BACKGROUND Individuals with recent HCV infection may benefit from shortened duration therapy. These studies evaluated the efficacy and safety of response-guided regimens with pegylated interferon-α2a and ribavirin for people with recent HCV infection. METHODS Participants with recent hepatitis C (duration of infection ≤18 months) enrolled in the ATAHC II (pegylated interferon-α2a ± ribavirin) and DARE-C I (pegylated interferon-α2a, ribavirin and telaprevir) studies were included for analysis. Treatment duration was response-guided (ATAHC II: 8, 16, 24 or 48 weeks; DARE-C I: 8, 12 or 24 weeks) and dependent on time to first undetectable HCV RNA using Roche Taqman HCV RNA testing. The primary efficacy end point was sustained virological response at 12 weeks (SVR12) by intention-to-treat. Logistic regression analyses were used to identify predictors of SVR. RESULTS A total of 82 participants (62% HIV-positive) were enrolled in ATAHC II (treated, n=52) and 14 (79% HIV-positive) in DARE-C I. The predominant modes of HCV acquisition were injecting drug use (ATAHC II 55%, DARE-C I 36%) and sexual intercourse with a partner of the same sex (ATAHC II 39%, DARE-C I 64%). SVR12 was 71% in both ATAHC II (37/52) and DARE-C I (10/14) with 56% in ATAHC II receiving shortened therapy (8 or 16 weeks). SVR was associated with a rapid virological response (odds ratio 10.80; P=0.001). CONCLUSIONS The majority of participants were able to receive short duration response-guided therapy with pegylated interferon-α2a and ribavirin. Response-guided therapy for recent hepatitis C infection could be considered in the absence of available interferon-free therapies. ClinicalTrials.gov registry (ATAHC II: NCT01336010; DARE-C I: NCT01743521).