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To determine the efficacy of patient-selected treatment partners on virologic and adherence outcomes during first-line antiretroviral therapy.Randomized controlled trial.Between June 2006 and December 2007, 499 HIV-infected adults in Jos, Nigeria, were randomized to standard of care (SOC) or patient-selected treatment partner-assisted therapy (TPA). Each patient was followed for 48 weeks. Virologic outcomes, adherence to drug pick-up, CD4 cell counts, and mortality are reported.At week 24, undetectable viral load was achieved by 61.7% of patients in the TPA arm versus 50.2% of those receiving SOC [odds ratio (OR) = 1.58, 95% CI: 1.11 to 2.26, P < 0.05]. There was no significant difference at week 48: 65.3% versus 59.4% for TPA and SOC, respectively (OR = 1.28, 95% CI: 0.89 to 1.84, P > 0.05). The TPA group had more than 3 times the odds of at least 95% drug pickup adherence through week 24 (OR = 3.06, 95% CI: 1.89 to 4.94, P < 0.01) and almost twice the odds through week 48 (OR = 1.95, 95% CI: 1.29 to 2.93, P < 0.01). At week 48, there were no significant differences in CD4 cell count increases (t = −0.09, df = 404, P > 0.05) or mortality (10.6% vs. 6.1%) between TPA vs. SOC, respectively. Residence-to-clinic distance was significantly associated with virologic and adherence outcomes.Use of patient-selected treatment partners was associated with improved drug pickup adherence and initial virologic success but had no durable effect on attaining undetectable viral load.