Françoise Brun-Vézinet

Paris Diderot University, Lutetia Parisorum, Île-de-France, France

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Publications (207)1429.08 Total impact

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    ABSTRACT: In this study, we assessed phenotypic susceptibility to dolutegravir and raltegravir in a large variety of HIV-1 'non-B' subtypes (n = 72) issued from integrase inhibitor (INI)-naive clinical isolates. All samples were susceptible to both dolutegravir and raltegravir with median IC50 values of 1.22 nmol/l and 1.53 nmol/l, respectively; similar to what was observed for B subtype. Thus, despite the high prevalence of polymorphic substitutions in integrase in 'non-B' clinical isolates, phenotypic susceptibility to dolutegravir remained unchanged.
    AIDS (London, England) 08/2013; · 4.91 Impact Factor
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    ABSTRACT: Here we summarize the discussions and conclusions from an expert workshop held in October 2012 to consider the implications of HIV drug resistance in the context of scale-up of access to antiretroviral therapy and prophylaxis in resource-limited settings. Topics considered during the workshop included the implications of drug resistance for the selection of first-line regimens and sequencing of treatments, optimal surveillance strategies and prevention of mother-to-child transmission.
    Antiviral therapy 06/2013; · 3.07 Impact Factor
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    ABSTRACT: Recent data from studies on treatment as prevention (TasP) and preexposure prophylaxis (PrEP) show that antiretroviral drugs can be used in prevention, as well as in treatment. The movement from first-generation antiretroviral therapy (ART) coformulations based on thymidine analogues to second-generation ART coformulations based on tenofovir may coincide with future prevention strategies that also use tenofovir/emtricitabine, raising concerns regarding drug resistance. In published studies, failure of prophylaxis was associated with poor adherence and low plasma drug levels. Although rates of drug resistance in cases of failed prevention was low, regular human immunodeficiency virus (HIV) testing was undertaken in these clinical trials. Although legitimate concerns exist about ART adherence and drug resistance associated with PrEP and TasP in real-world settings, efforts to curb the continuing HIV epidemic through use of these novel prevention strategies should move forward because the development and approval of newer drugs reserved for prevention might take many more years. Efforts must be made to monitor ART adherence and to intervene through counseling and other means in order to optimize adherence and retention in care, whenever necessary. Finally, further research involving the generalized epidemic is needed to determine when suboptimal drug use may occur and when regular testing and monitoring of the long-term consequences of ART use may not be routine.
    The Journal of Infectious Diseases 06/2013; 207 Suppl 2:S101-6. · 5.85 Impact Factor
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    ABSTRACT: Considering HIV-2 phenotypic data; experience from HIV-1 and from the follow-up of HIV-2-infected patients, a panel of European experts voted on a rule set for interpretation of mutations in HIV-2 protease, reverse transcriptase and integrase and an automated tool for HIV-2 drug resistance analyses freely available on the internet (http://www.hiv-grade.de).
    Clinical Infectious Diseases 02/2013; · 9.37 Impact Factor
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    ABSTRACT: The aim of our study was to assess a possible association between plasma inflammatory biomarkers (CRP, IL-6, soluble CD14) and the extent of fibrosis or cirrhosis using a FibroScan® in HIV/HCV co-infected patients. This cross-sectional study assessed 60 HIV/HCV co-infected patients who had paired plasma samples and FibroScan® values available. All included patients were controlled for HIV infection (HIV-1 RNA <50 copies/mL) and had detectable HCV RNA levels. Levels of three biomarkers were measured in all samples using commercial ELISA kits. Multivariate logistic regression models identified factors associated with the METAVIR stages of fibrosis (F0-F2 vs. F3-F4). In univariate logistic regression analyses, in addition to sCD14 (odds ratio [OR] = 3.23, 95% confidence interval [95%CI] = 1.30-7.97, P = 0.01), aspartate aminotransferase (AST), alanine aminotransferase, platelet counts, and CD4 cell counts were associated with the stage of liver fibrosis and, thus, were introduced into the model. However, only AST (OR = 1.06, 95%CI = 1.02-1.10, P = 0.0009) was independently associated with F3-F4 stage liver fibrosis. In our study of HIV/HCV co-infected patients, sCD14 plasma level, a biomarker of monocyte activation, was not independently associated with the F3-F4 stage of liver fibrosis. We hypothesize that the higher levels of inflammation markers observed in HIV/HCV co-infected patients, compared to HCV mono-infected patients, prevent this association being observed within this population.
