Unravelling the dynamics of selection of multiresistant variants to integrase inhibitors in an HIV-1-infected child using ultra-deep sequencing.

Background: Ultra-deep sequencing (UDS) allows detection of minority resistant variants (MRVs) with a threshold of 1% and could be useful to identify variants harbouring single or multiple drug-resistance mutations (DRMs).

Objectives: We analysed the integrase gene region longitudinally using UDS in an HIV-1-infected child rapidly failing a raltegravir-based regimen.

Methods: Longitudinal plasma samples at baseline and weeks 4, 8, 13, 17 and 39 were obtained, as well as the mother's baseline plasma sample.

Multi-site clinical evaluation of the Xpert(®) HIV-1 viral load assay.

Background: The most important reason for measuring HIV-1 viral load (VL) is to monitor the effectiveness of antiretroviral therapy (ART), both for the initial therapeutic response and sustained responses. Maintaining low or undetectable HIV-1 VL levels can reduce both the risks of progression to AIDS and transmission of infection to others.

Objectives: To evaluate the diagnostic accuracy of Xpert(®) HIV-1 Viral Load (VL) assay compared to the Abbott RealTime HIV-1 assay, including assessing specificity by testing plasma specimens from confirmed HIV-1 negative blood donors.

Performance Evaluation of the New HIV-1 Quantification Assay, Xpert HIV-1 Viral Load, on a Wide Panel of HIV-1 Variants.

Objective: To evaluate the quantification performance of the new Cepheid GeneXpert HIV-1 viral load assay, on a wide panel of HIV-1 variants.

Methods: Clinical performance was evaluated relative to the Abbott RealTime HIV-1 assay on 285 HIV-1 seropositive samples selected to cover the assays quantification range (40 copies/mL-10,000,000 copies/mL), and included RNA undetectable or detected seropositive samples. The panel comprised 120 subtype B, 150 non-B, and 15 nontypable clinical samples; serial dilutions of 18 viral supernatants representative of the divergent viruses of HIV-1 groups N, O, and P were also tested.

A Multiplex PCR Approach for Detecting Dual Infections and Recombinants Involving Major HIV Variants.

The cocirculation of different HIV types and groups can lead to dual infections and recombinants, which hinder diagnosis and therapeutic management. We designed two multiplex PCRs (mPCRs) coupled with capillary electrophoresis to facilitate the detection of such infections. The first, MMO2, targets three variants (HIV-1/M, HIV-1/O, and HIV-2), and the second, MMO, targets HIV-1/M and HIV-1/O.

Hepatitis C virus and HIV seroprevalences, sociodemographic characteristics, behaviors and access to syringes among drug users, a comparison of geographical areas in France, ANRS-Coquelicot 2011 survey.

Background: People who use drugs (PWUDs) are at a high risk for hepatitis C virus (HCV) and human immunodeficiency virus (HIV), but they have different characteristics depending on the local context. In France, seroprevalence, sociodemographic, and behavior information have only been studied at a national level rather than at a local level. The aim of this study was to describe and examine profile and drug use practice differences in seven French cities and departments and to assess whether these differences can explain HCV and HIV seroprevalence variations between French geographical areas.

Broad Range of Hepatitis B Virus (HBV) Patterns, Dual Circulation of Quasi-Subgenotype A3 and HBV/E and Heterogeneous HBV Mutations in HIV-Positive Patients in Gabon.

Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010-2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification.

First evidence of transmission of an HIV-1 M/O intergroup recombinant virus.

Objective: Despite the genetic divergence between HIV-1 groups M and O, HIV-1  M/O intergroup recombinants were reported. Actually, there is no data on the transmissibility of such recombinant forms. During a surveillance of HIV genetic diversity in Cameroon, we investigated the possible direct transmission of an HIV-1  M/O recombinant virus in an HIV-infected couple.

V1/V2 Neutralizing Epitope is Conserved in Divergent Non-M Groups of HIV-1.

Background: Highly potent broadly neutralizing monoclonal antibodies (bNAbs) have been obtained from individuals infected by HIV-1 group M variants. We analyzed the cross-group neutralization potency of these bNAbs toward non-M primary isolates (PI).

Material And Methods: The sensitivity to neutralization was analyzed in a neutralization assay using TZM-bl cells.

Comparison of the bioMérieux NucliSENS EasyQ HIV-1 v2.0-HIV-1 RNA quantification assay versus Abbott RealTime HIV-1 and Roche Cobas TaqMan HIV-1 v2.0 on current epidemic HIV-1 variants.

Background: An improved version of the bioMérieux NucliSENS(®) EasyQ(®) HIV-1 v2.0 has been introduced to overcome the underquantification observed with previous versions, especially with non-B HIV-1 subtypes.

Objectives: Comparing bioMérieux NucliSENS(®) EasyQ(®) HIV-1 v2.

Combining the Estimated Date of HIV Infection with a Phylogenetic Cluster Study to Better Understand HIV Spread: Application in a Paris Neighbourhood.

Objectives: To relate socio-demographic and virological information to phylogenetic clustering in HIV infected patients in a limited geographical area and to evaluate the role of recently infected individuals in the spread of HIV.

Methods: HIV-1 pol sequences from newly diagnosed and treatment-naive patients receiving follow-up between 2008 and 2011 by physicians belonging to a health network in Paris were used to build a phylogenetic tree using neighbour-joining analysis. Time since infection was estimated by immunoassay to define recently infected patients (very early infected presenters, VEP).

