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Dive into the research topics where Bernard Masquelier is active.

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Featured researches published by Bernard Masquelier.


Lancet Infectious Diseases | 2011

Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study

Linda Wittkop; Huldrych F. Günthard; Frank de Wolf; David Dunn; Alessandro Cozzi-Lepri; Andrea De Luca; Claudia Kücherer; Niels Obel; Viktor von Wyl; Bernard Masquelier; Christoph Stephan; Carlo Torti; Andrea Antinori; Federico García; Ali Judd; Kholoud Porter; Rodolphe Thiébaut; Hannah Castro; Ard van Sighem; Céline Colin; Jesper Kjaer; Jens D. Lundgren; Roger Paredes; Anton Pozniak; Bonaventura Clotet; Andrew N. Phillips; Deenan Pillay; Geneviève Chêne

BACKGROUND The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration. METHODS HIV-infected patients of any age were included if they started cART (at least three antiretroviral drugs) for the first time after Jan 1, 1998, and were antiretroviral naive and had at least one sample for a genotypic test taken before the start of cART. We used the WHO drug resistance list and the Stanford algorithm to classify patients into three resistance categories: no TDR, at least one mutation and fully-active cART, or at least one mutation and resistant to at least one prescribed drug. Virological failure was defined as time to the first of two consecutive viral load measurements over 500 copies per mL after 6 months of therapy. FINDINGS Of 10,056 patients from 25 cohorts, 9102 (90·5%) had HIV without TDR, 475 (4·7%) had at least one mutation but received fully-active cART, and 479 (4·8%) had at least one mutation and resistance to at least one drug. Cumulative Kaplan-Meier estimates for virological failure at 12 months were 4·2% (95% CI 3·8-4·7) for patients in the no TDR group, 4·7% (2·9-7·5) for those in the TDR and fully-active cART group, and 15·1% (11·9-19·0) for those in the TDR and resistant group (log-rank p<0·0001). The hazard ratio for the difference in virological failure between patients with TDR and resistance to at least one drug and those without TDR was 3·13 (95% CI 2·33-4·20, p<0·0001). The hazard ratio for the difference between patients with TDR receiving fully-active cART and patients without TDR was 1·47 (95% CI 0·19-2·38, p=0·12). In stratified analysis, the hazard ratio for the risk of virological failure in patients with TDR who received fully-active cART that included a non-nucleoside reverse transcriptase inhibitor (NNRTI) compared with those without TDR was 2·0 (95% CI 0·9-4·7, p=0·093). INTERPRETATION These findings confirm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients. FUNDING European Communitys Seventh Framework Programme FP7/2007-2013 and Gilead.


JAMA | 2011

Low-Frequency HIV-1 Drug Resistance Mutations and Risk of NNRTI-Based Antiretroviral Treatment Failure A Systematic Review and Pooled Analysis

Jonathan Z. Li; Roger Paredes; Heather J. Ribaudo; Evguenia Svarovskaia; Karin J. Metzner; Michael J. Kozal; Katherine Huppler Hullsiek; Melanie Balduin; Martin R. Jakobsen; Anna Maria Geretti; Rodolphe Thiébaut; Lars Østergaard; Bernard Masquelier; Jeffrey A. Johnson; M.D. Miller; Daniel R. Kuritzkes

