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To assess the long-term survival, as well as the immunologic and virologic effectiveness, adherence, and drug resistance, in HIV-infected patients receiving highly active antiretroviral therapy (HAART) in one of the oldest and best-documented African cohorts.A prospective observational cohort study included the first 176 HIV-1-infected adults followed in the Senegalese government-sponsored antiretroviral therapy initiative launched in August 1998. Patients were followed for a median of 30 months (interquartile range, 21-36 months). HAART comprised 2 nucleoside reverse transcriptase inhibitors and either 1 protease inhibitor or 1 nonnucleoside reverse transcriptase inhibitor.At baseline, 92% of patients were antiretroviral naive and 82% had AIDS; the median CD4 count was 144 cells/mm3, and median viral load was 202,368 copies/mL. The survival probability was high (0.81 at 3 years; 95% CI, 0.74-0.86) and was independently related to a baseline hemoglobin level <10 g/dL and a Karnofsky score <90%. Antiviral efficacy was consistently observed during the 3 years of treatment (−2.5 to −3.0 log10 copies/mL; 60-80% of patients with viral load <500 copies/mL) and the CD4 count increase reached a median of 225 cells/mm3. Most patients reported good adherence (80-90%). The emergence of drug resistance was relatively rare (12.5%).This study shows that clinical and biologic results similar to those seen in Western countries can be achieved and sustained during the long term in Africa.