Long-term efficacy of darunavir/ritonavir monotherapy in patients with HIV-1 viral suppression: week 96 results from the MONOI ANRS 136 study.

Objectives: Long-term results at week 96 are needed to evaluate the capacity of the darunavir/ritonavir monotherapy strategy to maintain a sustained control of the HIV-1 viral load.

Methods: MONOI is a prospective, open-label, non-inferiority, randomized, 96 week trial comparing darunavir/ritonavir monotherapy versus a darunavir/ritonavir triple-therapy strategy to maintain HIV-1 viral load suppression in HIV-1-infected patients.

Clinical Trial Registration: NCT00412551.

E17A mutation in HIV-1 Vpr confers resistance to didanosine in association with thymidine analog mutations.

Background: HIV-1 accessory Vpr protein is involved in the reverse transcription process and has been shown to modulate the virus mutation rate. This process may play a role in the kinetics of appearance of drug resistance mutations under antiretroviral treatment.

Methods: Vpr sequences were analyzed from plasma viruses derived from 97 HIV-1-infected individuals failing antiretroviral treatment and 63 antiretroviral-naïve patients.

Ten-year diabetes incidence in 1046 HIV-infected patients started on a combination antiretroviral treatment.

Objective: To evaluate the incidence and determinants of diabetes in a cohort of HIV-infected adults initiated with combination antiretroviral treatment (cART) in 1997-1999 and followed up to 2009.

Design: Prospective study of 1046 patients at 47 French clinical sites.

Methods: Potential determinants of diabetes occurrence, defined by confirmed increased glycemia and/or initiation of antidiabetic treatment, were assessed by a proportional hazards model, including time-updated metabolic parameters and ART exposure.

Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial.

Background: Twice-daily raltegravir with once-daily tenofovir-emtricitabine is an effective initial antiretroviral regimen for patients with HIV-1. On the basis of pharmacokinetic data suggesting efficacy of once-daily raltegravir and because adherence is often improved with once-daily dosing, we aimed to compare these dosing schedules.

Methods: In our international, double-blind, randomised, phase 3 non-inferiority study, we enrolled antiretroviral-naive patients with HIV RNA loads of more than 5000 copies per mL and no baseline resistance to tenofovir or emtricitabine at 83 centres worldwide.

Factors associated with virological failure in HIV-1-infected patients receiving darunavir/ritonavir monotherapy.

Background: Our objective was to determine virological and clinical characteristics associated with virological failure in human immunodeficiency virus (HIV)-infected patients switching to darunavir/ritonavir (DRV/r) monotherapy.

Methods: The main outcome was virologic rebound, defined as 2 consecutive measurements of HIV-1 plasma RNA viral load (VL) >50 copies/mL. A logistic model was used to investigate which variables were predictive of a virologic rebound at weeks 48 (W48) and 96 (W96).

Randomized comparison of metabolic and renal effects of saquinavir/r or atazanavir/r plus tenofovir/emtricitabine in treatment-naïve HIV-1-infected patients.

Objectives: The aim of the study was to compare the effects on lipids, body composition and renal function of once-daily ritonavir-boosted saquinavir (SQV/r) or atazanavir (ATV/r) in combination with tenofovir/emtricitabine (TDF/FTC) over 48 weeks.

Methods: An investigator-initiated, randomized, open-label, multinational trial comparing SQV/r 2000/100 mg and ATV/r 300/100 mg once daily, both in combination with TDF/FTC, in 123 treatment-naïve HIV-1-infected adults was carried out. The primary endpoint was to demonstrate noninferiority of SQV/r compared with ATV/r with respect to the change in fasting cholesterol after 24 weeks.

Influence of interferon-based therapy on liver fibrosis progression in HIV/HCV coinfected patients: a retrospective repeated liver biopsy analysis.

Background & Aims: Hepatitis C virus (HCV) coinfection is one of the leading causes of mortality in human immunodeficiency virus-infected patients. The current standard of care leads to cure only in a part of these patients. The course of the disease is determined by the rapidity of liver fibrosis progression (LFP).

Atazanavir/ritonavir-based combination antiretroviral therapy for treatment of HIV-1 infection in adults.

