Barriers to care after Hepatitis C diagnosis: an implementation study of assisted self-testing among people who use drugs in Johannesburg.

People who inject drugs (PWID) and people who use drugs (PWUD) bear a disproportionate burden of hepatitis C virus (HCV) infection globally. In South Africa, HCV testing and treatment remain limited outside externally funded projects. This study investigated the implementation feasibility of assisted HCV self-testing (HCVST) among PWID and PWUD in Johannesburg. Between 12th May 2023 and 28th March 2024, participants were recruited to an implementation study across mobile harm reduction sites and a central clinic. Participants performed self-tests using either oral-fluid or blood-based HCV antibody rapid tests. Reactive results were followed by on-site venous sampling for confirmatory RNA testing and referral for direct-acting antiviral (DAA) therapy at a centralized facility. We describe HCV case-detection, care cascade progression, and behavioral risk factors associated with HCV reactivity using logistic regression. Of 1,566 participants tested, 998 (63.7%) were HCV reactive. The median age was 31 years (IQR 28-35); 82.2% were male and 77.1% identified as PWID. Ever injecting drugs (OR 35.6, 95% CI 23.6-56.0), frequent injecting ([≥] daily: OR 36.7, 95% CI 25.1-55.3), and recent needle sharing (OR 7.3, 95% CI 5.8-9.3) were the strongest predictors of HCV reactivity. Histories of incarceration were also independently associated with HCV reactivity (OR 3.2, 95% CI 2.6-4.0). Despite high self-testing acceptability, progression through the care cascade was limited: among 854 RNA-confirmed infections, only 147 (17.2%) were prioritized for treatment, with three participants achieiving sustained virologic response. Thematic analysis identified fear of needles, poor venous access, and structural barriers, notably centralized treatment delivery, as key impediments to linkage. This study showed a high burden of HCV among PWID and PWUD in Johannesburg and demonstrates that assisted HCVST is acceptable. Centralized treatment models severely constrained linkage to care. Simplified delivery of treatment is critical in transforming diagnosis into cure.