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Françoise Brun-Vézinet

Publications and source records attributed to Françoise Brun-Vézinet.

At least 19 recordsLinked to original sources
PubMed2006

Presence of numerous stop codons in HIV-1 reverse transcriptase proviral DNA sequences from patients with virological response to HAART.

The impact of proviral DNA reverse transcriptase mutations on virological failure was evaluated in 50 HIV-1 HAART-treated patients switching from a protease inhibitor to a non-nucleoside reverse transcriptase inhibitor. Neither the M184I/V mutation detected in 12 patients nor stop codons at tryptophane positions detected in 13 patients were associated with virological failure. Stop codons appeared under successful therapy in 12 patients. Their presence should be assessed in studies with higher statistical power.

Antiretroviral Therapy, Highly Active↗
PubMed2006

No association between GB virus C infection and disease progression in HIV-2-infected patients from the French ANRS HIV-2 cohort.

Out of 183 HIV-2-infected patients tested in the ANRS CO8 HIV-2 cohort, 69 were exposed to GB virus C (GBV-C), yielding a prevalence of 38% (95% CI 30.7, 45.2). There was no significant difference between the CD4 cell count and HIV-2-RNA plasma viral load in patients exposed and not exposed to GBV-C. After adjusting for age and CD4 cell count, co-infection with GBV-C was not associated with clinical progression (hazard ratio 0.78; 95% CI 0.24-2.56, 16 clinical events).

Adult↗
PubMed2006

Repeated HIV-1 resistance genotyping external quality assessments improve virology laboratory performance.

The performance of French virology laboratories belonging to the ANRS network has been assessed annually for 3 years. The performance of these laboratories was compared between the years 2002 and 2003. Ten and 7 coded samples were sent to 38 virology laboratories in 2002 and 45 virology laboratories in 2003, respectively. Each panel of coded samples included at least one HIV-negative control, a pair of duplicate specimens, samples with a wide range of viral loads, and samples with a large number of resistance mutations. The laboratories used their standard sequencing procedures and were asked to report the amino acids at codons associated with resistance mutations, based on the IAS-USA expert panel list. The reference amino acid sequences were defined as those most frequently reported by the participants. The specificity of detection of RT mutations was significantly better in 2003 (99.9%) than in 2002 (99.7%) (P = 0.05). There was no difference between 2002 and 2003 in the specificity of detection of protease mutations (99.6% and 99.8%) or the sensitivity of detection of RT mutations (98.8% and 98.2%). The sensitivity of detection of protease mutations improved significantly between 2002 and 2003 (97.6% and 99.0%, respectively; P = 0.037). The proportion of laboratories reporting fully accurate results, in terms of amplification, specificity, sensitivity, and reproducibility, tended to increase between 2002 and 2003 (P = 0.077). No errors were made by 19% of laboratories in 2002, compared to 42% in 2003. These results show the value of repeated external quality assessments.

Clinical Laboratory Techniques↗
PubMed2006

Discordances between interpretation algorithms for genotypic resistance to protease and reverse transcriptase inhibitors of human immunodeficiency virus are subtype dependent.

The major limitation of drug resistance genotyping for human immunodeficiency virus remains the interpretation of the results. We evaluated the concordance in predicting therapy response between four different interpretation algorithms (Rega 6.3, HIVDB-08/04, ANRS [07/04], and VGI 8.0). Sequences were gathered through a worldwide effort to establish a database of non-B subtype sequences, and demographic and clinical information about the patients was gathered. The most concordant results were found for nonnucleoside reverse transcriptase (RT) inhibitors (93%), followed by protease inhibitors (84%) and nucleoside RT inhibitor (NRTIs) (76%). For therapy-naive patients, for nelfinavir, especially for subtypes C and G, the discordances were driven mainly by the protease (PRO) mutational pattern 82I/V + 63P + 36I/V for subtype C and 82I + 63P + 36I + 20I for subtype G. Subtype F displayed more discordances for ritonavir in untreated patients due to the combined presence of PRO 20R and 10I/V. In therapy-experienced patients, subtype G displayed a lot of discordances for saquinavir and indinavir due to mutational patterns involving PRO 90 M and 82I. Subtype F had more discordance for nelfinavir attributable to the presence of PRO 88S and 82A + 54V. For the NRTIs lamivudine and emtricitabine, CRF01_AE had more discordances than subtype B due to the presence of RT mutational patterns 65R + 115 M and 118I + 215Y, respectively. Overall, the different algorithms agreed well on the level of resistance scored, but some of the discordances could be attributed to specific (subtype-dependent) combinations of mutations. It is not yet known whether therapy response is subtype dependent, but the advice given to clinicians based on a genotypic interpretation algorithm differs according to the subtype.

