Brain Structure of South African Children Born to Mothers on Dolutegravir Versus Efavirenz-Based Antiretroviral Therapy

Background: The 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) vs efavirenz (EFV) exposure. 

Methods: DolPHIN-2 was a randomized trial of pregnant women initiating DTG- vs 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 (CHU) children, 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. 

Results: This 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. Significant differences in global or regional brain volumes, cortical thickness, or surface area were not detected between DTG- and EFV-exposed children or between CHEU and CHU. 

Conclusion: Among this small sample of children at 3-4 years, statistically significant differences in global or regional brain structure were not detected between those exposed in the third trimester of pregnancy to DTG or EFV and CHU. Given the modest sample size, the study had limited power to detect small-to-moderate differences. 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.