Time to direct-acting antiviral initiation and liver-related events in people with HIV and hepatitis C virus

Abstract

Objective: People with HIV-hepatitis C virus (HCV) co-infection need antiretroviral treatment (ART) to suppress HIV and direct-acting antivirals (DAAs) to cure HCV. ART is typically prioritized, but delays in DAA initiation may increase the risk of liver-related events and HCV transmission to others.

Design: Target trial emulation with observational data collected in routine clinical practice from a collaboration of cohorts from Europe and North America.

Methods: We included DAA-naive adults with HIV-HCV co-infection who achieved HIV virologic suppression (HIV RNA <50 copies/ml) after starting ART between 2013 and 2020. We estimated the probability of not initiating DAAs at 6 and 36 months after HIV virologic suppression and emulated a target trial of early (≤6 months after HIV virological suppression) versus delayed (>6 months) DAA initiation and the 36-month risk of liver-related events (liver decompensation or hepatocellular carcinoma).

Results: Of 862 eligible individuals (median age 46 years; interquartile range 36-56), 14% were women, and 52% had a history of injection drug use. The 6-month and 36-month probabilities of not initiating DAA were 58% [95% confidence interval (CI): 55-61] and 24% (21-27), respectively. The 36-month risk of liver-related events was 1.1% (0.4-2.0) for early initiation and 1.7% (0.7-2.5) for delayed initiation; risk difference -0.5% (-1.2 to 0.4).

Conclusion: Almost one-quarter of people with HIV-HCV co-infection on ART had not initiated DAA 3 years after HIV virologic suppression. Because the 3-year risk of liver-related events was low, estimates of the impact of delayed DAA initiation were imprecise.

Keywords: HIV-virologic suppression; HIV–hepatitis C virus co-infection; direct-acting antivirals; liver-related events; target trial emulation.