Algorithms↗
PubMed2005

Prevalence of complete resistance to at least two classes of antiretroviral drugs in treated HIV-1-infected patients: a French nationwide study.

The objective of the study was to estimate the prevalence of HIV-1 resistance to all drugs belonging to two or more antiretroviral drug (ARV) classes in treated patients in France. All genotyping assays performed in June 2001 and in November 2002 by the ANRS resistance laboratory network were analyzed by the ANRS algorithm. The 17 and 21 centers of the ANRS network participating in the study in 2001 and 2002, respectively, genotyped the viruses in plasma of 456 and 529 patients, respectively. In 2002, the proportions of patients harboring viruses fully resistant to one, two, and three ARV classes were 5.1%, 8.1%, and 2.5%, respectively. These results were similar to those obtained in 2001. In 2002, among the 56 patients with viruses completely resistant to at least two ARV classes, 98%, 96%, and 29% of patients had viruses with complete class resistance to NRTIs, NNRTIs, and PIs, respectively. Complete resistance to PIs was less frequent than full resistance to the other two ARV classes, and ritonavir-boosted amprenavir and lopinavir/r remained potentially active in respectively 71.4% and 42.9% of these 56 patients. In 2001 and 2002, respectively 30% of the 65 patients and 24% of the 56 patients with viruses completely resistant to at least two ARV classes were at an advanced stage of HIV disease, with CD4(+) cell counts below 200/microl and viral loads above 30 000 copies/ml. In France, the prevalence of HIV-1 viruses completely resistant to two or more ARV classes remained stable between 2001 and 2002. Resistance to RT inhibitors was more frequent than resistance to PIs in patients with viruses completely resistant to two or three classes of ARV.

Adolescent↗
PubMed2005

Genotypic resistance analyses in nucleoside-pretreated patients failing an indinavir containing regimen: results from a randomized comparative trial: (Novavir ANRS 073).

BACKGROUND: Different studies have shown that most patients failing a first-line treatment containing a protease-inhibitor (PI) had low PI plasma levels and no PI-related resistance mutations. NOVAVIR was a randomized trial comparing stavudine/lamivudine/indinavir (d4T/3TC/IDV) and zidovudine/lamivudine/indinavir (AZT/3TC/IDV) in patients pretreated with AZT, didanosine (ddI) and/or zalcitabine (ddC) but naive for PIs. OBJECTIVE: To study the mechanisms of virological failure in NOVAVIR trial through analyses of genotypic resistance profiles of reverse transcriptase (RT) and protease (PR), and plasma IDV concentrations at time to failure. METHODS: Plasma HIV-RNA PR and RT sequences were determined in 27 failing patients (d4T/3TC/IDV n=11; AZT/3TC/IDV n=16) at baseline and at time to failure. IDV plasma measurements were performed in both samples. RESULTS: At baseline, 20 out of the 27 patients had at least two thymidine analogs associated mutations. At time to failure, mutation M184V in the RT gene was present in 22 out of the 27 failing patients. Thirteen out of the 27 (48%) patients had acquisition of PI mutations compared to baseline sequence. Of the 26 patients with adherence data, 13 (50%) subjects were classified as having difficulty in adherence. The proportion of patients with low adherence was higher in the subgroup of patients failing without acquisition of new PI mutations. CONCLUSIONS: In patients experienced with NRTIs, failure to PI-containing regimen may occur in spite of appropriate adherence to therapy and is associated with emergence of PI mutations in half of the cases. These results suggest that, although PIs have a high genetic barrier, sub-optimal activity of associated drugs may favor the selection of PI resistance mutations.

Amino Acid Substitution↗
PubMed2005

Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021).

Tonus was a pilot study in which previously untreated human immunodeficiency virus type 1 (HIV-1)-infected patients received the combination of abacavir, lamivudine, and tenofovir once a day. There was a high rate of early virological failure, and the M184V and K65R mutations were frequently detected at week 12 (W12). The objective of this study was to examine the selection dynamics of the K65R and M184V/I mutations. Bulk sequencing of the reverse transcriptase (RT) gene was performed on plasma HIV-1 RNA at baseline, W4, and W12 for 21 patients with detectable viral loads. The RT genes from baseline, W4, and W12 plasma samples from five patients who developed both M184V and K65R but with different mutational patterns were also cloned and screened for the K65R mutation by selective real-time PCR. At baseline, bulk sequencing and clonal analysis showed only wild-type RT sequences. At W4, M184V/I was detected in 12/19 patients and K65K/R in 2 patients by bulk sequencing. At W12, M184V/I was found in 18/20 patient, together with the K65R in 13 patients. At W4, clonal analysis revealed the K65R mutation in 0.6 to 48% of clones in the five patients studied. At W12, the K65R mutation was found in 30 to 100% of clones. K65R and M184V/I seemed to arise in separate clones, followed by an enrichment of viruses containing both mutations. The clinical relevance of this independent evolution is unclear. M184V/I was selected more frequently than K65R at W4. However, K65R was also detected early using a clone-sensitive genotyping method. All three nucleoside analogs are known to select the K65R and/or M184V/I mutation. This convergent genetic pathway to resistance, associated with lower antiretroviral potency, may explain the high selection rate of these mutations in this trial.

