Correlates of age at attainment of developmental milestones in HIV-infected infants receiving early antiretroviral therapy.

BACKGROUND: Infant HIV-1 infection is associated with impaired neurologic and motor development. Antiretroviral therapy (ART) has the potential to improve developmental outcomes but the relative contributions of pre-ART disease status growth treatment regimen and ART response during infancy are unknown. METHODS: Kenyan ART-naive infants <5-months old initiated ART and had monthly assessment of age of full neck control unsupported walking and monosyllabic speech during 24 months of follow-up. Pre-ART and post-ART correlates of age at milestone attainment were evaluated using t tests or multivariate linear regression. RESULTS: Among 99 infants pre-ART correlates of later milestone attainment included: underweight and stunted (neck control walking and speech all P values <0.05) missed prevention of mother-to-child transmission (P = 0.04) (neck control) previous hospitalization World Health Organization (WHO) Stage III/IV low CD4 count and wasting (speech and walking all P values <0.05) and low maternal CD4 (speech P = 0.04). Infants initiated ART at a median of 14 days following enrollment. Infants receiving lopinavir/ritonavir-based versus nevirapine-based ART attained later speech (18.1 vs. 15.5 months P = 0.003). Adjusting for pre-ART level lower 6-month gain in CD4% was associated with later walking (0.18 months earlier per unit increase in CD4%; P = 0.004) and speech (0.12 months earlier per unit increase in CD4%; P = 0.05) and lower 6-month gains in weight-for-age (P = 0.009) height-for-age (P = 0.03) and weight-for-height (P = 0.02) were associated with later walking. CONCLUSION: In HIV-infected infants compromised pre-ART immune and growth status poor post-ART immune and growth responses and use of lopinavir/ritonavir-based versus nevirapine-based ART were each associated with later milestone attainment. The long-term consequences of these delays are unknown.