    PLoS ONE 01/2013; 8(3):e59205. · 3.73 Impact Factor
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    ABSTRACT: To describe the prevalence of the L76V protease inhibitors resistance-associated mutation (PI-RAM) in relation with patients' characteristics and protease genotypic background in HIV-1 B- and "non-B"-infected patients. Frequency of the L76V mutation between 1998 and 2010 was surveyed in the laboratory database of 3 clinical centers. Major PI-RAMs were identified according to the IAS-USA list. Fisher's and Wilcoxon tests were used to compare variables. Among the overall 29,643 sequences analyzed, the prevalence of L76V was 1.50%, while was 5.42% in PI-resistant viruses. Since 2008 the prevalence of L76V was higher in "non-B"-infected than in B-infected patients each year. Median time since diagnosis of HIV-1 infection and median time under antiretroviral-based regimen were both shorter in "non-B"- than in B-infected patients (8 vs 11 years, P<0.0001; and 7 vs 8 years, P = 0.004). In addition, "non-B"-infected patients had been pre-exposed to a lower number of PI (2 vs 3, P = 0.016). The L76V was also associated with a lower number of major PI-RAMs in "non-B" vs B samples (3 vs 4, P = 0.0001), and thus it was more frequent found as single major PI-RAM in "non-B" vs B subtype (10% vs 2%, P = 0.014). We showed an impact of viral subtype on the selection of the L76V major PI-RAM with a higher prevalence in "non-B" subtypes observed since 2008. In addition, in "non-B"-infected patients this mutation appeared more rapidly and was associated with less PI-RAM.
    PLoS ONE 01/2013; 8(1):e54381. · 3.73 Impact Factor
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    ABSTRACT: OBJECTIVE: In the ANRS 139 TRIO trial, the use of 3 new active drugs (raltegravir, etravirine, and darunavir/ritonavir), resulted in a potent and sustained inhibition of viral replication in multidrug-resistant treatment-experienced patients. The aim of this virological sub-study of the ANRS 139 TRIO trial was to assess: (i) the evolution of HIV-1 DNA over the first year; and (ii) the association between baseline HIV-1 DNA and virological outcome. METHODS: Among the 103 HIV-1-infected patients included in the ANRS-139 TRIO trial, HIV-1 DNA specimens were available for 92, 84, 88, and 83 patients at Week (W)0, W12, W24, and W48, respectively. Quantification of total HIV-1 DNA was performed by using the commercial kit "Generic HIV DNA Cell" (Biocentric, Bandol, France). RESULTS: Baseline median HIV-1 DNA of patients displaying virological success (n = 61), viral blip (n = 20), and virological failure (n = 11) were 2.34 log(10) copies/10(6) PBMC (IQR = 2.15-2.66), 2.42 (IQR = 2.12-2.48), and 2.68 (IQR = 2.46-2.83), respectively. Although not statistically significant, patients exhibiting virological success or viral blip had a tendency to display lower baseline HIV-1 DNA than patients experiencing virological failure (P = 0.06). Median decrease of HIV-1 DNA between baseline and W48 was -0.13 log(10) copies/10(6) PBMC (IQR = -0.34 to +0.10), mainly explained by the evolution from W0 to W4. No more changes were observed in the W4-W48 period. CONCLUSIONS: In highly-experienced multidrug-resistant patients, HIV-1 DNA slightly decreased during the first month and then remained stable during the first year of highly potent antiretroviral regimen. In this population, baseline HIV-1 DNA might help to better predict the virological response and to tailor clinical therapeutic management as more aggressive therapeutic choices in patients with higher baseline HIV-1 DNA.