CONTEXT Presence of low-frequency, or minority, human immunodeficiency virus type 1 (HIV-1) drug resistance mutations may adversely affect response to antiretroviral treatment (ART), but evidence regarding the effects of such mutations on the effectiveness of first-line ART is conflicting. OBJECTIVE To evaluate the association of preexisting drug-resistant HIV-1 minority variants with risk of first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral virologic failure. DATA SOURCES Systematic review of published and unpublished studies in PubMed (1966 through December 2010), EMBASE (1974 through December 2010), conference abstracts, and article references. Authors of all studies were contacted for detailed laboratory, ART, and adherence data. STUDY SELECTION AND DATA ABSTRACTION Studies involving ART-naive participants initiating NNRTI-based regimens were included. Participants were included if all drugs in their ART regimen were fully active by standard HIV drug resistance testing. Cox proportional hazard models using pooled patient-level data were used to estimate the risk of virologic failure based on a Prentice weighted case-cohort analysis stratified by study. DATA SYNTHESIS Individual data from 10 studies and 985 participants were available for the primary analysis. Low-frequency drug resistance mutations were detected in 187 participants, including 117 of 808 patients in the cohort studies. Low-frequency HIV-1 drug resistance mutations were associated with an increased risk of virologic failure (hazard ratio (HR], 2.3 [95% confidence interval {CI}, 1.7-3.3]; P < .001) after controlling for medication adherence, race/ethnicity, baseline CD4 cell count, and plasma HIV-1 RNA levels. Increased risk of virologic failure was most strongly associated with minority variants resistant to NNRTIs (HR, 2.6 [95% CI, 1.9-3.5]; P < .001). Among participants from the cohort studies, 35% of those with detectable minority variants experienced virologic failure compared with 15% of those without minority variants. The presence of minority variants was associated with 2.5 to 3 times the risk of virologic failure at either 95% or greater or less than 95% overall medication adherence. A dose-dependent increased risk of virologic failure was found in participants with a higher proportion or quantity of drug-resistant variants. CONCLUSION In a pooled analysis, low-frequency HIV-1 drug resistance mutations, particularly involving NNRTI resistance, were significantly associated with a dose-dependent increased risk of virologic failure with first-line ART.


Lancet Infectious Diseases | 2011

European guidelines on the clinical management of HIV-1 tropism testing

Linos Vandekerckhove; Annemarie M. J. Wensing; Rolf Kaiser; F Brun-Vezinet; Bonaventura Clotet; A. De Luca; S. Dressler; F. García; Anna Maria Geretti; Thomas Klimkait; Klaus Korn; Bernard Masquelier; Carlo Federico Perno; Jonathan M. Schapiro; Vincent Soriano; Anders Sönnerborg; Anne-Mieke Vandamme; Chris Verhofstede; Hauke Walter; Maurizio Zazzi; Charles A. Boucher

Viral tropism is the ability of viruses to enter and infect specific host cells and is based on the ability of viruses to bind to receptors on those cells. Testing for HIV tropism is recommended before prescribing a chemokine receptor blocker. In most European countries, HIV tropism is identified with tropism phenotype testing. New data support genotype analysis of the HIV third hypervariable loop (V3) for the identification of tropism. The European Consensus Group on clinical management of tropism testing was established to make recommendations to clinicians and clinical virologists. The panel recommends HIV-tropism testing for the following groups: drug-naive patients in whom toxic effects are anticipated or for whom few treatment options are available; patients who have poor tolerability to or toxic effects from current treatment or who have CNS pathology; and patients for whom therapy has failed and a change in treatment is considered. In general, an enhanced sensitivity Trofile assay and V3 population genotyping are the recommended methods. Genotypic methods are anticipated to be used more frequently in the clinical setting because of their greater accessibility, lower cost, and faster turnaround time than other methods. For the interpretation of V3 loop genotyping, clinically validated systems should be used when possible. Laboratories doing HIV tropism tests should have adequate quality assurance measures. Similarly, close collaboration between HIV clinicians and virologists is needed to ensure adequate diagnostic and treatment decisions.


Journal of Acquired Immune Deficiency Syndromes | 2005

French national sentinel survey of antiretroviral drug resistance in patients with HIV-1 primary infection and in antiretroviral-naive chronically infected patients in 2001-2002.

Diane Descamps; Marie-Laure Chaix; André P; Brodard; Jacqueline Cottalorda; Christiane Deveau; Harzic M; Ingrand D; Jacques Izopet; Kohli E; Bernard Masquelier; Mouajjah S; Palmer P; Isabelle Pellegrin; Jean-Christophe Plantier; Poggi C; Rogez S; Annick Ruffault; Schneider; Signori-Schmück A; Catherine Tamalet; Marc Wirden; Christine Rouzioux; Françoise Brun-Vézinet; Laurence Meyer; Dominique Costagliola

