A G Marcelin

Unité Inserm U1077, Caen, Lower Normandy, France

Are you A G Marcelin?

Claim your profile

Publications (84)376.12 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Several genotypic rules for predicting HIV-1 non-B subtypes tropism are commonly used, but there is no consensus about their performances. Objectives: Three genotypic methods were compared for CRF02_AG HIV-1 tropism determination. Study design: V3 env region of 178HIV-1 CRF02_AG from Pitié-Salpêtrière and Saint-Antoine Hospitals was sequenced from plasma HIV-1 RNA. HIV-1 tropism was determined by Geno2Pheno algorithm, false positive rate (FPR) 5% or 10%, the 11/25 rule or the combined criteria of the 11/25 and net charge rule. Results: A concordance of 91.6% was observed between Geno2pheno 5% and the combined criteria. The results were nearly similar for the comparison between Geno2pheno 5% and the 11/25 rule. More mismatches were observed when Geno2pheno was used with the FPR 10%. A lower nadir CD4 cell count was associated with a discordance of tropism prediction between Geno2pheno 5% and the combined criteria or the 11/25 rule (p=0.02 and p=0.03, respectively). A lower HIV-1 viral load was associated with some discordance for the comparison of Geno2pheno 10% and the combined rule (p=0.02). Conclusion: Geno2pheno FPR 5% or 10% predicted more X4-tropic viruses for this set of CRF02_AG sequences than the combined criteria or the 11/25 rule alone. Furthermore, Geno2pheno FPR 5% was more concordant with the 11/25 rule and the combined rule than Geno2pheno 10% to predict HIV-1 tropism. Overall, Geno2pheno 5% could be used to predict CRF02_AG tropism as well as other genotypic rules.
    No preview · Article · Jan 2016 · Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: To describe the pattern of drug resistance at virological failure in the NEAT001/ANRS143 trial (first-line treatment with ritonavir-boosted darunavir plus either tenofovir/emtricitabine or raltegravir). Methods: Genotypic testing was performed at baseline for reverse transcriptase (RT) and protease genes and for RT, protease and integrase (IN) genes for patients with a confirmed viral load (VL) >50 copies/mL or any single VL >500 copies/mL during or after week 32. Results: A resistance test was obtained for 110/805 (13.7%) randomized participants qualifying for resistance analysis (61/401 of participants in the raltegravir arm and 49/404 of participants in the tenofovir/emtricitabine arm). No resistance-associated mutation (RAM) was observed in the tenofovir/emtricitabine plus darunavir/ritonavir arm, and all further analyses were limited to the raltegravir plus darunavir arm. In this group, 15/55 (27.3%) participants had viruses with IN RAMs (12 N155H alone, 1 N155H + Q148R, 1 F121Y and 1 Y143C), 2/53 (3.8%) with nucleotide analogue RT inhibitor RAMs (K65R, M41L) and 1/57 (1.8%) with primary protease RAM (L76V). The frequency of IN mutations at failure was significantly associated with baseline VL: 7.1% for a VL of <100 000 copies/mL, 25.0% for a VL of ≥100 000 copies/mL and <500 000 copies/mL and 53.8% for a VL of ≥500 000 copies/mL (PTREND = 0.007). Of note, 4/15 participants with IN RAM had a VL < 200 copies/mL at time of testing. Conclusions: In the NEAT001/ANRS143 trial, there was no RAM at virological failure in the standard tenofovir/emtricitabine plus darunavir/ritonavir regimen, contrasting with a rate of 29.5% (mostly IN mutations) in the raltegravir plus darunavir/ritonavir NRTI-sparing regimen. The cumulative risk of IN RAM after 96 weeks of follow-up in participants initiating ART with raltegravir plus darunavir/ritonavir was 3.9%.
    No preview · Article · Dec 2015 · Journal of Antimicrobial Chemotherapy
  • Source

