Abstract
BackgroundInfant HIV infection is associated with delayed milestone attainment. The extent to which effective antiretroviral therapy (ART) prevents these delays is not well defined.MethodsAges at attainment of milestones were compared between HIV-infected (initiated ART by age <5 months), and HIV-unexposed uninfected (HUU) infants. Kaplan Meier analyses were used to estimate and compare (log-rank tests) ages at milestones between groups. Adjusted analyses were performed using Cox proportional hazards models.ResultsSeventy-three HIV-infected on ART (median enrollment age 3.7 months) and 92 HUU infants (median enrollment age 1.6 months) were followed prospectively. HIV-infected infants on ART had delays in developmental milestone attainment compared to HUU: median age at attainment of sitting with support, sitting unsupported, walking with support, walking unsupported, monosyllabic speech and throwing toys were each delayed (all p-values <0.0005). Compared with HUU, the subset of HIV-infected infants with both virologic suppression and immune recovery at 6 months had delays for speech (delay: 2.0 months; P = 0.0002) and trend to later walking unsupported. Among HIV-infected infants with poor 6-month post-ART responses (lacking viral suppression and immune recovery) there were greater delays versus HUU for: walking unsupported (delay: 4.0 months; P = 0.0001) and speech (delay: 5.0 months; P < 0.0001).ConclusionsHIV infected infants with viral suppression on ART had better recovery of developmental milestones than those without suppression, however, deficits persisted compared to uninfected infants. Earlier ART may be required for optimized cognitive outcomes in perinatally HIV-infected infants.Trial registrationNCT00428116; January 22, 2007.
Highlights
Infant HIV infection is associated with delayed milestone attainment
We previously reported that greater CD4% gain over 6 months on antiretroviral therapy (ART) was associated with earlier age at walking and speech in early treated Kenyan infants, a majority of whom who presented with symptomatic HIV disease at ART [19]
Delayed milestones in HIV-infected versus HIV-unexposed uninfected (HUU) infants We previously reported that prior history of hospitalization, a World Health Organization (WHO) Stage 3 or 4 diagnosis, lower Weight-for-age zscore (WAZ), Height-for-age z-score (HAZ), and Weight-for-height z-score (WHZ) and lower maternal CD4 count were associated with later age at milestone attainment in HIV-infected infants [19]
Summary
Infant HIV infection is associated with delayed milestone attainment. The extent to which effective antiretroviral therapy (ART) prevents these delays is not well defined. In ART-treated HIV-infected children in the US, early (prior to age 5 years) plasma viral suppression [13] was associated with higher school-age IQ scores, supporting the hypothesis that effective ART in infancy may improve neurocognition; in this study children with better virologic responses to ART still had scores well below national norms. Recent data from the South African CHER study suggests that early ART is broadly beneficial in preserving neurocognitive function. In this randomized trial, asymptomatic infants without immunosuppression who received ART by 6–12 weeks of age had similar mental, social and locomotor scores as HIV-uninfected infants at 11 months of age [18]. Infants who received deferred ART (until symptomatic or meeting CD4 treatment criteria at the time) had lower locomotor scores, suggesting early HIV disease progression compromised outcomes
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