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

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

Incidence of COVID-19 mRNA vaccine symptomatic breakthrough infections during Omicron circulation in adults with or without infection prior to vaccination

International audienceObjectives: COVID-19 vaccine breakthrough infections were frequently reported during circulation of the Omicron variant. The ANRS|MIE CoviCompareP study investigated these infections in adults vaccinated and boosted with BNT162b2 [Pfizer-BioNTech] and with/without SARS-CoV-2 infection before vaccination.Methods: In the first half of 2021, healthy adults (aged 18-45, 65-74 and 75 or older) received either one dose of BNT162b2 (n = 120) if they had a documented history of SARS-CoV-2 infection at least five months previously, or two doses (n = 147) if they had no history confirmed by negative serological tests. A first booster dose was administered at least 6 months after the primary vaccination, and a second booster dose, if any, was reported in the database. Neutralizing antibodies (NAbs) against the European (D614G) strain and the Omicron BA.1 variant were assessed up to 28 days after the first booster dose. A case-control analysis was performed for the 252 participants who were followed up in 2022, during the Omicron waves.Results: From January to October 2022, 78/252 (31%) had a documented symptomatic breakthrough infection after full vaccination: 21/117 (18%) in those who had been infected before vaccination vs. 57/135 (42%) in those who had not. In a multivariate logistic regression model, factors associated with a lower risk of breakthrough infection were older age, a higher number of booster doses, and higher levels of Omicron BA.1 NAb titers in adults with infection before vaccination, but not in those without prior infection.Conclusion: Our results highlight the need to consider immune markers of protection in association with infection and vaccination history