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.