    PLoS ONE 01/2013; 8(1):e53621. · 3.73 Impact Factor
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    ABSTRACT: The HIV-1 coreceptor usage may play a critical role in AIDS pathogenesis and the X4-using viruses are considered to be more pathogenic than the R5-tropic viruses. These observations may influence the therapeutic decisions by asking for an earlier antiretroviral (ARV) treatment for the patients infected by the X4-tropic viruses compared with those infected by the R5-tropic viruses. The natural evolution of CD4+ cell count for 109 non-treated patients infected by the R5- or X4-tropic HIV-1 viruses with CD4+ >350 and >500 cells/mm(3) at time of diagnosis was compared until the initiation of an ARV regimen. The coreceptor usage was determined from the V3 env region sequence by Geno2Pheno (false positive rate 10%). A mixed linear regression model to analyse the CD4+ data with tropism as fixed effect in the model was used. Overall, 93 (85.3%) and 16 (14.7%) were infected by R5- and X4-tropic viruses, respectively. The median age, baseline CD4+ cell count, and viral load were 34 years (IQR: 30-42), 523 cells/mm(3) (IQR: 420-604), and 4.5 log(10)  copies/ml (IQR: 3.9-5.0), respectively. There was no statistical difference in time to progression between the patients harboring R5- or X4-tropic viruses. The same results were observed for the sub-group of patients with CD4+ cell count >500 cells/mm(3) . The virus tropism has no impact on the CD4+ cell count evolution in these HIV-1 patients diagnosed with CD4+ >350 or >500 cells/mm(3) suggesting that the tropism determination at time of diagnosis does not seem to be a useful tool to predict the clinical progression. J. Med. Virol. 84:1853-1856, 2012. © 2012 Wiley Periodicals, Inc.
    Journal of Medical Virology 12/2012; 84(12):1853-6. · 2.37 Impact Factor
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    ABSTRACT: In this study assessing HIV-2 tropism among 43 paired plasma/PBMC specimens, the concordance between proviral DNA and plasma RNA genotypic tropism prediction was 74%. All the discordances were attributable to the prediction of R5 in RNA and X4/Dual-Mixed in DNA. HIV-2 genotypic tropism test based on proviral DNA is a suitable tool for tropism determination in HIV-2-infected patients with low or undetectable viral load.
    AIDS (London, England) 10/2012; · 4.91 Impact Factor
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    ABSTRACT: OBJECTIVE:: This study investigated the impact on virological outcome of the gag cleavage sites (CS) and the protease-coding region (PR) mutations in protease inhibitor (PI)-naïve and PI-experienced patients infected with HIV-2 receiving lopinavir-containing regimen. METHODS:: Baseline gag and PR were sequenced in 46 HIV-2 group-A-infected patients receiving lopinavir. Virological response (VR) was defined as plasma viral load (VL) <100 copies/mL at month 3. Associations between VR and frequencies of mutations in gag (MA/CA, CA/p2, p2/NC, NC/p1, p1/p6) and gag-pol (NC/p6) CS and PR, with respect to the HIV-2ROD strain, were tested using Fisher's exact test. RESULTS:: VR occurred in 14/17 (82%) PI-naïve and 17/29 (59%) PI-experienced patients. Virological failure (VF) was associated with higher baseline VL (median: 6 765 vs. 1 098 copies/mL, P = 0.02). More PR mutations were observed in PI-experienced compared to PI-naïve patients (median: 8 vs. 5, P = 0.003). In PI-naïve patients, T435A (NC/p6), V447 M (p1/p6), and Y14H (PR) were associated with VF (P = 0.011, P = 0.033, P = 0.022, respectively). T435A and V447 M were associated with Y14H (P = 0.018, P = 0.039, respectively). In PI-experienced patients, D427E (NC/p1) was associated with VR (P = 0.014). A430 V (NC/p1) and I82F (PR) were associated with VF (P = 0.046, P = 0.050, respectively). Mutations at position 430 were associated with a higher number of mutations in PR (median: 10 vs. 7, P = 0.008). CONCLUSIONS:: We have demonstrated, for the first time, an association between gag, gag-pol CS and PR mutations, with distinct profiles between PI-naïve and PI-experienced patients. These mutations might impact the virological outcome of HIV-2-infected patients receiving lopinavir-containing regimen.