    Full-text · Article · Sep 2015 · Médecine et Maladies Infectieuses
  • [Show abstract] [Hide abstract]
    ABSTRACT: An incomplete Apobec3G/F neutralization by defective HIV-1Vif protein can promote genetic diversification, by inducing G-to-A mutations along HIV-1 genome. The HIV-1 Env V3 loop, critical for co-receptor usage, contains several putative Apobec3G/F target sites. Here, we determined if Apobec3G/F, in presence of Vif-defective HIV-1 virus, can induce G-to-A mutations at V3 positions critical to modulate CXCR4-usage.PBMC and monocyte-derived-macrophages (MDM) from 2 HIV-1 negative donors were infected by CCR5-using 81.A-Vifwt, 81.A-VifE45G-mutant, and 81.A-VifK22E-mutant (known to incompletely/partially neutralize Apobec3G/F). The rate of G-toAs was null or extremely low in 81.A-Vifwt and 81.A-VifE45G infected PBMC from both donors. Conversely, a G-to-As enrichment was detected in 81.A-VifK22E infected PBMC (prevalence ranging from 2.18% at 7dpi to 3.07% at 21dpi in donor #1, and from 10.49% at 7dpi to 8.69% at 21dpi in donor #2). A similar scenario was found in MDM.G-to-As occurred at 8 V3 positions, resulting in amino acid non-synonymous substitutions. Of them, G24E and E25K strongly correlated with phenotypically/genotypically defined CXCR4-using viruses (P-value = 0.04 and 5.5e-7), and increased CXCR4 N-terminus binding affinity for V3 (WT: -40.1Kcal/mol; G24E: -510Kcal/mol; E25K: -522Kcal/mol).The analysis of paired V3 and Vif DNA sequences from 84 HIV-1 infected patients showed that the presence of a Vif-defective virus correlated with a CXCR4-usage in proviral DNA (P-value=0.04). In conclusion, incomplete Apobec3G/F neutralization by single Vif amino acid substitution seeds a CXCR4-using proviral reservoir. This can have implications for the success of CCR5 antagonist-based therapy, as well as for the risk of disease progression. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    No preview · Article · Jun 2015 · Antimicrobial Agents and Chemotherapy
  • [Show abstract] [Hide abstract]
    ABSTRACT: Virological failure (VF) in patients on maraviroc-based treatment has been associated with altered HIV tropism and resistance to maraviroc. This multicentre study aimed to characterize VF in patients treated with maraviroc. We analysed 27 patients whose treatment failed between 2008 and 2011. They had been screened for HIV tropism before maraviroc initiation using population-based V3 genotyping. HIV-1 tropism and resistance of R5 viruses to maraviroc at VF and at baseline were determined retrospectively using an ultrasensitive recombinant virus assay (RVA). Viruses from 27 patients given maraviroc on the basis of the R5 genotype were characterized at the time of treatment failure. The RVA indicated that 12 patients harboured CXCR4-using viruses and 15 (56%) had pure R5 viruses at failure. One-third of those harbouring CXCR4-using viruses (4/12) were infected with R5X4/X4 viruses according to the RVA before maraviroc initiation. We analysed the phenotypic resistance to maraviroc of four patients harbouring R5 viruses at failure; two harboured viruses whose maximum percentage inhibition was reduced by 65%-90%, while the other two were infected with susceptible viruses. All patients had effective concentrations of drugs. Half of the maraviroc-treated patients who experienced VF harboured CXCR4-using viruses at failure, one-third of them were detected by a phenotypic method before maraviroc initiation. Phenotypic assessment of R5 virus resistance to CCR5 antagonists at failure could help optimize antiretroviral therapy. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    No preview · Article · Feb 2015 · Journal of Antimicrobial Chemotherapy
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives This observational study in antiretroviral treatment-experienced, HIV-1-infected adults explored the efficacy of etravirine plus darunavir/ritonavir (DRV group; n = 999) vs. etravirine plus an alternative boosted protease inhibitor (other PI group; n = 116) using pooled European cohort data.Methods Two international (EuroSIDA; EUResist Network) and five national (France, Italy, Spain, Switzerland and UK) cohorts provided data (collected in 2007–2012). Stratum-adjusted (for confounding factors) Mantel–Haenszel differences in virological responses (viral load < 50 HIV-1 RNA copies/mL) and odds ratios (ORs) with 95% confidence intervals (CIs) were derived.ResultsBaseline characteristics were balanced between groups except for previous use of antiretrovirals (≥ 10: 63% in the DRV group vs. 49% in the other PI group), including previous use of at least three PIs (64% vs. 53%, respectively) and mean number of PI resistance mutations (2.3 vs. 1.9, respectively). Week 24 responses were 73% vs. 75% (observed) and 49% vs. 43% (missing = failure), respectively. Week 48 responses were 75% vs. 73% and 32% vs. 30%, respectively. All 95% CIs around unadjusted and adjusted differences encompassed 0 (difference in responses) or 1 (ORs). While ORs by cohort indicated heterogeneity in response, for pooled data the difference between unadjusted and adjusted for cohort ORs was small.Conclusions These data do not indicate a difference in response between the DRV and other PI groups, although caution should be applied given the small size of the other PI group and the lack of randomization. This suggests that the efficacy and virology results from DUET can be extrapolated to a regimen of etravirine with a boosted PI other than darunavir/ritonavir.
    Full-text · Article · Feb 2015 · HIV Medicine

