The study objective was to evaluate the effectiveness and durability of highly active anti-retroviral therapy (HAART) in perinatally HIV-1-infected children and adolescents and its predictors. A historical cohort study was done at IMIP's Hospital in Recife, Brazil. The study included 195 subjects, 102 (52.3%) had successful response to HAART with a mean time of any HAART use of 4.9 [standard deviation (SD) 2.5; min. 0.7, max. 9.9] years. The time to failure of first HAART was negatively associated with male sex [relative hazard (RH) = 0.5, p = 0.021) and living out of metropolitan area (RH = 0.4, p = 0.009), and associated with Centres for Diseases Control and Prevention (CDC) immunological Stage 1 (RH = 2.9, p = 0.003) and patients who were adherent (RH = 2.2, p = 0.003). HAART success rate and mean time durability was similar to developed country data. However, the main predictors of success were: female sex, living in a metropolitan area, CDC1 immunological category and adherence.