Effectiveness of Pediatric Antiretroviral Therapy in Resource-Limited Settings: A Systematic Review and Meta-analysis

Background. Responses to antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected children in resource-limited settings have recently been reported, but outcomes vary. We sought to derive pooled estimates of the 12-month rate of virologic suppression (HIV RNA, <400 copies/mL) and gain in CD4 cell percentage (Delta CD4%) for children initiating ART in resource-limited settings. Methods. We conducted a systematic review and meta-analysis of published reports of HIV RNA and CD4 outcomes for treatment-naive children aged 0-17 years old by means of the Medline, EMBASE (Excerpta Medica Database), and LILACS (Latin American and Caribbean Health Sciences Literature) electronic databases and the Cochrane Clinical Trials Register. Pooled estimates of the reported proportion with HIV RNA <400 copies/mL and Delta CD4% after 12 months of ART were derived using patient-level estimates and fixed-and random-effects models. To approximate intention-to-treat analyses, in sensitivity analyses children with missing 12-month data were assumed to have HIV RNA>400 copies/mL or Delta CD4% of zero. Results. In patient-level estimates after 12 months of ART, the pooled proportion with virologic suppression was 70% (95% confidence interval [CI], 67%-73%); the pooled Delta CD4% was 13.7% (95% CI, 11.8%-15.7%). Results from the fixed-and random-effects models were similar. In approximated intention-to-treat analyses, the pooled estimates decreased to 53% with virologic suppression (95% CI, 50%-55%) and to a Delta CD4% of 8.5% (95% CI, 5.5%-11.4%). Conclusions. Pooled estimates of reported virologic and immunologic benefits after 12 months of ART among HIV-infected children in resource-limited settings are comparable with those observed among children in developed settings. Consistency in reporting on reasons for missing data will aid in the evaluation of ART outcomes in resource-limited settings.