Background and Aims HLA Class I alleles are linked to spontaneous control of HCV and HIV-1, but for HCV the roles of particular alleles and corresponding CD8+ T-cell responses remain incompletely defined. We aimed to determine the correlations between these alleles and natural outcome of HCV and determine associated key T cell responses. Methods In a cohort of HCV individuals we determined HLA Class I alleles, HCV outcome, T-cell responses, and examined sequence data for mutational changes within key epitopes. Results Carriage of HLA-B*57 was associated with a higher rate of viral clearance [RR=2.0, 95% C.I. 1.2–3.4] while HLA-B*08 was associated with a lower rate [RR=0.34, 95% C.I. 0.1–0.9]. Two HLA-B*57 restricted T-cell epitopes were targeted in spontaneous clearance; subjects with chronic viremia expressing HLA-B*57 harbored HCV strains with a high frequency of mutations in key residues. HLA-B*57-mediated escape was supported by diminished immune recognition of these variants and acute HCV infection revealing viral evolution towards less recognized variants. Analysis of a genotype 1b strain from a single-source HCV outbreak in which HLA-B*57 was not protective revealed sequence variations that interfere with immunogenicity, thereby preventing HLA-B*57-mediated immune pressure. Conclusions Our data indicate a role of HLA-B*57-restricted CD8+ T cell responses in mediating spontaneous clearance and evolution in HCV infection, and viral strains containing epitope variants that are less recognized abrogate the protective effects of HLA-B*57. The finding that HLA-B*57-mediated antiviral immunity is associated with control of both HIV-1 and HCV suggests a common shared mechanism of a successful immune response against persistent viruses.

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Objectives The purpose of this study was to evaluate the feasibility and short-term impact of a brief opioid overdose prevention and mitigation training administered to detained youth at risk for witnessing an overdose. Methods Adolescents seen in the medical clinic in a youth detention center were screened to determine risk for witnessing an overdose. Eligible adolescents completed a pretraining assessment that included opioid witnessing experiences and knowledge of and attitudes toward opioid overdose prevention. Participants completed a one-on-one overdose first aid training, received a naloxone (Narcan) kit at release, and completed a posttraining assessment of knowledge and attitudes. At 1 month and 3 months postrelease, participants completed telephone interviews to report satisfaction and application of training concepts. Results A total of 39 adolescent residents participated in this pilot study. Rates of recruitment and retention, as well as high rates of witnessing opioid use and overdose, indicate that opioid overdose prevention interventions are warranted with this population. There were significant changes in knowledge, confidence, and readiness to intervene in an opioid overdose from pre- to posttraining. At follow-up, the majority of participants still possessed their naloxone, and all reported sharing information from the training with others and having a plan if they witnessed an overdose. One participant reported completion of an overdose reversal. Implications Opioid overdose prevention training with detained youth is feasible and shows promising impacts on knowledge and application, meriting the need for future research.

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