Objective:To survey the frequency of genotypic antiretroviral resistance and the spread of non-B subtypes in patients with primary HIV-1 infection (2001-2002) and in treatment-naive chronically HIV-1-infected patients (2001). Methods:Plasma samples from 303 patients with acute HIV-1 infection (Primo study) and 363 treatment-naive patients with chronic HIV-1 infection (Odyssee study) were tested for genotypic resistance. Resistance mutations were identified from the International AIDS Society Resistance Testing-USA panel and resistant viruses were defined according to the French Agence Nationale de Recherches sur le SIDA (ANRS) resistance algorithm. Results:In the Primo study, 14% of the patients had viruses with resistance mutations and 12% of patients had viruses with mutations conferring resistance to least 1 antiretroviral drug. Thirty patients had viruses with mutations to at least 1 antiretroviral drug in a single pharmacologic class. Six patients were infected by viruses resistant to 2 or 3 classes of drugs. In the Odyssee study, the prevalence of reverse transcript (RT) associated and major protease inhibitor-associated mutations was 6.1% (95% CI: 3.6-8.6). Six patients had viruses resistant to at least 1 antiretroviral drug and 3 patients had viruses resistant to 2 classes of antiretroviral drugs. Twenty-four percent of acutely infected patients harbored non-B subtype strains (19% in 1999-2000) and 33.2% of chronically infected patients (10% in 1998; P < 0.0001). Conclusion:In France, the frequency of HIV-1 resistance in untreated patients was not significantly higher in 2001-2002 than in previous surveys while the prevalence of non-B subtypes is increasing.


Antimicrobial Agents and Chemotherapy | 2002

Human Immunodeficiency Virus Type 1 Genotypic and Pharmacokinetic Determinants of the Virological Response to Lopinavir-Ritonavir-Containing Therapy in Protease Inhibitor-Experienced Patients

Bernard Masquelier; Dominique Breilh; Didier Neau; Sylvie Lawson-Ayayi; Valérie Lavignolle; Jean-Marie Ragnaud; Michel Dupon; Philippe Morlat; F. Dabis; Hervé Fleury

ABSTRACT The response to regimens including lopinavir-ritonavir (LPV/r) in patients who have received multiple protease (PR) inhibitors (PI) can be analyzed in terms of human immunodeficiency virus type 1 (HIV-1) genotypic and pharmacokinetic (pK) determinants. We studied these factors and the evolution of HIV-1 resistance in response to LPV/r in a prospective study of patients receiving LPV/r under a temporary authorization in Bordeaux, France. HIV-1 PR and reverse transcriptase sequences were determined at baseline LPV/r for all the patients and at month 3 (M3) and M6 in the absence of response to treatment. pK measurements were determined at M1 and M3. Virological failure (VF) was defined as a plasma viral load ≥400 copies/ml at M3. A multivariate analysis of the predictors of VF, including clinical and biological characteristics and the treatment history of the patients, was performed. The PR gene sequence at M0, including individual mutations or a previously defined LPV mutation score (D. J. Kempf, J. D. Isaacson, M. S. King, S. C. Brun, Y. Xu, K. Real, B. M. Bernstein, A. J. Japour, E. Sun, and R. A. Rode, J. Virol. 75:7262-7269, 2001), and the individual exposure to LPV were also included covariates. Sixty-eight patients were enrolled. Thirty-four percent had a virological response at M3. An LPV mutation score of >5 mutations, the presence of the PR I54V mutation at baseline, a high number of previous PIs, prior therapy with ritonavir or indinavir, absence of coprescription of efavirenz, and a lower exposure to LPV or lower LPV trough concentrations were independently associated with VF on LPV/r. Additional PI resistance mutations, including primary mutation I50V, could be selected in patients failing on LPV/r. Genotypic and pK parameters should be used to optimize the virological response to LPV/r in PI-experienced patients and to avoid further viral evolution.


AIDS | 2008

Transmission of HIV-1 minority resistant variants and response to first-line antiretroviral therapy

Olivia Peuchant; Rodolphe Thiébaut; Sophie Capdepont; Valérie Lavignolle-Aurillac; Didier Neau; Philippe Morlat; François Dabis; Hervé Fleury; Bernard Masquelier