Adenine↗
PubMed2005

Letter. In vitro phenotypic susceptibility to nucleoside reverse transcriptase inhibitors of HIV-2 isolates with the Q151M mutation in the reverse transcriptase gene.

In HIV-2 infection, many studies have reported a high frequency of selection of the Q151M mutation, but its impact on phenotypic susceptibility of HIV-2 isolates remains unclear. Four HIV-2 infected patients from the French ANRS HIV-2 cohort, with evidence of Q151M mutation in both plasma and available peripheral blood mononuclear cells (PBMCs) co-cultivated supernatants, were selected. In vitro phenotypic susceptibilities to different nucleoside reverse transcriptase inhibitors (NRTIs) were determined using a PBMC assay. In HIV-2 isolates, the Q151M mutation alone impacts only the phenotypic susceptibility to stavudine and abacavir. A decrease in susceptibility to all NRTIs was observed when Q151M was selected with V111I, a mutation of unknown impact on HIV-1 resistance. Clinical relevance of these phenotypic susceptibility results needs to be evaluated in HIV-2 treated patients.

Drug Resistance, Multiple, Viral↗
PubMed2004

Identification of a highly divergent HIV type 2 and proposal for a change in HIV type 2 classification.

We report the complete genome sequence of a highly divergent strain of human immunodeficiency virus type 2 (HIV-2), 96FR12034, identified in France from a patient of West African origin. This lineage, H, represents only the third definitive instance of a monkey-to-human transfer of SIVsm that has given rise to pathogenic HIV-2. As the different "subtypes" of HIV-2 are analogous to the different groups of HIV-1 we propose that HIV-2 subtypes henceforth by renamed groups in agreement with the HIV Nomenclature Committee. The single-strain lineages C to G and the 96FR12034 lineage identified here should be considered only as putative groups until related strains are identified that confirm circulation of these viruses in the human population.

Adult↗
PubMed2004

Rapid discrimination between human immunodeficiency virus type 2 groups A and B by real-time PCR.

We studied the feasibility of genotyping human immunodeficiency virus (HIV) type 2 groups A and B by real-time PCR. Two group-specific PCRs were developed. Real-time genotyping of 22 samples of genotype A, 10 samples of genotype B, and the isolate of new group H were compared to genotyping by sequencing and phylogeny. The group-specific PCRs specifically identified 84.3% of group A or B samples; isolate H was not detected. This method allowed rapid and specific discrimination between HIV-2 groups A and B and could be a useful tool for molecular epidemiological studies.

Genotype↗
PubMed2004

Genotypic determinants of the virological response to tenofovir disoproxil fumarate in nucleoside reverse transcriptase inhibitor-experienced patients.

OBJECTIVE: To assess the genotypic determinants of the virological response to tenofovir disoproxil fumarate (TDF) in a multicentre cohort of antiretroviral (ARV)-experienced patients receiving TDF as a part of a salvage therapy. METHODS: HIV-1 genotype was assessed at baseline in a subgroup of 161 patients of the French expanded access program receiving a stable TDF-including regimen for 3 months or more. Reverse transcriptase mutations associated with the viral load decrease at month 3 with a P-value <0.15 were retained for the construction of a mutation score. The score was then validated using a multivariate analysis and bootstrap resampling method. RESULTS: The strongest association with decrease in viral load was observed with a set of seven mutations (TDF mutation score) that consisted of M41L, E44D, D67N, T69D/N/S, L74V, L210W and T215Y/F RT mutations. The RT K65R mutation and the insertions at codon 69 were not included in the analysis due to low prevalences. A TDF mutation score of < or = 2 predicted the absence of resistance to TDF and > or = 6 mutations predicted resistance to TDF with corresponding reductions in viral load of -1.3 +/- 1.1, and +0.1 +/- 0.7 log10 copies/ml, respectively. In patients with a TDF mutation score of 3-5, the decrease in viral load was -0.8 +/- 1.0 log10 copies/ml and was considered possibly resistant. In the multivariate analysis, a TDF mutation score > or = 6, previous use of amprenavir, indinavir and lopinavir, and co-prescription of didanosine were associated with a worse virological response. The bootstrap analysis showed the robustness of the TDF mutation score. CONCLUSION: In ARV-experienced patients receiving TDF-containing regimens, a score derived from seven reverse transcriptase mutations was shown to be independently predictive of the virological response.

