PURGE-C was a phase II, open-label, single-arm trial evaluating the efficacy, safety, and tolerability of 4 weeks of glecaprevir/pibrentasvir (G/P) for early HCV primary infection (or reinfection).  Adults with any genotype were enrolled across multiple centers in the U.S. and Brazil.  Participants with known pre-existing cirrhosis, hepatitis B infection or acute hepatitis A, or other causes of chronic liver disease were excluded.  People with HIV were included if they were virally suppressed with CD4 > 100 cells/mm³, and not on ART with potential drug-drug interactions with G/P.  Among 45 participants (median age 36 years, 1 assigned female at birth), 84% had primary HCV infection and 16% had reinfection.  Median HCV RNA was 5.3 log₁₀ IU/mL and 71% had genotype 1.  38/45 (84%) achieved SVR12.  Median HCV RNA among participants with virologic failure was higher at baseline than among participants not experiencing virologic failure.  For participants who did not initially achieve SVR12, retreatment was offered (study “Step 2”): no resistance mutations were identified in post-treatment samples of people with genotypes 1 and 3.  Three received retreatment with G/P (without ribavirin) for 16 weeks and one participant received SOF/VEL/VOX for 12 weeks.  Another participant received SOF/VEL/VOX for 12 weeks outside of Step 2.  Among participants with known outcomes after retreatment, all achieved SVR12.

Four weeks of glecaprevir/pibrentasvir achieved SVR12 in almost 85% of participants with early HCV infection or reinfection in this study.  Treatment was well tolerated and safe.  Although SVR rates were lower than those using longer courses of G/P in early infection, several promising findings emerged.  Most virologic failures occurred in people with higher baseline HCV RNA, no emergent resistance mutations were detected, and retreatment outcomes were highly favorable.  Altogether, these analyses suggest that short course of therapy may be a viable approach for some people with early HCV infection, carefully balancing treatment access, uptake, care engagement, and other important outcomes such as transmission prevention.