    AIDS (London, England) 09/2012; · 4.91 Impact Factor
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    ABSTRACT: Background. Human immunodeficiency virus type 2 (HIV-2) infection is characterized by a slower progression than HIV type 1. It is not known whether markers of inflammation such as high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), and soluble CD14 (sCD14) may predict disease progression among HIV-2 patients. Methods. We performed longitudinal retrospective analysis using 384 samples from 71 patients included in the HIV-2 French cohort ANRS CO5 and followed for a median of 8 years. Baseline was the time of the first available measurement. Disease progression was defined by the occurrence of death, Centers for Disease Control and Prevention B/C stage HIV-related event, drop in CD4 <350 cells/µL, and HIV-2 RNA detection. Cox regression models and mixed models were used for statistical analyses. Results. At baseline, 75% of patients were asymptomatic, 34% were treated; 30% had detectable HIV-2 RNA load, and median CD4 cell count was 415/µL. The 3 biomarkers were positively related to each other. In adjusted analyses, sCD14 was the main factor explaining variation of hsCRP and IL-6 (P < .001). Lower CD4, older age, and advanced clinical stage were associated with higher sCD14. The biomarkers were correlated with HIV-2 RNA in unadjusted analyses only. Patients with baseline levels above either the median values (hsCRP = 1.38 mg/L; IL-6 = 1.97 pg/mL) or the highest quartile (sCD14 = 1.74 µg/mL) had a higher risk of disease progression (all P < .003). After adjustment for CD4 count, only sCD14 remained significantly associated with disease progression (hazard ratio, 3.59; P = .004). Conclusions. In this cohort of HIV-2-infected patients, sCD14 represents a better predictive biomarker of disease progression than hsCRP or IL-6, independent of CD4.
    Clinical Infectious Diseases 08/2012; 55(10):1417-1425. · 9.37 Impact Factor
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    ABSTRACT: The aim of our study was to identify factors associated with persistent low-level viraemia (LLV) in HIV-infected patients under suppressive antiretroviral therapy and to assess the virological outcome of these patients. LLV was defined as at least two HIV-1 RNA values between 20 and 50 copies/mL during 1 year of follow-up. We compared patients with all values <20 copies/mL (LLV-) and patients with LLV (LLV+). The 'blip ratio' was defined as (number of HIV-1 RNA values >50 copies/mL)/(number of HIV-1 RNA determinations) before study inclusion. Among the 656 patients included, 5.8% were in group LLV+. CDC stage B/C at study inclusion and a higher blip ratio before the study period were the only factors independently associated with LLV. During the 1 year follow-up, the proportion of patients experiencing virological failure was not different between the LLV- and LLV+ groups, and 40% of patients shifted from LLV+ to LLV- status. LLV was infrequent in our series and the follow-up did not evidence a higher rate of virological failure than in fully suppressed patients. LLV seems to be a transient phenomenon that might be driven by residual ongoing viral replication and/or viral release and/or accuracy of viral load assay at lower values.
    Journal of Antimicrobial Chemotherapy 05/2012; 67(9):2231-5. · 5.34 Impact Factor
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    ABSTRACT: BMS-626529 is a member of the new drug class of HIV-1 attachment inhibitors currently in development. Mutations selected during in vitro experiments with BMS-626529 are located in the gp120 region: L116P, A204D, M426L, M434I-V506M and M475I. A differential antiviral activity of BMS-626529 was observed depending of the viral subtype. The aim of our study was to assess the prevalence of subtype-related polymorphisms previously described as being associated with in vitro resistance to BMS-626529 in patients infected with different HIV-1 'non-B' subtypes. The prevalence of substitutions in gp120 was assessed in 85 HIV-infected patients (not previously treated with attachment inhibitors and infected with HIV-1 'non-B' subtypes) by performing direct sequencing of the gp120 region. The most prevalent HIV-1 subtype was CRF02_AG (n = 46, 54%). The M426L substitution was found in virus from 10 patients (11.8%), mainly in subtypes D and CRF02_AG. The M434I substitution was found in virus from 11 patients (12.9%), mainly in subtypes CRF02_AG and CRF06_cpx. None of the CRF02_AG viruses harboured both M426L and M434I substitutions. In our series, the M426L substitution in the gp120 region was detected in 46% and 7% of subtype D and CRF02_AG samples, respectively, and might affect the activity of BMS-626529 against these specific subtypes. Further studies are needed to better describe associations between HIV-1 'non-B'-subtype-related polymorphism profiles and the level of phenotypic resistance to attachment inhibitor BMS-626529.
