Predictors of Acute HCV Incidence in People with HIV: Insights from a Long-term Cohort Study

Persons living with HIV (PWH) remain at risk for hepatitis C virus (HCV) acquisition despite antiretroviral therapy, particularly among those who inject drugs or engage in high-risk sexual behaviors. We evaluated acute HCV incidence and associated risk factors in PWH, incorporating sex-specific differences and the use of Nucleic Acid Testing (NAT) methods, which were not addressed in previous analyses.

We assessed NAT-based HCV incidence from 1996-2011 in the ACTG ALLRT cohort, a long-term study of PWH after initiating antiretroviral therapy. Multivariable Poisson regression identified associations with self-reported injection drug use (IDU), and time-varying CD4+ count, HIV RNA level and increased ALT (grade ≥3). No sexual risk factors or non-IDU drug use data were available.

Among 4,015 PWH (18% women, n=703) with an initial negative HCV antibody result, there were 18,150 person-years (PY) of follow-up. Forty-two participants seroconverted, an incidence of 0.23 per 100 PY (95% CI: 0.17, 0.31). Incidence was lower in females (n=2) versus males (n=40; 0.06 vs 0.27 per 100 PY; p=0.04). Seroconversion was associated with time-updated HIV RNA ≥400 copies/mL (RR 2.7, 95% CI 1.4-5.1, p=0.003), time-updated grade ≥3 ALT (RR 4.7, 95% CI 1.6, 13.4, p=0.005), and IDU (RR 6.3, 95% CI 2.7, 14.4, p<0.001).

Our analysis showed that IDU history and unsuppressed HIV RNA were associated with HCV acquisition among PWH. Elevated ALT levels are consistent with the biology of acute/recent hepatitis and should trigger HCV RNA testing. These findings emphasize the need for targeted interventions to reduce HCV transmission risk in PWH.