The Two-Phase Emergence of Non Pandemic HIV-1 Group O in Cameroon.

Unlike the pandemic form of HIV-1 (group M), group O viruses are endemic in west central Africa, especially in Cameroon. However, little is known about group O's genetic evolution, and why this highly divergent lineage has not become pandemic. Using a unique and large set of group O sequences from samples collected from 1987 to 2012, we find that this lineage has evolved in successive slow and fast phases of diversification, with a most recent common ancestor estimated to have existed around 1930 (1914-1944).

Plasma HIV-2 RNA According to CD4 Count Strata among HIV-2-Infected Adults in the IeDEA West Africa Collaboration.

Background: Plasma HIV-1 RNA monitoring is one of the standard tests for the management of HIV-1 infection. While HIV-1 RNA can be quantified using several commercial tests, no test has been commercialized for HIV-2 RNA quantification. We studied the relationship between plasma HIV-2 viral load (VL) and CD4 count in West African patients who were either receiving antiretroviral therapy (ART) or treatment-naïve.

Performance of rapid tests for discrimination between HIV-1 and/or HIV-2 infections.

Major differences exist between HIV-1 and HIV-2 in terms of epidemiology, pathogenicity, sensitivity to antiretrovirals. Determining the type of HIV infecting a patient is essential for management. The aim of this study was to evaluate the ability of simple/rapid tests to differentiate between HIV-1 and/or HIV-2 infections.

HIV-1 Group O Resistance Against Integrase Inhibitors.

Background: HIV-1 group O (HIV-O) is a rare variant that is characterized by a high number of natural polymorphisms in the integrase coding region that may impact on susceptibility to integrase strand transfer inhibitors (INSTIs) and on the emergence of resistance substitutions. We previously reported that HIV-O is more susceptible to RAL than HIV-1 group M (HIV-M).

Methods: The aim of this study was to assess pathways of resistance to INSTIs in group 0 variants.

HIV-1 subtype B-infected MSM may have driven the spread of transmitted resistant strains in France in 2007-12: impact on susceptibility to first-line strategies.

Background: Our study describes the prevalence of transmitted drug resistance (TDR) among 1318 French patients diagnosed at the time of primary HIV-1 infection (PHI) in 2007-12.

Methods: HIV-1 resistance-associated mutations (RAMs) were characterized using both the 2009 WHO list of mutations and the French ANRS algorithm. A genotypic susceptibility score was estimated for each first-line recommended ART combination.

Differential regulation of NF-κB-mediated proviral and antiviral host gene expression by primate lentiviral Nef and Vpu proteins.

NF-κB is essential for effective transcription of primate lentiviral genomes and also activates antiviral host genes. Here, we show that the early protein Nef of most primate lentiviruses enhances NF-κB activation. In contrast, the late protein Vpu of HIV-1 and its simian precursors inhibits activation of NF-κB, even in the presence of Nef.

Characteristics of patients recently infected with HIV-1 non-B subtypes in France: a nested study within the mandatory notification system for new HIV diagnoses.

The presence of HIV-1 non-B subtypes in Western Europe is commonly attributed to migration of individuals from non-European countries, but the possible role of domestic infections with non-B subtypes is not well investigated. The French mandatory anonymous reporting system for HIV is linked to a virological surveillance using assays for recent infection (<6 months) and serotyping. During the first semester of years 2007 to 2010, any sample corresponding to a non-B recent infection was analyzed by sequencing a 415-bp env region, followed by phylogenetic analysis and search for transmission clusters.

Drift of the HIV-1 envelope glycoprotein gp120 toward increased neutralization resistance over the course of the epidemic: a comprehensive study using the most potent and broadly neutralizing monoclonal antibodies.

Extending our previous analyses to the most recently described monoclonal broadly neutralizing antibodies (bNAbs), we confirmed a drift of HIV-1 clade B variants over 2 decades toward higher resistance to bNAbs targeting almost all the identified gp120-neutralizing epitopes. In contrast, the sensitivity to bNAbs targeting the gp41 membrane-proximal external region remained stable, suggesting a selective pressure on gp120 preferentially. Despite this evolution, selected combinations of bNAbs remain capable of neutralizing efficiently most of the circulating variants.

HIV-1 group O integrase displays lower enzymatic efficiency and higher susceptibility to raltegravir than HIV-1 group M subtype B integrase.

HIV-1 group O (HIV-O) is a rare HIV-1 variant characterized by a high number of polymorphisms, especially in the integrase coding region. As HIV-O integrase enzymes have not previously been studied, our aim was to assess the impact of HIV-O integrase polymorphisms on enzyme function and susceptibility to integrase inhibitors. Accordingly, we cloned and purified integrase proteins from each of HIV-1 group O clades A and B, an HIV-O divergent strain, and HIV-1 group M (HIV-M, subtype B), used as a reference.

Performance of the Liaison XL Murex HIV Ab/Ag test on clinical samples representing current epidemic HIV variants.

Screening for HIV infection has improved since the first immunoassays. Today, diagnosis of HIV infection can be performed with fourth-generation tests that track both the patient's antibodies and HIV antigen. The objective of this study was to evaluate the clinical sensitivity and specificity of the new DiaSorin Liaison XL Murex HIV Ab/Ag assay compared to another fourth-generation assay, the Abbott Architect HIV Ag/Ab Combo kit.