    Journal of Antimicrobial Chemotherapy 03/2012; 67(6):1459-61. · 5.34 Impact Factor
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    ABSTRACT: Various items are complicating the treatment of HIV-2 infected patients. Compared to HIV-1 there is much less treatment experience, no evidence from randomized control trials, a reduced number of effective drugs and no broadly available test for viral load monitoring. In case of treatment failure there is only limited guidance and presently no easy accessible tool for nucleic acid sequence interpretation available. To solve this problem, we initiated an expert workshop to address some of these problems. A panel of experts from four different European countries voted on a rule set for interpretation of mutations in the HIV-2 protease, reverse transcriptase and integrase. Rules were proposed by each member and were then modified during discussion by considering data gained from HIV-1 and accumulated experience of the follow up of HIV-2-infected patients. Based on the HIV-GRADE internet-tool an online tool was developed to make the rule set easily accessible and usable. Rules were laid down for the interpretation of HIV-2 drug resistance to NRTIs, PIs and INIs (integrase inhibitors). Due to natural resistance of HIV-2, usage of NNRTIs and T-20 was not recommended as part of an antiretroviral regimen for HIV-2. These rules were then translated in a machine interpretable format (algorithm specification interface, ASI) and the HIV-GRADE tool was extended for usage of HIV-2 sequences. Further consensus sequences were generated from the reference sequence data set provided by Los Alamos National Laboratories. In contrast to HIV-1, mutations were compared to a group specific consensus sequence (Group A or Group B) and not to a consensus sequence from the most predominant HIV-2 Group A. This change was necessary due to significant differences between the various HIV-2 strains. We developed a rule set and an automated tool for HIV-2 drug resistance analyses. This tool and the rules will be freely available on the internet. Access to the pre-publication versions can be granted by each of the group members. To keep the algorithm rules up-to-date it will be actualized on a yearly basis.
    Journal of the International AIDS Society 01/2012; 15(6):18180. · 3.94 Impact Factor
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    ABSTRACT: In October 2009 the French National Authority for Health recommended that HIV testing be proposed at least once to all persons aged 15 to 70 years in all healthcare settings. We examined whether routine HIV screening with a rapid test in emergency departments (EDs) was feasible without dedicated staff, and whether newly diagnosed persons could be linked to care. This one-year study started in December 2009 in 6 EDs in the Paris area, using the INSTI™ test. Eligible individuals were persons 18 to 70 years old who did not present for a vital emergency, for blood or sexual HIV exposure, or for HIV screening. Written informed consent was required. Among 183 957 eligible persons, 11 401 were offered HIV testing (6.2%), of whom 7936 accepted (69.6%) and 7215 (90.9%) were tested (overall screening rate 3.9%); 1857 non eligible persons were also tested. Fifty-five new diagnoses of HIV infection were confirmed by Western blot (0.61% (95% CI 0.46-0.79). There was one false-positive rapid test result. Among the newly diagnosed persons, 48 (87%) were linked to care, of whom 36 were not lost to follow-up at month 6 (75%); median CD4 cell count was 241/mm(3) (IQR: 52-423/mm(3)). Screening rates were similar to those reported in opt-in studies with no dedicated staff. The rate of new diagnoses was similar to that observed in free anonymous test centres in the Paris area, and well above the prevalence (0.1%) at which testing has been shown to be cost-effective.
    PLoS ONE 01/2012; 7(10):e46437. · 3.73 Impact Factor
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    ABSTRACT: The use of CCR5 inhibitors requires a tool to predict human immunodeficiency virus type 2 (HIV-2) tropism, as established in HIV-1. The aim of our study was to identify genotypic determinants of HIV-2 tropism located in the gp105 V3 loop. HIV-2 tropism phenotypic assays were performed on 53 HIV-2 clinical isolates using GFP expressing human osteosarcoma T4 [GHOST(3)] cell lines expressing CD4 and CCR5 or CXCR4 coreceptors. The gp105 V3 loop was sequenced and analyzed. Thirty-four HIV-2 isolates were classified as R5, 7 as X4, and 12 as X4/R5 (dual). Substitution at residue 18 was always associated with a dual/X4 tropism (P < .00001). The following determinants were associated with dual/X4 tropism: a global net charge of more than +6 (P < .00001), V19K/R mutation (P < .00001), S22A/F/Y mutation (P < .002), Q23R mutation (P < .00001), and insertions at residue 24 (P < .00001), I25L/Y (P < .0004), R28K (P < .0004), and R30K (P < .014). These mutations were not found in R5 isolates, except R28K and R30K, which were detected in 4 and 5 R5 isolates, respectively. The 4 major genotypic determinants of dual/X4 tropism were mutation at residue 18, V19 K/R mutation, insertions at residue 24, and V3 global net charge. We established a strong association between HIV-2 phenotypic tropism and V3-loop sequences, allowing for the prediction of R5- and/or X4-tropic viruses in HIV-2 infection.