In the past 15 years, improvements in the management of HIV infection have dramatically reduced morbidity and mortality. Similarly, rapid advances in antiretroviral medications have resulted in the possibility of life-long therapy with simple and tolerable regimens. Protease inhibitors have been important medications in regimens of combination antiretroviral therapy for the treatment of HIV.

Comparative effectiveness of continuing a virologically effective first-line boosted protease inhibitor combination or of switching to a three-drug regimen containing either efavirenz, nevirapine or abacavir.

Objectives: To compare virological effectiveness in patients who continued on a virologically successful first-line boosted protease inhibitor (PI)-containing combination antiretroviral therapy (cART) regimen or who switched to a PI-free cART including efavirenz, nevirapine or abacavir.

Methods: From the French Hospital Database on HIV, we selected 439 patients with undetectable viral load (VL) on a first-line boosted PI-containing cART regimen who switched to a PI-free combination including efavirenz, nevirapine or abacavir. Each of these patients was matched with three patients who continued to take their first-line cART regimen, on the basis of gender, age, CD4 cell count, VL, date of cART initiation and the duration of VL undetectability.

CTL escape mediated by proteasomal destruction of an HIV-1 cryptic epitope.

Cytotoxic CD8+ T cells (CTLs) play a critical role in controlling viral infections. HIV-infected individuals develop CTL responses against epitopes derived from viral proteins, but also against cryptic epitopes encoded by viral alternative reading frames (ARF). We studied here the mechanisms of HIV-1 escape from CTLs targeting one such cryptic epitope, Q9VF, encoded by an HIVgag ARF and presented by HLA-B*07.

Risk factors of chronic kidney disease in HIV-infected patients.

Background And Objectives: The main aim of this study was determining the risk factors of chronic kidney disease (CKD) in HIV-1-infected patients.

Design, Setting, Participants, & Measurements: Patients were followed from seven large HIV reference centers in France that maintain prospective databases on HIV-1-infected patients. The main outcome was the time to CKD defined as two consecutive measures of estimated GFR ≤60 ml/min per 1.

High prevalence of antiretroviral drug resistance among HIV-1-untreated patients in Guinea-Conakry and in Niger.

Background: The aim of the study was to assess the prevalence of antiretroviral drug resistance mutations in HIV-1 from recently diagnosed and untreated patients living in Conakry, Guinea-Conakry and in Niamey, Niger.

Methods: The study was performed in two countries of Western Africa - Guinea-Conakry and Niger - using the same survey method in both sites. All newly HIV-1 diagnosed patients, naive of antiretroviral drugs, were consecutively included during September 2009 in each of the two sites.

Upgraded Cobas Ampliprep-Cobas TaqMan version 2.0 HIV-1 RNA quantification assay versus first version: correction of underestimations.

The large underestimations of HIV RNA quantification observed in 17 patients with the first version of Cobas TaqMan assay have been successfully corrected in the upgraded version 2.0. In comparison with the Abbott RealTime assay, the mean difference that was 1.

Prevalence of resistance mutations related to integrase inhibitor S/GSK1349572 in HIV-1 subtype B raltegravir-naive and -treated patients.

Objectives: To compare the frequency of previously in vitro-selected integrase mutations (T124A, T124A/S153F, S153Y, T124A/S153Y and L101I/T124A/S153Y) conferring resistance to S/GSK1349572 between HIV-1 subtype B integrase inhibitor (INI)-naive and raltegravir-treated patients.

Methods: Integrase sequences from 650 INI-naive patients and 84 raltegravir-treated patients were analysed.

Results: The T124A mutation alone and the combination T124A/L101I were more frequent in raltegravir-failing patients than in INI-naive patients (39.

Six-year follow-up of hepatitis B surface antigen concentrations in tenofovir disoproxil fumarate treated HIV-HBV-coinfected patients.

Background: Quantitative measurement of hepatitis B surface antigen (HBsAg) has been proposed as a surrogate marker of treatment efficacy when HBV DNA load becomes undetectable. Our main objective was to study the kinetics of HBsAg level in HIV-HBV-coinfected patients with undetectable HBV DNA load under treatment containing tenofovir disoproxil fumarate (TDF).

