Neurodevelopment In HEU Children Exposed In Utero To Dolutegravir Or Efavirenz

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PROJECT SUMMARY The global population of HIV-uninfected children born following in utero exposure to HIV and ART has grown to ~15 million, with more than 1 million HIV-exposed/uninfected (HEU) babies born each year. With increased rates of early-childhood mortality and a range of medical morbidities, HEU children comprise a vulnerable population. Of particular concern is the lack of neurodevelopmental and social-emotional outcomes data following in utero exposure to some of the most commonly- used maternal ARV regimens. Efavirenz (EFV) is one of the most widely-used ARVs worldwide, including among women who are pregnant or may become pregnant. Many HIV programs are currently rolling out dolutegravir (DTG) for use in first-line ART, despite the recent early signal for neural tube defects with DTG from conception. However, no studies have evaluated whether in utero exposure to DTG-based ART poses an independent threat to neurodevelopmental and/or social- emotional outcomes in HEU children, and minimal data exist for EFV (or from older children). Our aims are thus as follows: Aim 1: To assess and compare developmental outcomes (neurodevelopment, psychosocial) at 2 years of age in HEU children exposed in utero to DTG-based ARV vs. EFV-based ART; and to compare outcomes between HEU children in each of these ARV exposure groups vs. HIV-unexposed toddlers. Aim 2: To undertake the same comparisons of ND and social-emotional outcomes as in Aim 1, but at 5 years of age, and with additional targeted assessment in these school-age children of domains that are more predictive of future functioning (e.g., executive function). Aim 3: To assess (over time) and compare depression, anxiety, and sleep problem scores in women taking DTG-based ART vs. EFV-based ART (and women living with HIV vs. HIV-negative women).