Substituting Abacavir for Stavudine in Children Who Are Virally Suppressed without Lipodystrophy: Randomized Clinical Trial in Johannesburg, South Africa

Objectives: Abacavir has replaced stavudine in antiretroviral therapy (ART) regimens because it has largely been phased out as a result of toxicity concerns; this loss has reduced further the already-limited drug options for children. Few data regarding virologic and metabolic outcomes among children who undergo substitution of stavudine exist. We evaluated the effects of preemptive substitution of abacavir for stavudine in children initially without lipodystrophy and virally suppressed on a stavudine-containing regimen. Methods: At Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa, virally suppressed human immunodeficiency virus (HIV)-infected children ≥36 months of age without lipodystrophy were randomly assigned to continue taking stavudine as part of their ART regimen (n = 106) or to have abacavir substituted for stavudine (n = 107). The children were followed for 56 weeks after randomization in the context of a larger trial of treatment options for ART-experienced children. Results: The mean age of the children was 4.3 years, and the mean duration of ART before random assignment was 3.5 years. No differences in virological outcomes, CD4 response, growth, or dyslipidemia were noted between the stavudine and abacavir groups. By 56 weeks, children in the abacavir group had less clinically detected lipodystrophy (4.7% vs 16%, respectively), a higher proportion of leg fat relative to total fat (0.243 vs 0.230, respectively; P =. 006), and a lower trunk/leg-skinfold ratio (0.547 vs 0.569, respectively; P =. 003) than the children in the stavudine group. Conclusion: Substituting abacavir for stavudine did not compromise virological response to treatment and was associated with significantly less lipodystrophy. These results support recommendations that favor abacavir in this population.