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Objectives Presence of baseline hepatitis C virus (HCV) resistance-associated substitutions (RASs) can impair treatment outcome of direct-acting antivirals. We investigated the prevalence of pre-treatment HCV resistance among recently HCV-infected men who have sex with men (MSM) with high risk behaviours, either human immunodeficiency virus (HIV) co-infected or at high risk of HIV acquisition and under pre-exposure prophylaxis (PrEP). Methods NS5A and NS3 fragments were deep sequenced on pre-treatment samples of 72 subjects using Illumina MiSeq paired-end sequencing technology. Ultra-deep sequencing data were analysed by SmartGene® platform. RASs mentioned in the literature were analysed and interpreted depending on genotype (GT) at 10% cut-off. Results HCV genotyping showed 36 (50.0%) GT1a, 31 (43.1%) GT4d and 5 (6.9%) GT3a infections. Fifty-five patients (76.4%) were co-infected with HIV and 15 (20.8%) received PrEP. In GT1a viruses, NS3 RASs were found in 4/30 viruses (13.3%; S122 G/N, R155 K and I170 V) and Q80 K polymorphism was present in 14/30 viruses (46.7%). No NS3 RASs were detected in GT4d and GT3a viruses. NS5A RASs were detected in 3/36 GT1a viruses (8.3%; Q30E/R, L31 M and H58 L). NS5A subtype-specific polymorphisms L30R and T58 P were found at high frequencies in 31/31 (100%) and 16/31 (51.6%) GT4d viruses, respectively. One RAS M31 L was also observed along with the polymorphisms L30R and T58 P. No NS5A RASs were detected in GT3a viruses. Conclusion A low level of RASs to NS3 and NS5A inhibitors in pre-treatment samples was detected in the study population. Our findings reassure the clinical management of HCV infection in this high-risk population.

Background HIV, HBV and HCV infections continue to represent major health concerns, especially among key at-risk populations such as men who have sex with men (MSM), people who inject drugs (PWIDs), transgender women (TGW) and sex workers (SW). The objective of the ANRS-CUBE study was to evaluate the acceptability of a healthcare, community-based strategy offering a triple rapid HIV-HBV-HCV testing, and HBV vaccination, targeted at three priority groups (MSM, PWIDs and TGW/SWs), in three community centers, in the Paris area. Methods This longitudinal multicentric non-randomized study included all adult volunteers attending one of the three specialized community centers in Paris, between July 2014 and December 2015. HIV, HBV and HCV status and acceptability of HBV vaccination were evaluated. Results A total of 3662, MSM, 80 PWIDs and 72 TGW/SW were recruited in the three centers respectively. Acceptability of rapid tests was 98.5% in MSM and 14.9% in TGW/SWs, but could not be estimated in PWIDs since the number of users attending and the number of proposals were not recorded. User acceptability of HBV vaccination was weak, only 17.9% of the eligible MSM (neither vaccinated, nor infected) agreed to receive the first dose, 12.2% two doses, 5.9% had a complete vaccination. User acceptability of HBV vaccination was greater in PWIDs and TGW/SWs, but decreased for the last doses (66.7 and 53.3% respectively received a first dose, 24.4 and 26.7% a second dose and 6.7 and 0% a third dose). Fifty-three participants (49 MSM and 4 PWIDs) were discovered HIV positive, more than half with a recent infection. All but two HIV positive participants were linked to appropriate care in less than one month. Conclusions Rapid HIV-HCV-HBV screening showed a very high level of acceptability among MSM. Efforts need to be made to improve immediate acceptability for HBV vaccination, especially among MSM, and follow-up doses compliance. Our results show the important role of community centers in reaching targets, often fragile, populations, while also suggesting the need to reinforce on-site human support in terms of testing and vaccination, especially when addressing PWIDs.

International audience; Background - Increasing incidence of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-positive men having sex with men (MSM) has been described in recent years. Phylogenetic analyses of acute HCV infections were undertaken to characterize the dynamics during the epidemic in Paris, and associated sexually transmitted infections (STIs) were evaluated. Methods - Sanger sequencing of polymerase gene was performed. Maximum likelihood phylogenies were reconstructed using FastTree 2.1 under a GTR+CAT model. Transmission chains were defined as clades with a branch probability ≥0.80 and intraclade genetic distances

International audience; INTRODUCTION: Mixed hepatitis C virus (HCV) genotype (GT) infections are clinically important as different genotypes have varied sensitivities to direct-acting antivirals (DAAs). A high prevalence of mixed GT infections was observed in individuals who inject drugs and had multiple HCV exposures. The prevalence of mixed HCV GT infections in men who have sex with men (MSM) and high-risk behaviors was investigated by ultra-deep sequencing (UDS).METHODS: NS5B fragment was sequenced from viruses of patients with recent HCV infection: there were 50 HIV-positive and 18 HIV-negative patients, including 13 from the ANRS Pre-Exposure Prophylaxis (PrEP) IPERGAY study. UDS data were analysed using Geneious (version 10.3.2). Phylogenetic trees were constructed using FastTree (version 2.1).RESULTS: HCV sequencing showed GT1a (47.1%), GT4d (41.2%), GT3a (8.8%) and GT2k (2.9%). We detected three (4.4%) mixed GT infections: one between predominant GT4d and minority GT1a, one between predominant GT4d and minority GT1b, and one between predominant GT1a and minority GT4d virus. The rates of minority GT viral populations detected in viruses of the three patients with mixed GT infections were 0.32%, 10.7%, and 1.3%, respectively. The first two patients were HIV co-infected and the third was HIV-negative under PrEP. The anti-HCV treatment was successful in all three patients.CONCLUSION: This work showed uncommon mixed HCV GT infections in MSM at high risk of multiple HCV exposures. The impact of these infections on treatment response has not been established but further studies on more patients are necessary. To prevent treatment failure in this population, regular monitoring of treatment response is needed, particularly when pan-genotypic treatment is not used.