Adenine↗
PubMed2004

Clinically validated genotype analysis: guiding principles and statistical concerns.

Whereas previously the output of HIV resistance tests has been based on therapeutically arbitrary criteria, there is now an ongoing move towards correlating test interpretation with virological outcomes on treatment. This approach is undeniably superior, in principle, for tests intended to guide drug choices. However the predictive accuracy of a given stratagem that links genotype or phenotype to drug response is strongly influenced by the study design, data capture and analytical methodology used to derive it. For genotyping, the most widely used resistance tool in clinical practice, these considerations are further complicated by the range of mutational patterns present in the treated population. There is no definitively superior methodology for generating a genotype-response association for use in interpreting a resistance test, and the various approaches used to date all have their strengths and weaknesses. This review discusses the processes involved in constructing such tools, with particular emphasis on establishing validated mutation score rules, and examines the key issues and confounding factors that influence predictive accuracy outside the originating dataset. Since the size of the sample is a key influence on the statistical power to determine an effect, it is hoped that a greater understanding of the influence of study design and methodology will assist the development of standardized outcome measures and reporting formats that allow data pooling at the international level.

Anti-HIV Agents↗
PubMed2003

Clinically relevant interpretation of genotype for resistance to abacavir.

OBJECTIVE: To develop a stepwise methodology for the development and validation of clinically relevant genotypic score for resistance to antiretroviral drugs and to apply this approach to the genotypic resistance to abacavir. METHODS: All patients having received abacavir during the Narval trial were included in this study. The impact of each nucleoside analogue resistance mutation on the virologic response to abacavir was studied in a univariate analysis. Mutations with a P value < 0.20 and those selected by abacavir were retained. According to the number of mutations three levels of resistance were defined. A multivariate analysis accounting for confonding variables assessed whether the genotypic score was an independent predictor of the response. The robustness of the score was analysed using the bootstrap resampling method. RESULTS: In the 175 patients exposed to abacavir, the strongest association between the decrease in viral load and the number of mutations was observed with a set of six mutations at codons 41, 67, 210, 215, 74 and 184 of the reverse transcriptase gene. In patients with fewer than four mutations (no evidence of resistance) the median decrease in viral load was -1.64 log(10) copies/ml while it was -0.69 log(10) and -0.19 log(10) in those with four (possible resistance) and five or six (resistance) mutations respectively. In the multivariate analysis this score was an independent predictor of the response. The bootstrap analysis showed the robustness of the score. CONCLUSIONS: We developed a new strategy for the analysis of correlation between genotype profile at baseline and virologic response.

Algorithms↗
PubMed2003

Antiretroviral drug resistance testing in adults infected with human immunodeficiency virus type 1: 2003 recommendations of an International AIDS Society-USA Panel.

New information about the benefits and limitations of testing for resistance to human immunodeficiency virus (HIV) type 1 (HIV-1) drugs has emerged. The International AIDS Society-USA convened a panel of physicians and scientists with expertise in antiretroviral drug management, HIV-1 drug resistance, and patient care to provide updated recommendations for HIV-1 resistance testing. Published data and presentations at scientific conferences, as well as strength of the evidence, were considered. Properly used resistance testing can improve virological outcome among HIV-infected individuals. Resistance testing is recommended in cases of acute or recent HIV infection, for certain patients who have been infected as long as 2 years or more prior to initiating therapy, in cases of antiretroviral failure, and during pregnancy. Limitations of resistance testing remain, and more study is needed to refine optimal use and interpretation.

Adult↗
PubMed2003

HIV type 1 diversity in northeastern Romania in 200-2001 based on phylogenic analysis of pol sequences from patient failing antiretroviral therapy.

Protease and the first half of reverse transcriptase from 71 Romanian patients failing highly active antiretroviral therapy (HAART) have been sequenced and phylogenetically analyzed. These analyses show that 70 patients were infected with subtype F1 and one with subtype C. The pattern of drug resistance mutations in subtype F1-infected patients failing HAART is similar to that described for subtype B strains. These results show that the diversity pattern of HIV type 1 infection in Romania has remained steady over a decade, with subtype F1 remaining the predominant viral form. The circulation of subtype F1 in Romania has the potential to be a source of this HIV-1 subtype in Europe..

Adolescent↗
PubMed2003

R57K polymorphism in the human immunodeficiency virus type 1 protease as predictor of early virological failure in a cohort of antiretroviral-naive patients treated mostly with a nelfinavir-containing regimen.

In 243 antiretroviral-naive human immunodeficiency-infected patients starting a first-line-protease inhibitor (mainly nelfinavir)-containing therapy, the presence of the polymorphism R57K in the protease at the inception of therapy was independently associated with a higher rate of virological failure.

Adult↗