Brain structure of South African children born to mothers on dolutegravir versus efavirenz-based ART

BackgroundThe impact of in utero exposure to specific antiretroviral therapy (ART), particularly integrase strand transfer inhibitors, on early brain development remains poorly understood. We used magnetic resonance imaging (MRI) to compare brain structure in children who are HIV-exposed and uninfected (CHEU) with prenatal dolutegravir (DTG) versus efavirenz (EFV) exposure MethodsDolPHIN-2 was a randomized trial of pregnant women initiating DTG-versus EFV-based ART in the third trimester. At 3-4 years of age, a subgroup of their children from the South African cohort, along with HIV-unexposed children (CHU), underwent T1-weighted MRI (DolPHIN-2 PLUS). Measurements of brain structure including volume, cortical thickness, and surface area were extracted using Freesurfer. Associations between ART /HIV exposure and child brain structure were examined using multiple linear regression. ResultsThis analysis included 58 children (25 CHEU [13 DTG, 12 EFV] and 33 CHU, mean age 46.35 months, 51.7% male). Demographic characteristics were similar across groups. No significant differences in global or regional brain volumes, cortical thickness, or surface area were observed between DTG- and EFV-exposed children or between CHEU and CHU. ConclusionAmong children exposed to ART in the third trimester, brain structural measures at 3-4 years were comparable between DTG and EFV exposure. CHEU also showed similar brain development to CHU. Further longitudinal studies with larger sample sizes are needed to assess the effects of specific ART in the context of new regimens and better maternal HIV disease control, on CHEU brain structure.