  • No preview · Article · Jan 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: There are few data on the clinical and virological factors associated with maraviroc (MVC) virological response (VR) in clinical practice. This study aimed to identify factors associated with VR to MVC-containing regimens in 104 treatment-experienced but CCR5 inhibitor-naive HIV-1 patients. VR was defined at Month 3 (M3) as HIV-1 RNA viral load (VL) <50 copies/mL. The impact on VR of age, sex, baseline tropism, HIV subtype (B vs non-B), nadir CD4 cell count and CD4 cell count, baseline VL, genotypic susceptibility score of treatment, once or twice daily treatment, presence of raltegravir in optimized background therapy and MVC concentrations was investigated. Median baseline VL was 3.3 log10 copies/mL (range 1.7-6.0 log10 copies/mL) and CD4 cell count was 299 cells/mm3 (range 7-841 cells/mm3). At M3, 53.8% of patients were responders. In univariate analysis, a better efficacy of MVC-containing regimen was associated with a high CD4 cell count (p=0.0069) and there was a trend for low baseline VL, high nadir CD4 cell count and HIV subtype (B versus non B). Only low baseline VL remained significantly associated with better VR in the multivariate analysis. This study demonstrated a VR of an optimized antiretroviral treatment including MVC in clinical practice similar to that observed in clinical trials. The factors associated with VR were higher baseline CD4 cell count in univariate analysis and lower baseline VL in multivariate analysis.
    No preview · Article · Nov 2014 · AIDS Research and Human Retroviruses
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: In resource-limited settings, few data are available on virological failure after long-term first-line antiretroviral therapy. This study characterized the genotypic resistance patterns at the time of failure after at least 36 months of a first-line regimen in Mali, West Africa. Methods: Plasma samples from 84 patients who were receiving first-line antiretroviral treatment and with an HIV-1 RNA viral load (VL) >1000 copies/mL were analysed. Genotypic resistance testing was performed and HIV-1 drug resistance was interpreted according to the latest version of the National Agency for HIV and Hepatitis Research algorithm. Results: At the time of resistance testing, patients had been treated for a median of 60 months (IQR 36-132 months) and had a median CD4 cell count of 292 cells/mm(3) (IQR 6-1319 cells/mm(3)), a median HIV-1 RNA level of 28266 copies/mL (IQR 1000-2 93 495 copies/mL) and a median genotypic susceptibility score of 1 (IQR 1-4). The prevalence of nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations was 78% and 82%, respectively. Viruses were resistant to at least one drug in 92% of cases. Although etravirine and rilpivirine were not used in the first-line regimens, viruses were resistant to etravirine in 34% of cases and to rilpivirine in 49% of cases. The treatment duration, median number of NRTI and NNRTI mutations and some reverse transcriptase mutations (T215Y/F/N, L210W, L74I, M41L and H221Y) were associated with the VL at virological failure. Conclusions: This study demonstrated a high level of resistance to NRTIs and NNRTIs, compromising second-generation NNRTIs, for patients who stayed on long-term first-line regimens. It is crucial to expand the accessibility of virological testing in resource-limited settings to limit the expansion of resistance and preserve second-line treatment efficacy.
    Preview · Article · May 2014 · Journal of Antimicrobial Chemotherapy

