Abstract
Background
Direct-acting antivirals (DAAs) have substantially increased the rate of sustained virologic response in patients with hepatitis C compared with interferon therapy (IFN), while causing fewer adverse events. However, five recent case series and retrospective studies (Table 1) have reported a possible link between DAA treatment for hepatitis C and reactivation of varicella-zoster virus (VZV). Reported VZV reactivation rates in these studies were 0.23%, 0.72%, 1.50%, 1.74%, and 8.00%.
Methods
To further investigate these reported observations, we analyzed 37 prospective registrational DAA clinical trials, including 13,816 subjects in our analysis. Treatment arms were classified as DAA (N = 7,901), DAA + ribavirin (RBV) (N = 4,348), placebo (N = 997), DAA + IFN (N = 327), or IFN (N = 243). 1,068 (8%) subjects were HIV-coinfected, and 9,024 (65%) subjects were over age 50, both known risk factors for VZV reactivation. Herpes zoster (HZ) events occurring while on-treatment or during follow-up were identified using MedDRA preferred terms.
Results
We identified 36 (0.26%) subjects with HZ events. Thirty-two cases occurred during treatment, and 4 during follow-up. One event was considered severe, and the remaining were mild or moderate in severity. Of the 36 total cases reported, 11 (0.14%) were in DAA arms, 21 (0.48%) were in DAA+RBV arms, 4 (0.40%) were in placebo arms, and none were in DAA+IFN or IFN arms (Table 2). For a more direct comparison, we examined a subset of eight trials (N = 3835) containing both a DAA or DAA+RBV arm and a placebo arm. Of the 8 (0.21%) cases reported, 4 (0.14%) were in the DAA/DAA +RBV arms (N = 2838), and 4 (0.40%) were in the placebo arms (N = 997). While rates of VZV reactivation were increased for HIV-coinfected subjects (0.47% vs. 0.24%) and those over age 50 (0.31% vs. 0.17%) (Table 3), they remained similar to or lower than rates reported in previous studies (Table 1).
Conclusion
Data from prospective DAA clinical trials including 13,816 subjects do not provide evidence for an association between DAAs and VZV reactivation as reported in recent case series and retrospective studies. Low rates of VZV reactivation were observed, particularly in low-risk groups such as those below the age of 50, as would be expected in naturally occurring reactivation.
Disclosures
All authors: No reported disclosures.
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