MSc (Med), Epidemiology and Biostatistics, Faculty of Health Sciences, University of the Witwatersrand / Objectives: To evaluate differences in virologic outcomes between adolescents and pre-adolescents initiated on HAART and to determine the patient baseline variables associated with virologic suppression. Design: Retrospective cohort study using routinely collected clinic and outcome data. Setting: Public sector HIV paediatric facility at Harriet Shezi Children’s Clinic (Chris Hani Baragwanath Hospital) Soweto, South Africa. Patients: HIV infected pre-adolescents (5 to < 11 years) and adolescents (11 to <18 years) initiating HAART between 1 April 2004 and 31 December 2008. Main outcomes and measures: Primary: virologic suppression (HIV viral load ≤ 400 copies/ml) and viral rebound (single HIV viral load ≥ 400 copies/ml after initial suppression) at 24, 48, 72 and 96 week follow up intervals. Secondary: determination of baseline variables associated with virologic suppression. Survival analysis was performed using the Kaplan Meier method and modelling was based on Cox proportional hazards. Results: Both groups exhibited similar incidence rates of virologic suppression by the 24th week from HAART initiation. Adolescents had a slightly lower incidence rate of early virologic suppression in comparison to pre-adolescents (197/100 person years vs. 203/100 person years). However, the observed difference was not statistically significant at 5% significance level (IRR: 0.97, 95%CI: 0.81 - 1.15). In a sub-group of children who had not virologically suppressed by the 24th week (168 days) of follow up, adolescents were 42% less likely to achieve virologic suppression after this time point than pre-adolescents ([IRR: 0.58, 95%CI: 0.35, 0.93). In the sub-group of all female participants, lower hazards of virologic suppression by the 24th week (aHR 0.76, 95%CI 0.59-0.99) and 96th week (aHR 0.70, 0.55-0.90) of follow up were observed among female adolescents when compared with female pre-adolescents. Additionally, clinically advanced disease was observed as a risk factor for non-virologic suppression by the 96th week of follow up among participants of all ages (aHR 0.75, 95%CI 0.64 -0.87). After 60 weeks from the initial virologic suppression, adolescents were twice more likely to experience rebound after this point than pre-adolescents (IRR: 2.33, 95%CI: 1.00 - 5.13). Conclusion: Given the potential for resistant strains of the HIV virus and the public health threat this presents, health care teams face complicated dilemmas regarding initiation of HAART to adolescents, particularly female adolescent patients who are likely to be non-adherent. Findings from the study advocate for intensified adherence and treatment support for all adolescents initiated on HAART to achieve virologic suppression within the first 6 months of treatment, a time after which they have been shown to exhibit inferior virologic suppression rates. Once virologic suppression has been attained, adolescents require prolonged treatment support to maintain long term virologic suppression at levels observed among pre-adolescents. We recommend further research into the comparison of virologic outcomes between pre-adolescents and adolescents on HAART, through prospective study designs. Qualitative study designs are also important to bridge the knowledge gaps on the barriers to HAART encountered by female adolescents.