  • No preview · Conference Paper · Jan 2014

  • No preview · Conference Paper · Jan 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the context of simplification strategies, it is essential to know the feasibility of a switch to a rilpivirine-based therapy. The aim of this study was to describe rilpivirine, tenofovir and emtricitabine resistance in HIV-1-infected patients who experienced virological failure during their previous antiretroviral treatment. The studied population included two groups of patients, all rilpivirine naive, tested for resistance by bulk sequencing from 2008 to 2011: the first group (n = 998) failing a nucleoside reverse transcriptase inhibitor (NRTI) plus boosted protease inhibitor (PI)-based regimen and the second group (n = 3733) failing an NRTI plus non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. In the first group, the frequency of rilpivirine mutations and resistance to rilpivirine (5.1%) was similar to that in antiretroviral-naive HIV-1-infected patients. Among the 1605 patients from the second group with at least one NNRTI mutation in their HIV, the prevalence of viruses 'resistant' or 'possibly resistant' to efavirenz, nevirapine and etravirine was 78%, 79% and 74%, respectively, while 59% were resistant to rilpivirine. Resistance to rilpivirine was significantly more frequent in non-B subtype versus B subtype viruses. Among pretreated patients with viruses with at least one NNRTI mutation (other than for rilpivirine), 22% of sequences were susceptible to the combination rilpivirine/emtricitabine/tenofovir disoproxil fumarate. In patients failing an NRTI plus NNRTI-based regimen, to know the feasibility of a switch to rilpivirine/emtricitabine/tenofovir disoproxil fumarate, reliable resistance information should be available at the time of use of concurrent NNRTI therapy.
    No preview · Article · Dec 2013 · Journal of Antimicrobial Chemotherapy
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: As recommended by the French ANRS programme for the surveillance of HIV-1 resistance, we estimated the prevalence of transmitted drug resistance-associated mutations (RAMs) in antiretroviral-naive, chronically HIV-1-infected patients. Methods: RAMswere sought in samples from661 newly diagnosed HIV-1-infected patients in 2010/11 at 36 HIVclinical care centres.Weighted analyses were used to derive representative estimates of the percentage of patients with RAMs. Results: At patient inclusion, the prevalence of viruswith protease (PR) or reverse transcriptase (RT) RAMswas 9.0%(95% CI 6.8%-11.2%). No integrase RAMs were observed. The prevalences of protease inhibitor, nucleoside RT inhibitor and non-nucleoside RT inhibitor RAMs were 1.8%, 6.2% and 2.4%, respectively. Resistance to one, two and three classes of antiretroviral agent was observed in 7.9%, 0.9% and 0.2% of patients, respectively. The frequency of RAMs was higher in patients infected with B compared with non-B subtype virus (11.9% versus 5.1%, P=0.003). Baseline characteristics (gender, age, country of transmission, CD4 cell count and viral load)were not associated with the prevalence of transmitted RAMs. However, men having sex with men (MSM)were more frequently infected with resistant virus than were other transmission groups (12.5%versus5.8%,P=0.003).Compared with the 2006/07 survey, the over all prevalence of resistance remained stable. However, a significant decrease in the frequency of virus with PRRAMs was observed in 2010/11 compared with the 2006/07 survey (1.8%versus 5.0%, P=0.003). Conclusions: In France in 2010/11, the global prevalence of transmitted drug-resistant variants was 9.0%, and the prevalence was stable compared with the 2006/07 survey. MSM and B subtype-infected patients are the groupswith a higher prevalence of drug resistance. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
    Full-text · Article · Nov 2013 · Journal of Antimicrobial Chemotherapy
  • [Show abstract] [Hide abstract]
    ABSTRACT: The lack of antiretroviral (ARV) backbone activity associated with raltegravir has been proposed as the main explanation for virological relapse observed in patients with undetectable viraemia who are switched from a ritonavir-boosted protease inhibitor (PI) to raltegravir. However ARV activity remains difficult to assess in this context. The aim of our study was to precisely assess the ARV backbone activity in patients with undetectable viraemia who underwent raltegravir switching strategies and to evaluate the efficacy of such switching strategies based on the genotypic sensitivity score (GSS). Patients with a plasma human immunodeficiency virus type 1 (HIV-1) RNA level of <50 copies/mL on a stable two ARV-class regimen were enrolled if they switched one of their ARV drugs to raltegravir 400 mg twice daily. The GSS was calculated using a genotyping test performed on the HIV-1 RNA of the last plasma measurement with a HIV-1 RNA level of >50 copies/mL before the switch and on the results of all previous genotyping tests. The primary endpoint was the proportion of patients with a plasma HIV-1 RNA level of <50 copies/mL at week 24. Fifty-six patients were enrolled in this study. The proportion of patients with a plasma HIV-1 RNA level of <50 copies/mL at week 24 was 92.9 % (range 83.0-97.2 %) in the intent-to-treat analysis and 98.1 % (90.0-99.7 %) in per-protocol analysis. When the backbone was fully active, the proportion was 100.0 % (86.7-100.0 %) at week 24 and week 48 in the per-protocol analysis. We observed a decrease in plasma total cholesterol and triglycerides of -12.7 % (p = 0.005) and -26.5 % (p = 0.001), respectively. Raltegravir switching strategies are effective when the associated backbone is fully active according to the GSS. In the context of undetectable viraemia, where ARV activity remains difficult to assess, the determination of the GSS requires the entire ARV history of the patient and all previous HIV-RNA genotyping test results.
    No preview · Article · Oct 2013 · Infection
  • Source