    The Journal of Infectious Diseases 12/2011; 205(1):111-20. · 5.85 Impact Factor
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    ABSTRACT: HIV-2 is naturally resistant to nonnucleoside reverse transcriptase inhibitors, to a fusion inhibitor, and to some of the protease inhibitors. Maraviroc is the first drug of the new anti-CCR5 drug class and is effective only on CCR5-tropic (R5) HIV-1. No previous studies concerning HIV-2 susceptibility to maraviroc have been reported yet. We developed a phenotypic maraviroc susceptibility test using a peripheral blood mononuclear cell (PBMC) model. We analyzed the maraviroc susceptibility of 13 R5 HIV-2, 2 X4R5 (dual) HIV-2, and 2 CXCR4-tropic (X4) HIV-2 clinical isolates. We also tested, with the same protocol, 1 X4 HIV-1 and 4 R5 HIV-1 clinical isolates. For the R5 HIV-2 clinical isolates, the 50% effective concentration (EC(50)) for maraviroc was 0.80 nM (interquartile range [IQR], 0.48 to 1.39 nM), similar to that observed for the R5 HIV-1 isolates. The median maximum percentage of inhibition in the R5 HIV-2 isolates was 93% (IQR, 84 to 98%), similar to that observed in the R5 HIV-1 isolates. As expected, both X4 HIV-1 and HIV-2 were highly resistant to maraviroc. Our study showed for the first time that maraviroc is active in vitro against R5 HIV-2. The new tools we developed will allow identification of HIV-2-infected patients eligible for CCR5 inhibitor use and management of virological failure when receiving a maraviroc-based regimen.
    Antimicrobial Agents and Chemotherapy 11/2011; 56(1):137-9. · 4.57 Impact Factor
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    ABSTRACT: Most of the previous studies that explored the molecular basis of raltegravir resistance were conducted studying the HIV-1 B subtype. It has been shown that the CRF02_AG subtype in relation to its natural integrase (IN) sequence could develop different genetic pathways associated with raltegravir resistance. The aim of this study was to explore resistance pathways preferably used by CRF02_AG viruses compared with subtype B. Twenty-five HIV-1 CRF02_AG-infected patients failing a raltegravir-containing regimen were studied. IN gene sequences were examined for the presence of previously described IN inhibitor (raltegravir, elvitegravir, dolutegravir and MK-2048) resistance mutations at 20 amino acid positions. Among the 25 studied patients, 7 showed viruses harbouring major raltegravir resistance mutations mainly associated with the 155 genetic pathways and 18 showed viruses harbouring none of them; however, for 1 patient, we found a 118R mutation, associated with MK-2048 in vitro resistance, in a 74M background. For this patient, the phenotypic analysis showed that addition of only the G118R mutation conferred a high level of resistance to raltegravir (fold change = 25.5) and elvitegravir (fold change = 9.2). This study confirmed that mutation pathways for raltegravir resistance could be different between the two subtypes CRF02_AG and B with a preferential use of the 155 mutation in non-B subtypes. A new genetic pathway associated with raltegravir resistance, including the 118R mutation, has also been identified. This new genetic pathway, never described in subtype B, should be further evaluated for phenotypic susceptibility to dolutegravir and MK-2048.