Background:The transmission of drug-resistant HIV-1 can impair the virological response to antiretroviral therapy. Minority-resistant variants have been detected in acute seroconverters. We investigated the clinical relevance of the detection of majority and minority-resistant variants in an observational study in antiretroviral therapy naive, recently infected patients. Methods:We included patients infected between 1996 and 2005, with a plasma sample obtained less than 18 months after seroconversion and prior to antiretroviral therapy initiation. Majority-resistant variants were determined by direct population sequencing. Minority-resistant variants were searched by allele-specific PCR for the mutations K103N and M184V in reverse transcriptase and L90M in protease. The association between resistance and viroimmunological response to antiretroviral therapy was estimated by using a piecewise linear mixed model. Results:Majority-resistant variants were detected in 23/172 (13.4%) patients. Patients with majority-resistant variants had a lower mean plasma viral load and higher mean CD4 cell count at baseline compared with those without resistance. The decrease in viral load between 1 and 6 months on antiretroviral therapy was significantly steeper in patients with sensitive viruses compared with those with majority-resistant variants (P = 0.029). Minority-resistant variants were detected in 21/73 (29%) patients with wild-type viruses at sequencing analysis. The presence of minority-resistant variants did not modify baseline viral load and CD4 cell count and did not affect the changes in viral load and CD4 cell count. Conclusion:The transmission of majority-resistant variants, but not minority-resistant variants, influenced the response to antiretroviral therapy in this prospective study. The detection of the transmission of minority-resistant variants warrants further clinical validation.


AIDS | 2009

Stable frequency of HIV-1 transmitted drug resistance in patients at the time of primary infection over 1996-2006 in France.

Marie-Laure Chaix; Diane Descamps; Marc Wirden; Laurence Bocket; Constance Delaugerre; Catherine Tamalet; Véronique Schneider; Jacques Izopet; Bernard Masquelier; Christine Rouzioux; Laurence Meyer; Dominique Costagliola

Background:Transmission of drug-resistant variants is influenced by several factors, including the HIV-1 RNA levels in HIV-1-infected patients. Our study describes the transmitted drug-resistant virus among 1446 French patients diagnosed at the time of primary infection and included from 1996 to 2006 along with the proportion of chronically infected treated patients in the French Hospital Database on HIV (FHDH). Methods:Genotypic resistance tests were performed at the time of primary infection. The proportion of patients with viral load <500 copies/ml among treated patients, enrolled in the FHDH, was calculated. Results:Over 1996–2006, the proportion of transmitted resistant viruses to at least one antiretroviral was estimated as 10.9%. When considering class resistance, there was an increase in transmission of nonnucleoside reverse transcriptase inhibitor-resistant virus from 0.6% in 1996–1998 to 4.4% in 1999 (P = 0.034), whereas no change was evidenced for either nucleoside/nucleotide reverse transcriptase inhibitor or protease inhibitor resistance. In the FHDH, the proportion of patients receiving combination antiretroviral therapy (cart) increased from 27.7% in 1996 to 81.4% in 2006 and the proportion of viral load <500 copies/ml in treated patients increased from 17.0% in 1996 to 85.3% in 2006. Phylogenetic analysis revealed that 25.5% of patients harboured HIV-1-non-B virus at the time of primary infection in 2005–2006 compared to 10% in 1996–1998. Conclusion:In this large study of patients at the time of primary infection, the frequency of acquired resistant virus was stable over time, over 5% for nucleoside/nucleotide reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor. One explanation for this stability may be the increasing number of treated patients in virological success.


Journal of Acquired Immune Deficiency Syndromes | 2005

Prevalence of transmitted HIV-1 drug resistance and the role of resistance algorithms - Data from seroconverters in the CASCADE collaboration from 1987 to 2003

Bernard Masquelier; Krishnan Bhaskaran; Deenan Pillay; Robert J. Gifford; Eric Balestre; Louise B. Jørgensen; Court Pedersen; Lia van der Hoek; Maria Prins; Claudia Balotta; Benedetta Longo; Claudia Kücherer; Gabriele Poggensee; Marta Ortiz; Carmen de Mendoza; John Gill; Hervé Fleury; Kholoud Porter

