Sunil S. Solomon, Aylur K. Srikrishnan, Allison M. McFall, Jiban Baishya, Mihili P Gunaratne, Ashwini Kedar, Pradeep Amrose, R. Balakrishnan, Jayaseelan Boobalan, Julie Evans, Bryan Lau, Stephan Ehrhardt, Mark Sulkowski, David L. Thomas, Gregory M. Lucas, M. Suresh Kumar, Shruti H. Mehta
BACKGROUND & AIMS: We evaluated impact of hepatitis C treatment adherence support among people who inject drugs (PWID) in India using a precision trial design. METHODS: Treatment naïve participants with a history of drug injection were recruited from community-based clinics across 7 cities. All received sofosbuvir/velpatasvir once/day for 12 weeks. Failure risk was defined a priori using a prognostic score including age, sex, income, homelessness, injection frequency, depressive symptoms, quality of life indicators and sexual partners. Elevated risk were randomized 3:2:1 to high (patient navigation [PN]+flexible directly observed therapy [≥1 dose/week observed]), medium (PN contact ≥every 2 weeks) or low intensity support. Minimal risk were randomized 1:2:3 to high, medium and low intensity support. Primary outcome was sustained virologic response (SVR; HCV RNA <LLOQ 24 weeks post-randomization; intention to treat). RESULTS: 3000 were randomized (1/2021-12/2022; 2048 minimal, 952 elevated risk), 2798 (93.3%) completed SVR assessment. In minimal risk participants, SVR was 62.6%, 60.8% and 68.3% in low, medium and high intensity support, respectively. In elevated risk participants, SVR was 48.4%, 45.5% and 50.8%. 51 experienced a serious adverse event (35 deaths). In minimal risk participants, we observed superiority of high intensity (adjusted relative risk vs. low [aRR] 1.09; 95% confidence interval [CI]: 1.00-1.19; p=0.04) not medium intensity (aRR 0.97; 95% CI: 0.90-1.05) support. In elevated risk participants, there was no impact (low vs. high 0.96; 95% CI: 0.80-1.15; medium vs. high 0.89; 95% CI: 0.77-1.04). Every 10% decrease in prognostic score was associated with 1.06 increase in SVR (95% CI: 1.04-1.08). CONCLUSIONS: Prognostic scores could help target interventions more efficiently; greater adherence support and/or novel interventions are needed to improve SVR for the highest risk. CLINICAL TRIAL NUMBER: ClinicalTrials.gov NCT04652804. IMPACT AND IMPLICATIONS: This trial represents one of the largest trials to date of hepatitis C treatment. Our results, which demonstrate limited impact of adherence support interventions and sub-optimal sustained virologic response (SVR) among community-based people who inject drugs (PWID), suggest that more intensive or different tools and or strategies will be needed to support HCV elimination in populations like PWID. At the same time, these results provide strong evidence for the use of prognostic scores in trials as well as potentially in the delivery of interventions particularly when resources are scarce.