    Journal of Antimicrobial Chemotherapy 09/2011; 66(12):2827-30. · 5.34 Impact Factor
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    ABSTRACT: Recently, we have reported the role of baseline gag cleavage site mutations on the virological outcome of a dual-boosted protease inhibitor regimen in antiretroviral-naive patients (2IP-ANRS 127 trial). The objective of this substudy was to characterize, in patients experiencing virological failure, from the 2IP-ANRS 127 trial, the viral quasispecies present at baseline and at virological failure in gag cleavage site, in gag-pol frameshift and in protease-coding region. In four patients, we analysed by clonal analysis the viral population in gag cleavage site (p17/p24, p24/p2, p2/p7, p7/p1, p1/p6(gag)), in p6(gag), in gag-pol frameshift [p1/transframe protein (TFP)/p6(pol)] and in protease-coding region. Clonal analysis of protease-coding region failed to detect major as well as minor protease inhibitor resistance-associated mutations in all four patients. In one patient, a I15V-mutated variant increased from 13 to 100% between baseline and week 24. Clonal analysis of gag and gag-pol cleavage site showed an increase in specific viral populations in p2/p7 cleavage site between baseline and virological failure in three patients. Among them, we described in one patient, that the predominant population at virological failure harboured in p2/p7 and TFP/p6(pol)-specific genotypic profiles associated with duplication of the P(T)APP motif in p6(gag) and the I15V protease mutation on the same individual molecular clones. We highlighted the emergence of minority viral populations in the p2/p7 cleavage site between baseline and virological failure. In addition, we showed the association of a specific protease mutation with gag and gag-pol cleavage site substitutions, suggesting their possible role in virological outcome.
    AIDS (London, England) 09/2011; 25(17):2143-8. · 4.91 Impact Factor
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    ABSTRACT: Accurate HIV-2 plasma viral load quantification is crucial for adequate HIV-2 patient management and for the proper conduct of clinical trials and international cohort collaborations. This study compared the homogeneity of HIV-2 RNA quantification when using HIV-2 assays from ACHI(E)V(2E) study sites and either in-house PCR calibration standards or common viral load standards supplied to all collaborators. Each of the 12 participating laboratories quantified blinded HIV-2 samples, using its own HIV-2 viral load assay and standard as well as centrally validated and distributed common HIV-2 group A and B standards (http://www.hiv.lanl.gov/content/sequence/HelpDocs/subtypes-more.html). Aliquots of HIV-2 group A and B strains, each at 2 theoretical concentrations (2.7 and 3.7 log(10) copies/ml), were tested. Intralaboratory, interlaboratory, and overall variances of quantification results obtained with both standards were compared using F tests. For HIV-2 group A quantifications, overall and interlaboratory and/or intralaboratory variances were significantly lower when using the common standard than when using in-house standards at the concentration levels of 2.7 log(10) copies/ml and 3.7 log(10) copies/ml, respectively. For HIV-2 group B, a high heterogeneity was observed and the variances did not differ according to the type of standard used. In this international collaboration, the use of a common standard improved the homogeneity of HIV-2 group A RNA quantification only. The diversity of HIV-2 group B, particularly in PCR primer-binding regions, may explain the heterogeneity in quantification of this strain. Development of a validated HIV-2 viral load assay that accurately quantifies distinct circulating strains is needed.
    Journal of clinical microbiology 08/2011; 49(10):3491-7. · 4.16 Impact Factor

Publication Stats

5k Citations
1,429.08 Total Impact Points

Institutions

  • 2009–2013
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 1985–2013
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      • Service des Maladies Infectieuses et Tropicales
      Lutetia Parisorum, Île-de-France, France
  • 2003–2012
    • French Institute of Health and Medical Research
      • Epidemiology and Biostatistics Center
      Paris, Ile-de-France, France
  • 2009–2011
    • Université Victor Segalen Bordeaux 2
      Burdeos, Aquitaine, France
  • 2003–2011
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2010
    • Polytech Paris-UPMC
      Lutetia Parisorum, Île-de-France, France
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France
    • Pasteur Center of Cameroon
      Jaúnde, Centre Region, Cameroon
  • 2009–2010
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States
  • 2005–2008
    • Centre Hospitalier Universitaire Rouen
      Rouen, Upper Normandy, France
    • University of Bordeaux
      Burdeos, Aquitaine, France
  • 2003–2008
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2002–2007
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • ANRS - Agence Nationale de Recherche sur le Sida et les hépatites virales
      Lutetia Parisorum, Île-de-France, France
  • 2004
    • Universitatea de Medicina si Farmacie Grigore T. Popa Iasi
      • School of Medicine
      Iaşi, Judetul Iasi, Romania
  • 2002–2004
    • Centre Hospitalier Universitaire de Bordeaux
      Burdeos, Aquitaine, France
  • 1997
    • Hôpital Universitaire Robert Debré
      Lutetia Parisorum, Île-de-France, France