HCV reinfection among HIV‐positive men who have sex with men: A pragmatic approach
Authors: Thomas C.S. Martin, Gurmit Jagjit Singh, Myra McClure, Mark Nelson
Journal: Hepatology (2014)

Potential conflict of interest: Dr. Singh received grants from Gilead, Boehringer Ingelheim, and Janssen. To the Editor: In a recent edition of Hepatology, Abdelrahman et al.1 describe the use of next‐generation sequencing to investigate acute hepatitis C virus (HCV) treatment failures among human immunodeficiency virus (HIV)‐infected individuals. They show that among individuals with a null response, partial response, or relapse during HCV treatment with peg‐interferon alpha and ribavirin, the dominant strain of virus posttreatment was frequently a nondominant strain only detectable at low levels pretreatment. The authors generalized their findings, saying it was probable that in recent reinfection studies2 the majority of cases labeled as HCV reinfection were actually nondominant, low‐level variants present pretreatment that subsequently emerged following suppression of a dominant strain rather than true reinfection. In our study, "Hepatitis C virus reinfection incidence and treatment outcome among HIV‐positive MSM," we described the incidence and outcomes of 54 cases of reemergent HCV following treatment or spontaneous clearance of a prior infection.3 In the majority (93%), reemergent viremia occurred beyond 24 weeks following end‐of‐treatment (EOT) and were therefore designated as reinfection. Previous work has shown that HCV relapse beyond 24 weeks following EOT is rare, occurring in <1% of monoinfected and coinfected individuals, therefore providing strong support for reinfection rather than late relapse in our cohort.4 Unfortunately, Abdelrahman's results cannot easily be generalized to published reinfection studies. Indeed, only four cases (7%) included in our study had reemergent viremia before establishment of a sustained viral response (SVR) and would thus fall within their study population: only one of these was treated for their initial infection and this patient went on to be successfully treated for their reinfection, arguing against the emergence of a resistant nondominant minority variant. Importantly, even excluding these four individuals from our results, we still found high reinfection rates of 9.4/100 person‐years. Our reinfection outcomes were excellent, with a spontaneous clearance rate of 20% and SVR of 73% for genotypes 1+4 and 100% for genotypes 2+3 using peg‐interferon alpha and ribavirin. These results do not support the emergence of resistant low‐level variants as the mechanism of rebound but support reinfection with novel susceptible virus. Even if viral rebound is actually emergence of a nondominant HCV strain, our results suggest that, from a pragmatic point of view, retreatment would still be indicated and highly successful. Overall, we believe reinfection as a cause of reemergent viremia remains highly probable among HIV‐infected individuals who continue to place themselves at high risk of reexposure either through risky sexual practices or drug‐taking behaviors. Nevertheless, until deep sequencing studies are performed on paired samples for individuals who have reemergent HCV viremia beyond SVR, there will remain some uncertainty. In the era of direct‐acting antivirals (DAAs), reinfection will be of great interest as the cost of treatment rapidly escalates, thus supporting further epidemiological studies into potential prevention interventions.