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PREDICTORS OF NEURODEVELOPMENT
IN HIV-EXPOSED-UNINFECTED INFANTS
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Croi 2022
Abstract Body
Over one million HIV-exposed uninfected (HEU) children are born annually in sub-Saharan Africa (SSA). Some but not all studies have found increased risk of neurodevelopmental delay, hospitalization, and mortality in HEU children compared to HIV-unexposed uninfected (HUU) children, but predictors of this association remain poorly understood.
Mothers living with and without HIV were recruited with their infants (HEU and HUU, respectively) at 4-10 weeks of age during routine postnatal care at 6 clinics in Kenya between March-October 2021. Infant neurodevelopment was assessed using the Malawi Developmental Assessment Tool (MDAT), a validated instrument that scores social, language, fine motor, and gross motor domains. Multivariate linear and log binomial regression models assessed associations between infant HIV and ART exposure and neurodevelopment scores, adjusting for confounders selected a priori.
Compared to HUU infants (N=702), HEU infants (N=326) were slightly younger (6.2 vs. 6.4 weeks) and more likely to have an older mother with lower education and either unmarried or in a polygamous marriage. Among HEU infants, 50% received AZT+NVP regimens and 63% were exposed to maternal dolutegravir (DTG). Median maternal ART duration was 49.6 months (IQR: 13.3, 81.9), 87% of mothers were on ART pre-conception, and 95% of mothers were virally suppressed (VS) in pregnancy. Adjusting for infant age and sex, and maternal education and marital status, HEU and HUU infants had comparable MDAT scores in all four domains (Table 1). Among HEU infants, those receiving AZT+NVP regimens had significantly higher social and gross motor scores than those receiving NVP-alone (p<0.05). Furthermore, longer maternal ART duration was significantly associated with improved social and language scores (p<0.05). Maternal VS, pre-conception ART, and DTG use were not associated with differences in neurodevelopment scores.
In this cohort of HEU infants, with high frequency of maternal VS and DTG use, neurodevelopment at 6 weeks was comparable to HUU infants. The mechanism underlying higher neurodevelopment scores with maternal ART duration and infant combination ART is unclear and could reflect undetected differences in infant exposure to maternal virus or other factors. Longitudinal evaluation will be useful to discern biologic and sociocultural determinants of neurodevelopment among HEU infants.
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