Neurodevelopmental outcomes in children exposed in utero to dolutegravir- or efavirenz-based antiretroviral treatment.

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

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

Methods: Primary child neurodevelopmental 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 at least 1 standard deviation (SD) below the mean or were unable to complete the BSID-III.

Results: Five hundred and sixty-four 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%, adjusted risk ratio (aRR) = 2.06, 95% confidence interval (CI) 1.05-4.03] than CHUU, but other neurodevelopmental outcomes were similar. DTG exposure was associated with less frequent 'adverse' classification in Cognitive (2.5 vs. 7.4%, aRR = 0.33, 95% CI 0.13-0.79) and Expressive Language domains (10.0 vs. 16.4%, aRR = 0.58, 95% CI 0.35, 0.95), compared to EFV exposure.

Conclusion: Two-year neurodevelopmental 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 with children DTG-exposed.