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To explore the relationship between hepatitis C virus (HCV)/HIV coinfection and responses to initial antiretroviral treatment (ART).Four AIDS Clinical Trials Group HIV treatment studies’ data were combined to compare initial ART responses between HCV/HIV-coinfected and HIV-monoinfected patients as evaluated by virologic failure, CD4+ cell measures, occurrence of AIDS/death and grade 3/4 safety events, using Kaplan–Meier estimates and proportional hazard, regression and mixed effects models, adjusting for baseline covariates.Of the 3041 included participants, 81% were men, 19% had prior history of AIDS, the median (25th, 75th percentile) baseline HIV RNA was 4.72 (4.38–5.18) log10 copies/ml, and the median (25th, 75th percentile) baseline CD4+ cell count was 216.0 (76.5–327.0) cells/μl. The 279 HCV/HIV-coinfected individuals were older (44 vs. 37 years), more likely to be black non-Hispanic (47 vs. 36%), and previous/current intravenous drug user (52 vs. 5%) than the 2762 HIV-monoinfected patients (all P values <0.001). HCV/HIV coinfection was associated with earlier virologic failure, hazard ratio (95% confidence interval): 1.43 (1.07–1.91); smaller mean CD4+ cell increase and CD4+% increase [−33.8 (−52.2 to −15.4) cells/μl and −1.16% (−1.43 to −0.89%), respectively] over a median of 132 weeks of follow-up; earlier occurrence of grade 3/4 safety event, hazard ratio 1.51 (1.26–1.81); and increased AIDS/mortality, hazard ratio 2.10 (1.31–3.37). Treatment effects comparing antiretroviral regimens were not significantly different by HCV/HIV coinfection status.HCV/HIV coinfection is associated with attenuated response to ART. Results support earlier initiation of HIV therapy and increased monitoring of those initiating ART with HCV/HIV coinfection.