Nonorgan-specific autoantibodies (AAbs) are used for diagnosing autoimmune diseases but can also be detected in other conditions. We carried out a cross-sectional study with the aim to screen HIV1-infected patients in the era of highly active antiretroviral therapy (HAART) for AAbs and to analyze the association of their presence with hypergammaglobulinemia and immunovirological status. Blood samples from HIV1-infected patients without major concomitant illnesses followed in 2 hospitals in Paris, France were tested for immunovirological status, serum immunoglobulin G (IgG) level, antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), anti-extractable nuclear antigens (anti-ENAs), anticardiolipin (aCL), anti-β2glycoprotein1 (anti-β2GP1), and antineutrophil cytoplasmic antibodies (ANCAs). Clinically relevant AAbs were defined as ANAs with titers ≥1:160, anti-dsDNA or anti-ENA antibodies; aCL or anti-β2GP1 antibodies with a level ≥40 U/ml; and ANCAs reacting with proteinase 3 or myeloperoxidase. We included 92 patients (mean age 47 years, men 55%, sub-Saharan African background 55%, HAART 85%, mean CD4 lymphocyte count 611/mm3, viral load

The dose-response relationship for radiation-induced leukemia was examined in a pooled analysis of three exposed populations: Japanese atomic bomb survivors, women treated for cervical cancer, and patients irradiated for ankylosing spondylitis. A total of 383 leukemias were observed among 283,139 study subjects. Considering all leukemias apart from chronic lymphocytic leukemia, the optimal relative risk model had a dose response with a purely quadratic term representing induction and an exponential term consistent with cell sterilization at high doses; the addition of a linear induction term did not improve the fit of the model. The relative risk decreased with increasing time since exposure and increasing attained age, and there were significant (P < 0.00001) differences in the parameters of the model between datasets. These differences were related in part to the significant differences (P = 0.003) between the models fitted to the three main radiogenic leukemia subtypes (acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia). When the three datasets were considered together but the analysis was repeated separately for the three leukemia subtypes, for each subtype the optimal model included quadratic and exponential terms in dose. For acute myeloid leukemia and chronic myeloid leukemia, there were reductions of relative risk with increasing time after exposure, whereas for acute lymphocytic leukemia the relative risk decreased with increasing attained age. For each leukemia subtype considered separately, there was no indication of a difference between the studies in the relative risk and its distribution as a function of dose, age and time (P > 0.10 for all three subtypes). The nonsignificant indications of differences between the three datasets when leukemia subtypes were considered separately may be explained by random variation, although a contribution from differences in exposure dose-rate regimens, inhomogeneous dose distribution within the bone marrow, inadequate adjustment for cell sterilization effects, or errors in dosimetry could have played a role.

Since the early 1980s, mass spectrometry has emerged as a particularly powerful tool for analysis and characterization of proteins in research. Recently, bacteriologists have focused their attention on the use of mass spectrometry (MS) for bacterial identification, especially Matrix Assisted Laser Desorption Ionization Time-Of-Flight (MALDI-TOF). Moreover, recent publications have evaluated MALDI-TOF in microbiology laboratory for routine use. MALDI-TOF-MS is a rapid, precise, and cost-effective method for identification of intact bacteria, compared to conventional phenotypic techniques or molecular biology. Furthermore, it allows identification of bacteria directly from clinical samples (blood cultures for example). The goal of this review was to update recent data concerning routine identification of microorganisms by MALDI-TOF in the clinical microbiology laboratory.

Introduction: Herpes Simplex Virus-2 (HSV-2) is known to be a potent co-factor of Human Immunodeficiency type 1 virus (HIV-1) heterosexual transmission. We were interested in assessing the distribution of HIV-1 and HSV-2 epidemics at the national level in Chad. Methodology: In 2007, a population-based anonymous serosurvey for HIV-1 and HSV-2 infections, using dried blood spots, was conducted. The study included 548 adults living in 15 regions of Chad. After specimen elution, serological testing for HIV and HSV-2 infections was performed. Results: Countrywide, the HIV-1 and HSV-2 seroprevalences were 11.1% and 15.7%, respectively. A positive correlation was observed with the highest HIV-1 prevalence seen in regions of the highest HSV-2 prevalence, especially in two conflict-affected eastern provinces of Darfur. Conclusion: Urgent public health interventions are needed in regions of Chad where high HSV-2 prevalence may be increasing the risk of HIV propagation.

The usefulness of a point-of-care immunochromatographic dual test for the simultaneous detection of both nontreponemal and Treponema pallidum-specific antibodies (Chembio Diagnostics Systems Inc., Medford, NY, USA) was assessed in various situations related to syphilis, by reference to conventional syphilis serology. Thawed sera were obtained from 100 adults including 36 primary syphilis, 6 secondary syphilis, 6 re-infection, 9 recently-treated syphilis, and 43 old syphilis. Doubtful reactivities for the treponemal line were considered positive; doubtful reactivities for the nontreponemal line were considered positive only when the treponemal line was present. The sensitivity, the specificity, and its concordance to gold standard serology of treponemal line were high, around 90%. The sensitivity of nontreponemal line was 96.3%, its specificity 76.7%, and its concordance 83.4%. In conclusion, the dual rapid test from Chembio Diagnostics Systems Inc. is useful for rapid point-of-care diagnosis in the various situations encountered with patients suffering from syphilis.