Methods: A retrospective analysis was performed on frozen serum samples of 33 HIV-HBV-coinfected patients who were treated with TDF and had undetectable HBV DNA for ≥1 year.

Raltegravir concentrations in the genital tract of HIV-1-infected women treated with a raltegravir-containing regimen (DIVA 01 study).

We studied the penetration of raltegravir and HIV shedding in the genital tract among 14 HIV-1-infected women receiving a raltegravir-containing regimen who had <40 copies/ml blood plasma (BP) HIV RNA. None of the cervicovaginal fluid (CVF) samples showed detectable HIV RNA. Median raltegravir concentrations were 235 ng/ml in BP and 93 ng/ml in CVF, with a CVF/BP ratio of approximately 2.

HIV disease progression despite suppression of viral replication is associated with exhaustion of lymphopoiesis.

The mechanisms of CD4(+) T-cell count decline, the hallmark of HIV disease progression, and its relationship to elevated levels of immune activation are not fully understood. Massive depletion of CD4(+) T cells occurs during the course of HIV-1 infection, so that maintenance of adequate CD4(+) T-cell levels probably depends primarily on the capacity to renew depleted lymphocytes, that is, the lymphopoiesis. We performed here a comprehensive study of quantitative and qualitative attributes of CD34(+) hematopoietic progenitor cells directly from the blood of a large set of HIV-infected persons compared with uninfected donors, in particular the elderly.

Old age and anti-cytomegalovirus immunity are associated with altered T-cell reconstitution in HIV-1-infected patients.

Objective And Design: Increasing evidence supports a parallel between HIV-1 infection and immune aging, which is particularly apparent with common changes in naive versus memory T-cell proportions. Here, we aimed at refining the value of common T-cell-associated markers of immunosenescence during HIV disease progression or aging, and at exploring further the impact in this context of old age as well as cytomegalovirus (CMV) co-infection, which is predominant in HIV-1-infected individuals.

Methods: Frequencies of naive or CD57(+) memory T cells as well as the magnitude of CMV-pp65 T cells were measured in HIV-1-infected patients grouped according to disease progression status, treatment and age.

Historical HIV-RNA resistance test results are more informative than proviral DNA genotyping in cases of suppressed or residual viraemia.

Background: Resistance genotyping is often requested due to residual HIV viraemia or for treatment optimization, but may be unsuccessful if plasma RNA levels are too low or undetectable. Analyses of proviral HIV-DNA can provide information about the viral reservoir, because integrated DNA reflects both actively and latently infected cells.

Objectives: To determine whether proviral DNA is a potential relevant alternative to HIV-RNA for resistance genotyping in this context.

Positive impact of HIV-1 gag cleavage site mutations on the virological response to darunavir boosted with ritonavir.

We assessed the roles of baseline gag and gag-pol cleavage site mutations (CSM) on the virological outcome of a darunavir-based regimen in highly antiretroviral-experienced patients. We showed the association, in multivariate analysis, between the A431V gag CSM and the virological response, defined as a reduction in plasma HIV-1 RNA to <50 copies/ml at month 3 (P = 0.028).

HIV genetic diversity between plasma and cerebrospinal fluid in patients with HIV encephalitis.

In patients with HIV encephalitis, a low viral diversity between the plasma and cerebrospinal fluid (CSF) HIV-1 viruses was associated with detectable HIV RNA in plasma and a higher level of central nervous system penetration effectiveness (CPE) score, taking into account the genotypic susceptibility score of the current treatment (named balanced score). This result suggests that the CSF viruses were probably originating from the plasma. Conversely, a high viral genetic diversity was associated with an undetectable HIV RNA in plasma and low-balanced CPE, which is in favour of an autonomous replication in the central nervous system.

The spectrum of malignancies in HIV-infected patients in 2006 in France: the ONCOVIH study.

Since no large descriptive studies of incident cancers in HIV-infected patients are available in France, the nationwide cross-sectional ONCOVIH study aimed to prospectively report new malignancies diagnosed in HIV-infected patients in cancer centers and HIV/AIDS centers. We estimated the number of cancers in France for the year 2006 using the capture-recapture methods with two sources: ONCOVIH and the FHDH ANRS-CO4 cohort, as well as the completeness of the sources. Incidence and relative risks (RR) to the general population were estimated.