    Full-text · Article · Aug 2013 · JAIDS Journal of Acquired Immune Deficiency Syndromes
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It has been demonstrated for some drugs that the genetic barrier, defined as the number of genetic transitions and/or transversions needed to produce a resistance mutation, can differ between HIV-1 subtypes. We aimed to assess differences in the genetic barrier for the evolution of resistance to the second-generation non-nucleoside reverse transcriptase inhibitors etravirine and rilpivirine in subtypes B and CRF02_AG in antiretroviral-naive patients. An analysis was undertaken of 25 substitutions associated with etravirine and rilpivirine resistance at 12 amino acid positions in 267 nucleotide sequences (136 HIV-1 B and 131 HIV-1 CRF02_AG subtypes) of the reverse transcriptase gene. The majority (7/12) of amino acid positions studied were conserved between the two HIV-1 subtypes, leading to a similar genetic barrier. Different predominant codons between the subtypes were observed in 5/12 positions (90, 98, 179, 181 and 227), with an effect on the calculated genetic barrier only at the V179D and V179F codons (2.5 versus 3.5 for V179D, and 2.5 versus 5 for V179F, respectively, for subtype B versus subtype CRF02_AG). The majority of amino acids involved in etravirine and rilpivirine resistance showed a high degree of conservation of the predominant codon between the B and CRF02_AG subtypes. For rilpivirine, the genetic barrier was the same between the two subtypes. Nevertheless, subtype CRF02_AG showed a higher genetic barrier to acquiring mutations V179D and V179F (mutations associated with resistance to etravirine) compared with subtype B, suggesting that it would be more difficult to produce resistance to etravirine in the CRF02_AG subtype than the B subtype.
    Preview · Article · Jul 2013 · Journal of Antimicrobial Chemotherapy
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background. The induction of neutralizing antibodies against conserved regions of the HIV-1 envelope protein is a major goal of vaccine strategies. We previously identified 3S, a critical conserved motif of gp41 that induces the NKp44&emsp14;L ligand of an activating NK receptor. In vivo, anti-3S antibodies protect against the NK-cell mediated CD4 depletion that occurs without efficient viral neutralization. Methods. Specific substitutions within the 3S peptide motif were prepared by directed mutagenesis. Virus production was monitored by measuring the p24 production. Neutralization assays were performed with immune-purified antibodies from immunized mice and a cohort of HIV-infected patients. Expression of NKp44&emsp14;L on CD4+ T cells and degranulation assay on activating NK cells were both performed by flow cytometer. Results. Here, we show that specific substitutions in the 3S motif reduce viral infection without affecting gp41 production, while decreasing both its capacity to induce NKp44&emsp14;L expression on CD4+ T cells and its sensitivity to autologous NK cells. Generation of antibodies in mice against the W614 specific position in the 3S motif elicited a capacity to neutralize cross-clade viruses, notable in its magnitude, breadth and durability. Antibodies against this 3S variant were also detected in sera from some HIV-1 infected patients, demonstrated both neutralization activity and protection against CD4 depletion. Conclusions. These findings suggest that a specific substitution in a 3S-based immunogen might allow the generation of specific antibodies, providing a foundation for a rational vaccine that combine a capacity to neutralize HIV-1 and to protect CD4+ T cells.
    No preview · Article · May 2013 · Clinical Infectious Diseases
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human herpes virus 8 (HHV-8) is an oncogenic gamma-herpes virus first described in 1994 in Kaposi sarcoma (KS) lesions. HHV-8 is involved in the pathophysiologic features of multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL), both rare B-cell lymphoproliferative diseases. HHV-8-related tumours occur almost exclusively in immunocompromised patients, most with HIV infection. Combined antiretroviral therapies have reduced the incidence of KS but not MCD and PEL. HHV-8-related diseases frequently exhibit pulmonary involvement, which may indicate the disease. KS in the lung is often asymptomatic but may require specific therapy. It mostly shows cutaneous or mucosal involvement. Patients with typical MCD present fever and lymphadenopathy associated with interstitial lung disease without opportunistic infection. Specific treatment may be urgent. PEL provokes a febrile, lymphocytic-exudative pleural effusion, without pleural mass on CT scan. Rapid diagnosis prevents unnecessary exams and leads to specific, rapid treatment. Therapy is complex, combining antiretroviral therapy and chemotherapy.
