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Construct percentile curves for 6-month gain in weight, height, CD4 cell count, and CD4 percentage (CD4%) in children initiating ART, and to assess the association between lower percentiles and subsequent ART responses.Cohort of 1394 HIV-infected children initiating ART between April 2004 and March 2008, Johannesburg, South AfricaThe generalized additive model for location, scale, and shape was used to construct percentile curves for 6-month gain in weight, height, CD4 cell count, and CD4%. Cox proportional models were used to assess the association between lower percentiles of each distribution and death, virological suppression, and treatment failure between 6 to 36 months post-ART initiation.Lower percentiles for gain in weight, CD4, and CD4% count after 6 months of ART, but not height, were associated with poor subsequent treatment outcomes independent of baseline characteristics, with increasing strength of association as percentiles decreased. Age-specific 6-month post-ART weight gain in our cohort was substantially higher compared with 6-month weight gain in non-HIV-infected American children of the Fels Institute cohort and the attained weight-for-age at 6 months post-ART plotted on WHO weight-for-age growth charts were not associated with subsequent treatment outcomes.Gain in CD4% in the first 6 months of ART was the best predictor of poor subsequent ART outcomes. In areas with limited access to CD4%, weight gain post-ART using our newly developed reference distributions for HIV-infected children on ART is a good alternative to CD4%, and clearly superior to the commonly used ‘Road-to-Health’ weight-for-age charts.