Objectives:To examine factors influencing the rate of transmitted drug resistance (TDR) among seroconverters, with particular emphasis on 3 widely used genotypic drug resistance algorithms. Methods:The study used data from CASCADE (Concerted Action on Seroconversion to AIDS and Death in Europe), a collaboration of seroconverter cohorts in Europe and Canada. Genotypic resistance data were derived within 18 months of the last seronegative test or date of laboratory evidence of acute infection and before the initiation of antiretroviral therapy. The Stanford algorithm was used to analyze each individuals nucleotide sequence. A multivariate logistic model was used to assess independent relationships between the presence of TDR and exposure category, sex, age at seroconversion, and year of seroconversion. The paper also describes 3 alternative definitions of resistance: the Stanford algorithm, the key resistance mutations defined by the International AIDS Society, and the Agence Nationale de Recherches sur le Sida (ANRS) algorithm. Results:Forty-five of 438 patients (10.3%) seroconverting between 1987 and 2003 were infected with a drug-resistant HIV-1 variant. Forty patients (9.1%) showed resistance mutations to only 1 class of antiretroviral drugs, 2 (0.5%) to 2 classes, and 3 (0.7%) to 3 classes of antiretroviral therapy. It was suggested that individuals seroconverting later in calendar time were more likely to have TDR (relative risk 3.89 and 95% CI: 0.84 to 18.02, and relative risk 4.69 and 95% CI: 1.03 to 21.31, for 1996-1999 and 2000-2003, respectively, compared with pre-1996; P trend = 0.08). This trend was apparent regardless of the definition of TDR used. The total estimated proportion of individuals with TDR varied between 10.3% and 15.5% according to which definition was used. Conclusions:Evidence was found for the rise of TDR over time. A specific definition of what constitutes TDR rather than a simple list of mutations is needed.


Antimicrobial Agents and Chemotherapy | 2010

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

Patricia Recordon-Pinson; Cathia Soulié; Philippe Flandre; Diane Descamps; Mouna Lazrek; Charlotte Charpentier; Brigitte Montes; Mary-Anne Trabaud; Jacqueline Cottalorda; Véronique Schneider; Laurence Morand-Joubert; Catherine Tamalet; Delphine Desbois; Muriel Macé; Virginie Ferré; Astrid Vabret; Annick Ruffault; Coralie Pallier; Jacques Izopet; Jacques Reynes; Anne-Geneviève Marcelin; Bernard Masquelier

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 <50 copies/ml was obtained in 68% of cases at month 6. In multivariate analysis, the prediction of the X4 genotype at baseline with the Geno2pheno10 algorithm including baseline viral load and CD4 nadir was independently associated with a worse VR at months 1 and 3. The baseline weighted genotypic sensitivity score was associated with VR at month 6. There were strong arguments in favor of using genotypic coreceptor use assays for determining which patients would respond to CCR5 antagonist.


Antimicrobial Agents and Chemotherapy | 2001

Genotypic and Phenotypic Resistance Patterns of Human Immunodeficiency Virus Type 1 Variants with Insertions or Deletions in the Reverse Transcriptase (RT): Multicenter Study of Patients Treated with RT Inhibitors

Bernard Masquelier; Esther Race; Catherine Tamalet; Diane Descamps; Jacques Izopet; Claudine Buffet-Janvresse; Annick Ruffault; Ali Si Mohammed; Jacqueline Cottalorda; Anne Schmuck; Vincent Calvez; Elisabeth Dam; Hervé Fleury; Françoise Brun-Vézinet

ABSTRACT Genomic rearrangements in the 5′ part of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) have been involved in multidrug resistance to nucleoside RT inhibitors (NRTI). We carried out a retrospective, multicenter study to investigate the prevalence, variability, and phenotypic consequences of such rearrangements. Data concerning the HIV-1 RT genotype and the biological and clinical characteristics of NRTI-treated patients were collected from 10 virology laboratories. Sensitivities of the different HIV-1 variants to RT inhibitors were analyzed in a single-cycle recombinant virus assay. Fifty-two of 2,152 (2.4%) RT sequences had a rearrangement in the 5′ part of the RT, with an extensive molecular variation. The number of codons inserted between positions 68 and 69 ranged from 1 (3 samples) or 2 (41 samples) to 5 and 11 in one case each. In four cases, codon 67 was deleted. High levels of phenotypic resistance to zidovudine (AZT), lamivudine (3TC), stavudine (d4T), abacavir (ABC), and didanosine (ddI) were found in 95, 92, 72, 62, and 15% of the 40 samples analyzed, respectively. Resistance to AZT, d4T, and ABC could be found in the absence of the T215Y/F mutations. Resistance to 3TC could develop in the absence of specific mutations. Low-level resistance to ddI was noticed in 40% of the patients. The deletions of codon 67 seemed to have little effect on NRTI sensitivity. Most of the rearrangements were shown to contribute to cross-resistance to NRTI. The results regarding susceptibility to ddI raise the question of the interpretation of the phenotypic data concerning this drug.

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Dominique Costagliola

French Institute of Health and Medical Research

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Catherine Tamalet

Centre national de la recherche scientifique

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