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Detection of HCV-Specific IFN-? Responses in HCV Antibody and HCV RNA Negative Injecting Drug Users.

ABSTRACT: BACKGROUND:Detectable HCV-specific cellular immune responses in HCV antibody and RNA negative people who inject drugs (PWID) raise the question of whether some are resistant to HCV infection. Immune responses from people who have been exposed to hepatitis C virus (HCV) and remain anti-HCV negative are of interest for HCV vaccine development; however, limited research addresses this area. OBJECTIVES:In a cohort of HCV antibody and RNA negative PWID, we assessed whether the presence of HCV-specific IFN-? responses or genetic associations provide any evidence of protection from HCV infection. PATIENTS AND METHODS:One hundred and ninety-eight participants were examined longitudinally for clinical, behavioral, social, environmental and genetic characteristics (IFNL3 genotype [formally IL-28B] and HLA type). Sixty-one of the 198 participants were HCV antibody and RNA negative, with 53 able to be examined longitudinally for HCV-specific IFN-? ELISpot T cell responses. RESULTS:Ten of the 53 HCV antibody and RNA negative participants had detectable HCV-specific IFN-? responses at baseline (18%). The magnitude of IFN-? responses averaged 131 +/- 96 SFC/106 PBMC and the breadth was mean 1 +/- 1 pool positive. The specificity of responses were mainly directed to E2, NS4b and NS5b. Participants with (10) and without (43) HCV-specific IFN-? responses did not differ in behavioral, clinical or genetic characteristics (P > 0.05). There was a larger proportion sharing needles (with 70%, without 49%, P = 0.320) and a higher incidence of HCV (with 35.1 per 100 py, 95% CI 14.6, 84.4, without 16.0 per 100 py, 95% CI 7.2, 35.6, P = 0.212) in those with IFN-? responses, although not statistically significant. Half the participants with baseline IFN-? responses became HCV RNA positive (5/10), with one of these participants spontaneously clearing HCV. The spontaneous clearer had high magnitude and broad Th1 responses, favorable IFNL3 genotype and favorable HLA types. CONCLUSIONS:This study demonstrated the detection of HCV-specific IFN-? responses in HCV antibody and RNA negative individuals, with a tendency for HCV-specific IFN-? responses to be associated with HCV exposure. The potential role of HCV-specific IFN-? responses in those who remained HCV RNA negative is of value for the development of novel HCV therapeutics.

SUBMITTER: Flynn JK

PROVIDER: S-EPMC3909641 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Detection of HCV-Specific IFN-γ Responses in HCV Antibody and HCV RNA Negative Injecting Drug Users.

Flynn Jacqueline K JK Sacks-Davis Rachel R Higgs Peter P Aitken Campbell C Moneer Sarah S Suppiah Vijay V Tracy Lilly L Ffrench Rosemary R Bowden Scott S Drummer Heidi H George Jacob J Bharadwaj Mandvi M Hellard Margaret M

Hepatitis monthly 20140108 1

<h4>Background</h4>Detectable HCV-specific cellular immune responses in HCV antibody and RNA negative people who inject drugs (PWID) raise the question of whether some are resistant to HCV infection. Immune responses from people who have been exposed to hepatitis C virus (HCV) and remain anti-HCV negative are of interest for HCV vaccine development; however, limited research addresses this area.<h4>Objectives</h4>In a cohort of HCV antibody and RNA negative PWID, we assessed whether the presence ...[more]

PMID: 24497881

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Project description:BACKGROUND: Currently, sharing of drug paraphernalia is the main form of HCV transmission worldwide. In South America, consistent findings indicate that shared sniffing equipment is an important factor in the spread of HCV among non-injecting drug users. Epidemiological data on the status of HCV infection in illicit drug users in the Amazon region are scarce, although reports of clinical cases of hepatitis or pathologies associated with HCV infection in other population groups are numerous. Thereby, this study investigated the prevalence, genotype frequency, and epidemiological factors associated with HCV infection in non-injecting drug users in the state of Pará, eastern Amazon. RESULTS: During 2008-2011, 300 non-injecting drug users attending drug-treatment centers participated in this study. Most non-injecting drug users were male (63.7%). The mean age was 32.5 years. The non-injecting drugs most consumed were: cannabis (15.6%), cocaine paste (21.3%), and oxi cocaine (25.7%). Tobacco (60.9%) and alcohol (79.4%) were also commonly consumed. One hundred six (35.1%; CI 95%: 29.8 - 41.1) non-injecting drug users presented anti-HCV antibodies by EIA. The HCV-RNA prevalence was 28.0% (95% CI: 20.6 - 35.8). Genotypes 1 (76.9%) and 3 (23.1%) of HCV have been identified. A multivariate analysis demonstrated that HCV infection was independently associated with the following factors: "age (? 35 years)", "tattoos", "use of a needle or syringe sterilized at home", "shared use of drug paraphernalia", "uses drugs for more than 5 years", and "use of drugs everyday". CONCLUSIONS: This study revealed a high prevalence of HCV infection in non-injecting drug users, and most infections are occasioned by genotype 1. Likely, HCV transmission is associated with the tattoos, the use of needle or syringe sterilized at home by people over the age of 35 years, and sharing, time and frequency of use of non-injecting drugs. These findings should serve as an incentive for the establishment of a program of Hepatitis C prevention and control by the local public-health authorities in order to develop effective policies and strategies for contain the spread of HCV infection.

Dataset Information

Detection of HCV-Specific IFN-? Responses in HCV Antibody and HCV RNA Negative Injecting Drug Users.

Publications

Detection of HCV-Specific IFN-γ Responses in HCV Antibody and HCV RNA Negative Injecting Drug Users.

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