BACKGROUND: The prolonged effectiveness of antiretroviral therapy (ART) in a developing country is not well established. METHODS: An observational database was established at the HIV clinic of the Almenara Hospital in Lima, Peru in 1996. All 564 initially antiretroviral-naive HIV-infected persons (mean CD4 count of 91 cells/mm) who received combination ART were followed over time. RESULTS: The overall survival rate was 96% at year 2, 94% at year 4, and 91% at year 5. Among persons who initiated therapy with CD4 counts <100 cells/mm, the overall survival rate at 3 years was 95%. Opportunistic infections while on ART occurred in 20% of persons. Patients who received 2 reverse transcriptase (RT) inhibitors plus a protease inhibitor had slightly better survival rates and less opportunistic disease in the first year of therapy as compared with those receiving 2 RT inhibitors and a nonnucleoside reverse transcriptase inhibitor or 3 RT inhibitors. CONCLUSIONS: This study demonstrates the long-term effectiveness of ART in a developing country urban setting. It provides evidence of the importance of continuing global financing initiatives to provide widespread HIV therapy for countries in the developing world. © 2007 Lippincott Williams & Wilkins, Inc.