High clustering of acute HCV infections and high rate of associated STIs among Parisian HIV-positive male patients.

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 <0.02 nucleotide substitutions per sites. STIs detected ≤1 month before HCV diagnosis were considered. RESULTS: Among the 85 studied patients, at least 81.2% were MSM. Respectively, 47.6%, 39.0%, 11.0% and 2.4% were infected with genotypes 1a, 4d, 3a and 2k. At least 91.8% were co-infected with HIV. HCV re-infection was evidenced for 24.7% of patients and STIs for 20.0% of patients. Twenty-two transmission chains were identified, including 52 acute hepatitis C (11 pairs and 11 clusters from three to seven patients). CONCLUSIONS: These results revealed strong clustering of acute HCV infections. Thus, rapid treatment of both chronic and acute infections is needed among this population to decrease the prevalence of HCV, in combination with preventive behavioural interventions

LOW LEVEL OF BASELINE RESISTANCE IN RECENTLY HCV INFECTED MEN WHO HAVE SEX WITH MEN WITH HIGH-RISK BEHAVIORS

International audienceBackground: The presence of baseline HCV resistance-associated substitutions (RASs) can impair treatment outcome by Direct-Acting Antivirals. We investigated the prevalence of pretreatment HCV resistance among recently HCV infected MSM with high risk behaviors, either 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 pretreatment samples of 72 subjects using Illumina Miseq paired-end sequencing technologies. UDS data was analyzed by Smartgene® platform. RASs mentioned in literature were analyzed and interpreted depending on genotypes (GT) at 10% cut-off.Results: HCV genotyping showed 36 (50%) GT1a, 31 (43.1%) GT4d, and 5 (6.9%) GT3a infections. Fifty-five (76.4%) patients were co-infected with HIV and 15 (20.8%) received PrEP. In GT1a virus, 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 (46.7%) viruses. No NS3-RASs were detected in GT4d and 3a 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.Conclusions: A low level of RASs to NS3 and NS5A inhibitors on pretreatment samples was detected in the study population. Our findings reassure the clinical management of HCV infection in this high-risk population

Shared HCV Transmission Networks Among HIV-1–Positive and HIV-1–Negative Men Having Sex With Men by Ultradeep Sequencing

International audienceObjective: Several studies reported hepatitis C virus (HCV) transmission networks among men having sex with men (MSM) in Europe and the spread of HCV strains from HIV-HCV coinfected toward HCV monoinfected MSM. We aimed to investigate HCV transmission dynamics among HIV-positive and HIV-negative MSM by ultradeep sequencing (UDS).Design and methods: NS5B fragment (388 bp) was sequenced from virus of 50 HIV-positive and 18 HIV-negative patients diagnosed with recent HCV infection. UDS data were analyzed by Geneious (version 10.3.2). Phylogenetic trees were constructed by FastTree (version 2.1) and submitted to ClusterPicker (version 1.2.3) for transmission chain detection at different thresholds of maximum genetic distance (MGD) (3% for Sanger, 3% and 4.5% for UDS).Results: Ten, 17, and 18 HCV transmission chains were identified by Sanger at 3%, UDS at 3% and at 4.5% of MGD, respectively. Of 68 subjects enrolled, 38 (55.9%), 38 (55.9%), and 43 (65.3%) individuals were involved in transmission networks found by Sanger at 3%, UDS at 3%, and at 4.5% of MGD, respectively. Mixed transmission chains including HIV-positive and HIV-negative subjects were detected for 8/10 chains by Sanger at 3%, for 9/17 by UDS at 3%, and for 10/18 by UDS at 4.5% of MGD. Overall, the number of HIV-negative individuals clustering with HIV-positive ones was 9/18 by Sanger, 9/18 by UDS at 3%, and 10/18 by UDS at 4.5% of MGD.Conclusions: HIV-positive and HIV-negative MSM shared HCV transmission networks, which emphasizes the need for HCV surveillance and prevention measures in these communities regardless of the HIV status

Acceptability of on-site rapid HIV/HBV/HCV testing and HBV vaccination among three at-risk populations in distinct community-healthcare outreach centres: the ANRS-SHS 154 CUBE study

International audienceBackground: 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

Uncommon Detection of Mixed HCV Genotype Infections in Recently Infected Men Who Have Sex with Men

International audienceINTRODUCTION: 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