    Preview · Article · Feb 2013 · European Respiratory Journal
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There is evidence that HIV-1 evolution under maraviroc (MVC) pressure can lead to the selection of either X4-tropic variants and/or R5-tropic, MVC-resistant isolates. However, the viral dynamics of HIV-1 variants in patients with virological failure (VF) on MVC-containing regimens remain poorly studied. Here, we investigated the V3 loop evolution of HIV-1 on MVC in relation to coreceptor usage and the nature of HIV-1 quasispecies before MVC therapy using bulk population sequences and ultradeep sequencing. The majority of patients had no detectable minority X4 variant at baseline. The evolution of tropism was followed up until VF and showed three possibilities for viral evolution in these patients: emergence of preexisting X4 variants, de novo selection of R5 variants presenting V3 loop mutations, or replication of R5 variants without selection of known mutations.
    Full-text · Article · Feb 2013 · Antimicrobial Agents and Chemotherapy
  • [Show abstract] [Hide abstract]
    ABSTRACT: To treat human immunodeficiency virus (HIV)-infected patients, international guidelines recommend the combination of two nucleos(t)ide reverse transcriptase inhibitors [N(t)RTIs] and a third agent [non-NRTI (NNRTI), boosted protease inhibitor (r/PI) or integrase inhibitor (INI)] for initial treatment. The objective of this study was to compare the selection of resistance to antiretrovirals (ARVs) for regimens containing or lacking N(t)RTIs in patients experiencing their first virological failure. Eligible patients had a first virological failure, defined as the occurrence of two consecutive HIV plasma viral loads ≥50 copies/mL. Genotypic resistance testing was performed at the time of virological failure (on the second sample with detectable viral load ≥50 copies/mL) in patients failing regimens of N(t)RTIs + r/PI or NNRTI or INI, r/PI + NNRTI or INI, and INI + NNRTI. Among 434 virological failures analysed, resistance testing results were available in 416 cases (95.9%). Higher rates of drug resistance were observed in patients receiving N(t)RTI-sparing regimens. When the combination of N(t)RTIs + r/PI was used, PIs protect themselves and the associated N(t)RTIs from the selection of resistance; however, this was not observed with the NNRTI + r/PI combination. The same phenomenon was observed for raltegravir: when used in combination with N(t)RTIs, INI resistance mutations were less frequently selected compared with its use in combination with PIs or NNRTIs. In conclusion, regimens of the ARV classes combined impact the frequency of resistance development. Lower resistance is observed for N(t)RTI-based regimens, with more therapeutic options for subsequent regimens after failure.
    No preview · Article · Jan 2013 · Journal of Global Antimicrobial Resistance

Publication Stats

1k Citations
376.12 Total Impact Points

Institutions

  • 2010-2016
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2015
    • Bordeaux School of Public Health
      Burdeos, Aquitaine, France
  • 2011-2015
    • Polytech Paris-UPMC
      Lutetia Parisorum, Île-de-France, France
  • 2010-2015
    • Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix
      Lutetia Parisorum, Île-de-France, France
  • 1999-2015
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      • Service de Virologie
      Lutetia Parisorum, Île-de-France, France
  • 2010-2013
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2007-2013
    • Pierre and Marie Curie University - Paris 6
      • Faculté de médecine Pierre et Marie Curie
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • ANRS - Agence Nationale de Recherche sur le Sida et les hépatites virales
      Lutetia Parisorum, Île-de-France, France
  • 2004
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      Lutetia Parisorum, Île-de-France, France
  • 2002
    • Chelsea and Westminster Hospital NHS Foundation Trust
      Londinium, England, United Kingdom