Objective: To examine the impact of in utero exposure to dolutegravir (DTG)- or efavirenz (EFV)-based antiretroviral treatment (ART) on child neurodevelopmental (ND) outcomes.

Design: Prospective cohort design, enrolling 3 cohorts of 2-year-olds: children HIV-negative born to mothers with HIV (CHEU) receiving either DTG-based or EFV-based 3-drug ART during pregnancy, and children born to mothers without HIV (CHUU).

Methods: Primary child ND outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and compared between cohorts using generalized estimating equation models adjusted for confounders. Children were classified as having an "adverse ND outcome" if they scored ≥1 standard deviation (SD) below the mean or were unable to complete the BSID-III.

Results: 564 participants (202 DTG-exposed, 202 EFV-exposed, 160 HIV-unexposed; mean age 25.7 months, 49% female). Mean (SD) Gross Motor scores were slightly lower among CHEU vs. CHUU (54.6 (3.6) vs. 55.6 (4.3)) and among EFV-exposed vs. DTG-exposed (54.3 (3.5) vs. 54.9 (3.6)). CHEU were more likely to be classified as having an "adverse" expressive language outcome (13.2% vs 7.0%, aRR = 2.06 (95%CI: 1.05, 4.03)) than CHUU, but other ND outcomes were similar. DTG exposure was associated with less frequent "adverse" classification in Cognitive (2.5% vs 7.4% aRR = 0.33 (0.13, 0.79)) and Expressive Language domains (10.0% vs 16.4%, aRR = 0.58 (0.35, 0.95)), compared to EFV-exposure.

Conclusions: Two-year ND outcomes among Botswana children DTG-exposed, EFV-exposed, and HIV-unexposed were mostly comparable. Children exposed in utero to EFV-based ART had higher risk of "adverse" cognitive and expressive language outcomes compared to children DTG-exposed.