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Pediatr Infect Dis J. 2019 Apr 10. doi: 10.1097/INF.0000000000002332. [Epub ahead of print]

In Utero Efavirenz Exposure and Neurodevelopmental Outcomes in HIV-exposed Uninfected Children in Botswana.

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From the Center for Neuropsychology, Department of Psychiatry, Boston Children's Hospital, Boston, Massachusetts.
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Goodtables Consulting, Norman, Oklahoma.
Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Educate Africa, Mombasa, Kenya.
Massachusetts General Hospital, Boston, Massachusetts.
Ministry of Health and Wellness, Gaborone, Botswana.
Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts.



Minimal data exist related to neurodevelopment after in utero exposure to Efavirenz (EFV). We sought to compare neurodevelopmental outcomes in HIV-exposed/uninfected (HEU) children with in utero exposure to EFV-based triple antiretroviral treatment (ART) versus non-EFV-based ART, and to examine whether timing of initial EFV exposure is associated with neurodevelopment deficits.


Women living with HIV who had received EFV-based ART during pregnancy and whose HEU newborn participated in a prior study were reconsented for their HEU toddler to undergo neurodevelopmental testing at 24 months old. We administered the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), Developmental Milestones Checklist (DMC) and Profile of Social Emotional Development (PSED). We compared outcomes to previously-collected data from a cohort of 24-month-old HEU children with in utero exposure to non-EFV-based ART. Adjusted general linear models were used to compare mean outcomes.


Our analysis included 493 HEU children (126 EFV-exposed, 367 EFV-unexposed). Adjusted mean scores for the EFV-exposed group were worse than the EFV-unexposed group on BSID-III Receptive Language (adjusted means = 21.5 vs. 22.5, P = 0.05), DMC Locomotor (30.7 vs. 32.0, P < 0.01) and Fine Motor scales (17.8 vs. 19.2, P < 0.01); and PSED (11.7 vs. 9.9, P = 0.02); but better on the DMC Language scale (17.6 vs. 16.5, P = 0.01). Earlier (vs. later) EFV exposure was associated with worse scores on the BSID-III Receptive Language scale (20.7 vs. 22.2, P = 0.02).


HEU children exposed in utero to EFV-based ART may be at higher risk for neurodevelopmental and social-emotional deficits than HEU children exposed to non-EFV-based ART.

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