Encinas Stéphanie, Bruel Patrick, Sandres-Sauné Karine, Marchou Bruno, Massip Patrice, and Izopet Jacques

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background HIV-1 subtype D infections have been associated with rapid disease progression and phenotypic assays have shown that CXCR4-using viruses are very prevalent. Recent studies indicate that the genotypic algorithms used routinely to assess HIV-1 tropism may lack accuracy for non-B subtypes. Little is known about the genotypic determinants of HIV-1 subtype D tropism. Results We determined the HIV-1 coreceptor usage for 32 patients infected with subtype D by both a recombinant virus phenotypic entry assay and V3-loop sequencing to determine the correlation between them. The sensitivity of the Geno2pheno10 genotypic algorithm was 75% and that of the combined 11/25 and net charge rule was 100% for predicting subtype D CXCR4 usage, but their specificities were poor (54% and 68%). We have identified subtype D determinants in the V3 region associated with CXCR4 use and built a new simple genotypic rule for optimizing the genotypic prediction of HIV-1 subtype D tropism. We validated this algorithm using an independent GenBank data set of 67 subtype D V3 sequences of viruses of known phenotype. The subtype D genotypic algorithm was 68% sensitive and 95% specific for predicting X4 viruses in this data set, approaching the performance of genotypic prediction of HIV-1 subtype B tropism. Conclusion The genotypic determinants of HIV-1 subtype D coreceptor usage are slightly different from those for subtype B viruses. Genotypic predictions based on a subtype D-specific algorithm appear to be preferable for characterizing coreceptor usage in epidemiological and pathophysiological studies.

Published
2011
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50. Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Author

Soulie, Cathia, Descamps, Diane, Grudé, Maxime, Schneider, Véronique, Trabaud, Mary-Anne, Morand-Joubert, Laurence, Delaugerre, Constance, Montes, Brigitte, Barin, Francis, Ferre, Virginie, Raymond, Stéphanie, Jeulin, Hélène, Alloui, Chakib, Yerly, Sabine, Pallier, Coralie, Reigadas, Sandrine, Signori-Schmuck, Anne, Guigon, Aurélie, Fafi-Kremer, Samira, Haïm-Boukobza, Stéphanie, Mirand, Audrey, Maillard, Anne, Vallet, Sophie, Roussel, Catherine, Assoumou, Lambert, Calvez, Vincent, Flandre, Philippe, Marcelin, Anne-Geneviève, 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, J.C., Trabaud, M.A., 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, A.G., Calvez, V., Lambert-Niclot, S., Soulié, C., Wirden, M., Morand-Joubert, L., Delaugerre, C., Chaix, M.L., Amiel, C., Schneider, V., Giraudeau, G., Brodard, V., Maillard, A., Plantier, J.C., Chaplain, C., Bourlet, T., Fafi-Kremer, S., Stoll-Keller, F., Schmitt, M.P., Barth, H., Yerly, S., Poggi, C., Izopet, J., Raymond, S., Barin, F., Chaillon, A., Marque-Juillet, S., Roque-Afonso, A.M., Haïm-Boukobza, S., Flandre, P., Grudé, M., Assoumou, L., Costagliola, D., Allegre, T., Schmit, J.L., Chennebault, J. M., Bouchaud, O., Magy-Bertrand, N., Delfraissy, J.F., Dupon, M., Morlat, P., Neau, D., Ansart, S., Jaffuel, S., Verdon, R., Jacomet, C., Lévy, Y., Dominguez, S., Chavanet, P., Piroth, L., Cabié, A., Leclercq, P., Ajana, F., Cheret, A., Weinbreck, P., Cotte, L., Poizot-Martin, I., Ravaud, I., Christian, B., Truchetet, F., Grandidier, M., Reynes, J., May, T., Goehringer, F., Raffi, F., Dellamonica, P., Prazuck, T., Hocqueloux, L., Yéni, P., Landman, R., Launay, O., Weiss, L., Viard, J.P., Katlama, C., Simon, A., Girard, P.M., Meynard, J.L., Molina, J.M., Pialoux, G., Hoen, B., Goeger-Sow, M.T., Lamaury, I., Beaucaire, G., Jaussaud, R., Rouger, C., Michelet, C., Borsa-Lebas, F., Caron, F., Khuong, M.A., Lucht, F., Rey, D., Calmy, A., Marchou, B., Gras, G., Greder-Belan, A., Vittecoq, D., and Teicher, E.

Subjects
virus diseases
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
2017

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