OBJECTIVE: People with HIV-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-naïve adults with HIV-HCV co-infection who achieved HIV virologic suppression (HIV RNA<50 copies/mL) after starting ART between 2013-2020. We 1) estimated the probability of not initiating DAAs at 6 and 36 months after HIV virologic suppression, and 2) 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 to 56), 14% were women, and 52% had a history of injection drug use. The 6 and 36-month probabilities of not initiating DAA were 58% (95% 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, 0.4). CONCLUSIONS: 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.Read less <