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1. 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

2. 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

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

Subjects
Male, Genome, Genotype, Rilpivirine, Drug Resistance, Antiretroviral Therapy, High-Throughput Nucleotide Sequencing, HIV Infections, Pharmacology and Pharmaceutical Sciences, Viral Load, Microbiology, Treatment Outcome, Medical Microbiology, Mutation, HIV-1, Humans, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group, Highly Active, Female, Viral
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. Concordance between Two Phenotypic Assays and Ultradeep Pyrosequencing for Determining HIV-1 Tropism

Author

Saliou, Adrien, Delobel, Pierre, Dubois, Martine, Nicot, Florence, Raymond, Stéphanie, Calvez, Vincent, Masquelier, Bernard, Izopet, Jacques, Renseigné, Non, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Service des Maladies Infectieuses et Tropicales, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Virology Laboratory, Hospital, Laboratoire de Virologie, Unité de Mathématiques Pures et Appliquées (UMPA-ENSL), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, VIROLOGIE, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Receptors, CXCR4, MESH: Sequence Analysis, DNA, Concordance, Viral quasispecies, MESH: Receptors, CCR5, Biology, MESH: Phenotype, Antiviral Agents, MESH: Receptors, CXCR4, MESH: HIV-1, 03 medical and health sciences, Genotype, Humans, Pharmacology (medical), Genotyping, Tropism, 030304 developmental biology, Pharmacology, Genetics, 0303 health sciences, MESH: Humans, MESH: Middle Aged, 030306 microbiology, virus diseases, MESH: Adult, Sequence Analysis, DNA, Middle Aged, Virology, 3. Good health, Viral Tropism, Phenotype, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, CCR5 Receptor Antagonists, HIV-1, Tissue tropism, Pyrosequencing, MESH: Viral Tropism, Trofile assay
Abstract

There have been few studies on the concordance between phenotypic assays for predicting human immunodeficiency virus type 1 (HIV-1) coreceptor usage. The sensitivity of ultradeep pyrosequencing combined with genotyping tools is similar to that of phenotypic assays for detecting minor CXCR4-using variants. We evaluated the agreement between two phenotypic assays, the Toulouse tropism test (TTT) and the Trofile assay, and ultradeep pyrosequencing for determining the tropism of HIV-1 quasispecies. The concordance between the TTT and Trofile assays was assessed for 181 samples successfully phenotyped by both assays. The TTT was 86% concordant with the standard Trofile assay and 91.7% with its enhanced-sensitivity version. The concordance between phenotypic characterization of HIV-1 tropism and ultradeep pyrosequencing genotypic prediction was further studied in selected samples. The HIV-1 tropism inferred from ultradeep pyrosequencing of 11 samples phenotyped as X4 and dualtropic and 12 phenotyped as R5-tropic agreed closely with the results of phenotyping. However, ultradeep pyrosequencing detected minor CXCR4-using variants in 3 of 12 samples phenotyped as R5-tropic. Ultradeep pyrosequencing also detected minor CXCR4-using variants that had been missed by direct sequencing in 6 of 9 samples phenotyped as X4-tropic but genotyped as R5-tropic by direct sequencing. Ultradeep pyrosequencing was 87% concordant with the Trofile and TTT phenotypic assays and was in the same range of sensitivity (0.4%) than these two phenotypic assays (0.3 to 0.5%) for detecting minor CXCR4-using variants. Ultradeep pyrosequencing provides a new way to improve the performance of genotypic prediction of HIV-1 tropism to match that of the phenotypic assays.

Published
2011

5. Evaluation of the Genotypic Prediction of HIV-1 Coreceptor Use versus a Phenotypic Assay and Correlation with the Virological Response to Maraviroc: the ANRS GenoTropism Study

Author

Recordon-Pinson, Patricia, Soulié, Cathia, Flandre, Philippe, Descamps, Diane, Lazrek, Mouna, Charpentier, Charlotte, Montes, Brigitte, Trabaud, Mary-Anne, Cottalorda, Jacqueline, Schneider, Véronique, Morand-Joubert, Laurence, Tamalet, Catherine, Desbois, Delphine, Macé, Muriel, Ferré, Virginie, Vabret, Astrid, Ruffault, Annick, Pallier, Coralie, Raymond, Stéphanie, Izopet, Jacques, Reynes, Jacques, Marcelin, Anne-Geneviève, Masquelier, Bernard, Renseigné, Non, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de microbiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Virology Laboratory, Hôpital Rothchild, Service de bactériologie-virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Virology, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Human and Molecular Virology, Georges Clémenceau Universitary Hospital, Unité de Rétrovirologie, Hôpital Pontchaillou, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Laboratoire de Virologie, Institut Fédératif de Biologie de Purpan, Variabilité génomique des virus, Université Bordeaux Segalen - Bordeaux 2-IFR66, Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Microbiologie Fondamentale et Pathogénicité (MFP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, Oncology, MESH: Sequence Analysis, DNA, Multivariate analysis, HIV Infections, HIV Envelope Protein gp120, MESH: Receptors, CCR5, Maraviroc, MESH: Genotype, MESH: HIV-1, Correlation, MESH: HIV Envelope Protein gp120, chemistry.chemical_compound, HIV Protease, HIV Fusion Inhibitors, Genotype, MESH: Receptors, HIV, Pharmacology (medical), MESH: Treatment Outcome, 0303 health sciences, MESH: Middle Aged, MESH: Tropism, MESH: HIV Infections, Middle Aged, MESH: Cyclohexanes, HIV Reverse Transcriptase, 3. Good health, Phenotype, Treatment Outcome, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, CCR5 Receptor Antagonists, Lentivirus, Female, Viral load, Adult, medicine.medical_specialty, Receptors, CCR5, MESH: HIV Reverse Transcriptase, Molecular Sequence Data, CCR5 receptor antagonist, Biology, MESH: Phenotype, Antiviral Agents, Sensitivity and Specificity, Tropism, MESH: HIV Protease, 03 medical and health sciences, Receptors, HIV, Cyclohexanes, Internal medicine, medicine, Humans, MESH: HIV Fusion Inhibitors, 030304 developmental biology, Pharmacology, MESH: Humans, MESH: Molecular Sequence Data, 030306 microbiology, MESH: Adult, Sequence Analysis, DNA, Triazoles, biology.organism_classification, Virology, MESH: Male, MESH: Sensitivity and Specificity, MESH: Triazoles, chemistry, Expanded access, HIV-1, MESH: Female
Abstract

Genotypic algorithms for prediction of HIV-1 coreceptor usage need to be evaluated in a clinical setting. We aimed at studying (i) the correlation of genotypic prediction of coreceptor use in comparison with a phenotypic assay and (ii) the relationship between genotypic prediction of coreceptor use at baseline and the virological response (VR) to a therapy including maraviroc (MVC). Antiretroviral-experienced patients were included in the MVC Expanded Access Program if they had an R5 screening result with Trofile (Monogram Biosciences). V3 loop sequences were determined at screening, and coreceptor use was predicted using 13 genotypic algorithms or combinations of algorithms. Genotypic predictions were compared to Trofile; dual or mixed (D/M) variants were considered as X4 variants. Both genotypic and phenotypic results were obtained for 189 patients at screening, with 54 isolates scored as X4 or D/M and 135 scored as R5 with Trofile. The highest sensitivity (59.3%) for detection of X4 was obtained with the Geno2pheno algorithm, with a false-positive rate set up at 10% (Geno2pheno10). In the 112 patients receiving MVC, a plasma viral RNA load of

Published
2010

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