No Association Between DAA Treatment for HCV Infection and Herpes Zoster Infection in Analysis of Data From 37 Clinical Trials

ABSTRACT Background and Aims Recent case series and retrospective studies have raised concerns that patients who receive direct-acting antiviral treatment for hepatitis C virus (HCV) infection are at increased risk of developing varicella-zoster virus infection (VZV reactivation). We investigated the relationship between DAA treatment and VZV reactivation by analyzing pooled participant-level data from 37 clinical trials of DAA agents. Methods We obtained demographic, adverse event, and laboratory data from 13,816 participants in 37 clinical trials submitted to the Food and Drug Administration for approval of DAA agents for treatment of HCV infection. Participants received DAAs (n=12,249), placebo (n=997), pegylated interferon (n=243), or a combination of DAAs and pegylated interferon (n=327). Occurrence of VZV reactivation was identified using systematically reported adverse event data. HCV virologic response was evaluated by measurement of HCV RNA. Results VZV reactivation occurred in 9.9 cases per 1000 person-years of DAA treatment (95% CI, 6.8–14.0 per 1000 person years). VZV reactivation occurred in 13.8 cases per 1000 person-years in the placebo group (95% CI, 3.5–37.5 per 1000 person years) and no participants in the pegylated interferon or combination DAA and pegylated interferon groups. Within the placebo-controlled trials there was no significant difference in VZV reactivation between DAA treatment and placebo. VZV reactivation was associated with age older than 40 years, female sex, and HIV-coinfection. We did not find an association between time of virologic response and time to VZV reactivation. Conclusion In an analysis of data from 37 trials, we found no evidence for an association between DAA treatment for HCV infection and increased risk of VZV reactivation.