Frequent Longitudinal Sampling of Hepatitis C Virus Infection in Injection Drug Users Reveals Intermittently Detectable Viremia and Reinfection
ABSTRACT Background. Detection of hepatitis C virus (HCV) reinfection and intercalation (i.e., intermittent recurrent bouts of viremia with homologous virus interspersed with aviremic periods) requires extensive and frequent evaluation and viral sequencing.Methods. HCV infection outcomes were studied prospectively in active IDU with recurrent HCV RNA positive tests after serial negative results. HCV viremia and viral sequences (Core/E1) were assessed from monthly blood samples.Results. Viral clearance, reinfection and intercalating infection were all detected. Among 44 participants with apparently resolved HCV (26 incident HCV clearers and 18 enrolled with already resolved infection), 36 (82%) remained persistently HCV RNA negative, but 8 demonstrated intermittent recurrent viremia. Four of these (50%) had confirmed reinfection with a heterologous virus; three demonstrated viral intercalation, and one was not classifiable as either. Estimated incidence of first reinfection was 5.4/100 PY; (95% CI, 2.0, 14.5). Six (75%) participants, including three of four of those with reinfection, demonstrated sustained viral clearance for a median of 26 months since last HCV RNA test.Conclusions. These results show that frequent monitoring and viral sequencing are required to correctly assess HCV outcomes and estimate incidence of reinfection (which was previously overestimated). Sustained clearance may take many months and occur after episodes of reinfection and viral intercalation. Three of four subjects who had confirmed reinfection showed evidence of long term clearance. Viral intercalation occurs with significant frequency. Further studies of these events, especially immunological are needed to inform HCV clinical care and vaccine development.
Full-textDOI: · Available from: Michael P Busch, Jan 21, 2015
- SourceAvailable from: Xiomara V Thomas[Show abstract] [Hide abstract]
ABSTRACT: Most new cases of hepatitis C virus (HCV) infections in the developed world are associated with injection drug use. However, treatment for people who inject drugs (PWID) is controversial, as successful treatment risks being followed by new infection. Reinfection after sustained virologic response has been reported, but is the risk so great that treatment should be withheld from this large HCV population? Preliminary evidence suggests that the reinfection incidence is low, but studies to date have been limited by small sample size and few cases of reinfection. In this review, we assess data from studies among PWID of HCV reinfection following treatment to give a reasonable estimate on how frequently reinfection appears and try to characterize those most at risk, The observation that spontaneous clearance of HCV reinfection following treatment occurs is suggestive of a partial protective immunity against persistent infection.
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ABSTRACT: Hepatitis C virus (HCV) chronically infects over 180 million people worldwide, with over 350,000 estimated deaths attributed yearly to HCV-related liver diseases. It disproportionally affects people who inject drugs (PWID). Currently there is no preventative vaccine and interventions feature long treatment durations with severe side-effects. Upcoming treatments will improve this situation, making possible large-scale treatment interventions. How these strategies should target HCV-infected PWID remains an important unanswered question. Previous models of HCV have lacked empirically grounded contact models of PWID. Here we report results on HCV transmission and treatment using simulated contact networks generated from an empirically grounded network model using recently developed statistical approaches in social network analysis. Our HCV transmission model is a detailed, stochastic, individual-based model including spontaneously clearing nodes. On transmission we investigate the role of number of contacts and injecting frequency on time to primary infection and the role of spontaneously clearing nodes on incidence rates. On treatment we investigate the effect of nine network-based treatment strategies on chronic prevalence and incidence rates of primary infection and re-infection. Both numbers of contacts and injecting frequency play key roles in reducing time to primary infection. The change from "less-" to "more-frequent" injector is roughly similar to having one additional network contact. Nodes that spontaneously clear their HCV infection have a local effect on infection risk and the total number of such nodes (but not their locations) has a network wide effect on the incidence of both primary and re-infection with HCV. Re-infection plays a large role in the effectiveness of treatment interventions. Strategies that choose PWID and treat all their contacts (analogous to ring vaccination) are most effective in reducing the incidence rates of re-infection and combined infection. A strategy targeting infected PWID with the most contacts (analogous to targeted vaccination) is the least effective.PLoS ONE 11/2013; 8(11):e78286. DOI:10.1371/journal.pone.0078286 · 3.23 Impact Factor
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ABSTRACT: Hepatitis C virus reinfection and spontaneous clearance of reinfection were examined in a highly characterised cohort of 188 people who inject drugs over a five-year period. Nine confirmed reinfections and 17 possible reinfections were identified (confirmed reinfections were those genetically distinct from the previous infection and possible reinfections were used to define instances where genetic differences between infections could not be assessed due to lack of availability of hepatitis C virus sequence data). The incidence of confirmed reinfection was 28.8 per 100 person-years (PY), 95%CI: 15.0-55.4; the combined incidence of confirmed and possible reinfection was 24.6 per 100 PY (95%CI: 16.8-36.1). The hazard of hepatitis C reinfection was approximately double that of primary hepatitis C infection; it did not reach statistical significance in confirmed reinfections alone (hazard ratio [HR]: 2.45, 95%CI: 0.87-6.86, p=0.089), but did in confirmed and possible hepatitis C reinfections combined (HR: 1.93, 95%CI: 1.01-3.69, p=0.047) and after adjustment for the number of recent injecting partners and duration of injecting. In multivariable analysis, shorter duration of injection (HR: 0.91; 95%CI: 0.83-0.98; p=0.019) and multiple recent injecting partners (HR: 3.12; 95%CI: 1.08-9.00, p=0.035) were independent predictors of possible and confirmed reinfection. Time to spontaneous clearance was shorter in confirmed reinfection (HR: 5.34, 95%CI: 1.67-17.03, p=0.005) and confirmed and possible reinfection (HR: 3.10, 95%CI: 1.10-8.76, p-value=0.033) than primary infection. Nonetheless, 50% of confirmed reinfections and 41% of confirmed or possible reinfections did not spontaneously clear. Conclusions: Hepatitis C reinfection and spontaneous clearance of hepatitis C reinfection were observed at high rates, suggesting partial acquired natural immunity to hepatitis C virus. Public health campaigns about the risks of hepatitis C reinfection are required.PLoS ONE 11/2013; 8(11):e80216. DOI:10.1371/journal.pone.0080216 · 3.23 Impact Factor