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Incidence of HCV reinfection among people with HIV prior to and during periods of limited and broad access to direct-acting antiviral therapies for HCV in five countries

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BACKGROUND: Direct-acting antivirals (DAA) may reduce HCV incidence through a treatment-as-prevention effect. Reinfection incidence after successful treatment has been a major concern for HCV elimination, particularly among people with HIV (PHIV). We aim to assess changes in HCV reinfection incidence following limited and broad DAA introduction among PHIV.
METHODS: We used data from six cohorts from the International Collaboration on Hepatitis C Elimination in HIV-coinfection (InCHEHC), including data from the Netherlands, Switzerland, Australia, Spain, and France (2010-2019). Participants were considered at risk of reinfection if they had a HCV positive test followed by spontaneous or treatment clearance. We measured the incidence of first reinfection per participant. Time zero was the first negative HCV RNA test indicating treatment or spontaneous clearance. Data were censored at the last negative HCV RNA test or infection date, which was estimated as the midpoint between the last negative and first positive test dates. The rate of reinfection was compared between three periods: prior to DAA access, and during limited access, and broad access to DAA in each jurisdiction using a piecewise exponential survival model, with a fixed effect for risk group (men who have sex with men [MSM], people who inject drugs [PWID] vs. other/unknown) and a random intercept at the cohort level.
RESULTS: Overall, 2,818 (57%) MSM, 1237 (25%) PWID, and 880 other participants were included. The median (IQR) age at spontaneous or treatment clearance was 47 (40-53). During 13,527 person-years (py), we observed 790 reinfections (5.8 per 100py, 95%CI 5.4-6.3). Relative to the pre-DAA period, reinfection incidence was 25% lower in the limited DAA access period (IRR: 0.75, 95%CI 0.62-0.91), and 44% lower in the broad access period (IRR: 0.56, 95%CI 0.48-0.66). Compared to MSM, reinfection incidence was 54% lower in PWID (IRR=0.46, 95%CI 0.37-0.56), and 57% lower in those with other/unknown risks (IRR=0.43, 95%CI: 0.34-0.55).
CONCLUSIONS: HCV reinfection rates among PHIV were high prior to DAA introduction, particularly among MSM. Our data suggests that DAA introduction was associated with declines in HCV reinfection incidence rates among PHIV. With HCV treatment uptake resulting in a growing pool of individuals at risk of reinfection, continued monitoring is warranted.