The build-up of stock of stable integrated proviruses overtime explains the difficulty in reducing HIV-1 DNA levels when treatment is initiated at the chronic stage of the infection.

Background: Understanding factors affecting the size and the evolution of the HIV reservoir is essential for the development of curative strategies. This study aimed to assess the impact of antiretroviral therapy (ART) initiated during primary infection (PHI) chronic infection (CHI) on the levels and dynamics of integrated HIV-1 DNA, a biomarker of viral persistence.

Methods: Integrated and total HIV-1-DNA were measured in the blood of 92 patients treated during PHI (early group) and 41 during CHI (deferred group), at diagnosis, ART initiation, and 12-24 months on treatment.

Once-daily dolutegravir versus darunavir plus cobicistat in adults at the time of primary HIV-1 infection: the OPTIPRIM2-ANRS 169 randomized, open-label, Phase 3 trial.

Background: Whether integrase strand transfer inhibitors (INSTIs) can decrease HIV-1 DNA levels more rapidly than boosted PIs during primary HIV-1 infection (PHI) is unknown. We hypothesized that once-daily dolutegravir/tenofovir/emtricitabine could reduce the viral reservoir through rapid viral replication control further than once-daily darunavir/cobicistat/tenofovir/emtricitabine.

Methods: The OPTIPRIM2-ANRS 169 study was a randomized (1:1), open-label, multicentre trial in adults with ≤5 or ≤3 HIV antibodies detected, respectively, by western blot or immunoblot in the last 10 days.

Immunogenicity and safety of yellow fever vaccine in HIV-1-infected patients.

Objectives: The objective of this study is to investigate immunogenicity and safety of the yellow fever vaccine (YFV) in HIV-infected (HIV+) patients with high CD4 T-cell counts.

Design: In this prospective, comparative study of YFV-naive adults: 40 HIV+ under antiretroviral therapy (ART) with CD4 T-cell count above 350 cells/μl and plasma HIV-RNA less than 50 copies/ml for at least 6 months and 31 HIV-negative (HIV-) received one injection of the YF-17D strain vaccine.

Methods: Serologic response was assessed by using a plaque reduction neutralizing test and YFV-specific T cells by using an INFγ-Elispot assay.

Screening test for neutralizing antibodies against yellow fever virus, based on a flavivirus pseudotype.

Given the possibility of yellow fever virus reintroduction in epidemiologically receptive geographic areas, the risk of vaccine supply disruption is a serious issue. New strategies to reduce the doses of injected vaccines should be evaluated very carefully in terms of immunogenicity. The plaque reduction test for the determination of neutralizing antibodies (PRNT) is particularly time-consuming and requires the use of a confinement laboratory.

Effect of two injections of non-adjuvanted influenza A H1N1pdm2009 vaccine in renal transplant recipients: INSERM C09-32 TRANSFLUVAC trial.

Background: Enhancing vaccine immunogenicity in kidney transplant recipients, particularly against influenza, is required since the immunosuppression used to prevent graft rejection limits vaccine immunogenicity. We therefore investigated the immunogenicity and safety of a double dose non-adjuvanted vaccination regimen against influenza H1N1pdm2009 in kidney transplant adult recipients.

Methods: A prospective single-arm study was conducted including 121 renal transplant recipients under triple immunosuppressive regimen.

Incidence and risk factors of thrombocytopenia in patients receiving intermittent antiretroviral therapy: a substudy of the ANRS 106-window trial.

Background: Incidence and risk factors for thrombocytopenia in patients discontinuing highly active antiretroviral therapy (HAART) have not been fully investigated.

Methods: Well-suppressed patients on HAART were randomized to continuous (CT) or intermittent therapy (IT) for 96 weeks. Incidence of thrombocytopenia (<150 x 10(3) platelets/mm(3)) was assessed and multivariate analysis performed to identify baseline predictors.

Interruption of antiretroviral therapy initiated during primary HIV-1 infection: impact of a therapeutic vaccination strategy combined with interleukin (IL)-2 compared with IL-2 alone in the ANRS 095 Randomized Study.

HIV-specific T cell responses play a critical role in the control of infection. We evaluated the impact of immune-based interventions in patients first treated during primary HIV-1 infection (PHI). Forty-three patients were randomized within three groups, to receive either interleukin-2 (IL-2 group), or boosts of ALVAC-HIV (vCP1433) and LIPO-6T followed by interleukin-2 (Vac-IL2 group), compared with no immune intervention (control group), and were monitored for T cell responses.

Clinical safety of HIV lipopeptides used as vaccines in healthy volunteers and HIV-infected adults.

Background: HIV-1 lipopeptides have been developed by the French National Agency for AIDS Research (ANRS) for use as candidate vaccine against HIV since 1994. Between 1996 and 2005, four different lipopeptide constructs were tested alone or in combination with recombinant canarypox HIV vaccines in 10 trials conducted in France. The aim of this study was to review clinical safety of HIV lipopeptides.

Sustained control of viremia following therapeutic immunization in chronically HIV-1-infected individuals.

