Neurodevelopmental Benefits of Antiretroviral Therapy in Ugandan Children Aged 0–6 Years With HIV

Abstract

Background Insufficient data on neurodevelopmental benefits of antiretroviral therapy (ART) in children. Methods Prospective study of 329 mothers and children aged 0–6 years to assess neurodevelopment. Results stratified by the maternal (M) and child (C) HIV status (MHIV−/CHIV−, MHIV+/CHIV−, and MHIV+/CHIV+). Gross Motor, Visual Reception, Fine Motor, Receptive and Expressive Language scores assessed by Mullen Scales of Early Learning. Global cognitive function was derived from an Early Learning Composite score (ELC). Standardized Weight and Height for Age z-scores were constructed and the lowest 15% cutoff defined disability. Generalized linear models were used to estimate Prevalence Rate Ratios (PRR) adjusted for the child’s age, weight and height. In HIV-positive children, generalized linear models assessed the impact of ART initiation and duration on neurodevelopment. Results Compared to MHIV−/CHIV− children, HIV+ children were more likely to have global deficits in all measures of neurodevelopment except gross motor skills, whereas in MHIV+/CHIV− children, there was impairment in receptive language (adj.PRR=2.67, CI: 1·08, 6.60) and the ELC (adj.PRR=2.94, CI: 1.11, 7.82). Of the children born to HIV positive mothers, HIV+ children did worse than - MHIV+/CHIV− only in Visual Reception skills (adj.PRR=2.86; CI: 1.23–6.65). Of the 116 HIV+ children, 44% had initiated ART. Compared to ART duration of <12 months, ART durations 24–60 months was associated with decreased impairments in Fine Motor, Receptive Language, Expressive Language and ELC scores. Conclusions Longer duration on ART is associated with reduction of some neurologic impairment and early diagnosis and treatment of HIV+ children is a priority.

Comparison of developmental milestone attainment in early treated HIV-infected infants versus HIV-unexposed infants: a prospective cohort study

“…Previous studies have found deficits in language in HIV-infected children [25, 28–30]. We previously reported that use of LPV/r-based ART was associated with earlier age for speech in this cohort.…”

CNS Impact of Perinatal HIV Infection and Early Treatment: the Need for Behavioral Rehabilitative Interventions Along with Medical Treatment and Care

“…Research from high-income countries suggests that children treated with a protease inhibitor (PI) based antiretroviral (ARV) regimen have normal global cognition scores [4] and that ARV treatment duration is associated with a reduction in neurological impairment [5]. However, evidence is largely limited to subtype-B, which is responsible for only 11% of global HIV infections [6].…”

“…Using this approach, Laughton and colleagues documented in a randomized controlled trial that very early initiation of treatment with HAART among South African children with HIV resulted in better neurodevelopmental outcomes [11]. The same seems to be true in an observational study of very young Ugandan children [5]. …”

Nutritional and Immunological Correlates of Memory and Neurocognitive Development Among HIV-Infected Children Living in Kayunga, Uganda

“…Although long-term effects of ART in young children living in rural Uganda have been associated with better neurodevelopmental outcomes [23], no studies to date have examined whether being on ART affects working memory.…”