Objective: Viral rebounds inevitably follow interruption of antiretroviral treatment in HIV-1-infected individuals. The randomized ANRS 093 aimed at investigating whether a therapeutic immunization was effective in containing the long-term viral replication following discontinuation of antiretroviral drugs in patients.

Methods: Seventy HIV-1-infected patients effectively treated with antiretroviral drugs were randomized to continue treatment alone or in combination with four boosts of ALVAC 1433 and HIV-LIPO-6T vaccines followed by three cycles of subcutaneous interleukin-2.

Experience using MedDRA for global events coding in HIV clinical trials.

Objectives: To assess the feasibility of coding with MedDRA, the Medical Dictionary for Regulatory Activities, not only serious adverse events required for notification but also all other events usually reported in HIV clinical trials. To develop an approach for MedDRA implementation within an institutional research unit that contributes to an efficient, concise and reproducible event coding. To evaluate the impact of the maintenance and the versioning of this new medical terminology.

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.

Immunological and virological efficacy of a therapeutic immunization combined with interleukin-2 in chronically HIV-1 infected patients.

Objective: Several lines of evidence suggest that the immune system may control HIV-1 replication, but that it could fail in the long term. Strategies aimed to elicit specific immune responses may enable patients to contain virus replication.

Methods: HIV-1-infected patients were randomized to continue either their antiviral therapy alone (controls; n = 37) or with four boosts of vaccination combining ALVAC-HIV (vCP1433) and Lipo-6T vaccines (weeks 0, 4, 8, 12) followed by three cycles of subcutaneous interleukin-2 (weeks 16, 24, 32) (Vac-IL-2 group; n = 34).

A survival method to estimate the time to occurrence of mutations: an application to thymidine analogue mutations in HIV-1-infected patients.

Virologic studies of human immunodeficiency virus type 1-infected patients have investigated either the emergence of resistance mutations according to the treatment received (type I) or their effect on subsequent regimens (type II). Type I studies provide an estimation of the frequency distribution of mutations for a given duration of therapy, but the delay to emergence of these mutations cannot be assessed. We suggest using a nonparametric estimator that generalizes the Kaplan-Meier method to data from type II studies to estimate the time to occurrence of mutations.

Predictive factors and selection of thymidine analogue mutations by nucleoside reverse transcriptase inhibitors according to initial regimen received.

Thymidine analogue mutations were determined and compared in patients who received zidovudine monotherapy and added didanosine or zalcitabine, and in patients who started with one of these dual nucleoside combinations. Although patients who started in the era of zidovudine monotherapy had a longer duration of therapy compared with the other group, there was no statistical difference in the number of mutations between the two groups. However, thymidine analogue mutations were more frequent in patients who added didanosine to zidovudine monotherapy compared with those who added zalcitabine.

Effect of zidovudine resistance mutations on virologic response to treatment with zidovudine or stavudine, each in combination with lamivudine and indinavir.

The authors studied the effect of zidovudine (ZDV) resistance mutation on virologic response to treatment with ZDV or stavudine (d4T) each in combination with lamivudine and indinavir. Viral genotyping was performed on plasma HIV-1 RNA at study entry and concerned 155 patients previously treated with ZDV, didanosine, or zalcitabine and enrolled in the NOVAVIR (Agence National de Recherche sur le SIDA [ANRS] 073) trial. Three virologic responses were investigated: early response (<50 copies/mL at week 24), late response (<500 copies/mL at week 80), and virologic failure (two HIV-1 RNA >5000 copies/mL).

Increased risk of lipoatrophy under stavudine in HIV-1-infected patients: results of a substudy from a comparative trial.

Objectives: To compare the incidence of clinical lipodystrophy in HIV-1-infected patients receiving zidovudine or stavudine, in combination with indinavir and lamivudine, in a randomized trial.

Methods: NOVAVIR was a randomized multicentre trial comparing stavudine/lamivudine/indinavir and zidovudine/lamivudine/indinavir in 170 patients pretreated with zidovudine, didanosine or zalcitabine (> 6 months), but naive for lamivudine, stavudine and protease inhibitors. The incidence of clinical lipodystrophy and metabolic abnormalities was assessed in a subgroup of 101 patients after 30 months of follow-up.

Adherence to antiretroviral therapy and outcomes in HIV-infected patients enrolled in an induction/maintenance randomized trial.

Objective: To examine the effect of adherence to therapy on early virological response, later virological failure, and occurrence of adverse events in HIV-infected patients.

Design: A randomized trial of 3-month induction period of zidovudine/lamivudine/indinavir followed by a maintenance phase of zidovudine/lamivudine/indinavir, zidovudine/lamivudine or zidovudine/indinavir.

Main Outcomes: Adherence was assessed by pill count.

Final analysis of the Trilège induction-maintenance trial: results at 18 months.

Background: First results of Trilège demonstrated that the strategy of less intensive antiviral therapy is less effective than continuation of triple-drug therapy.

Objective: To compare the final number of failures at month 18 and to study viral dynamics in patients experiencing a virological failure.

Design: Longitudinal follow-up from a randomized controlled trial.