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

Cassidy, Adam R. PhD*,†; Williams, Paige L. PhD; Leidner, Jean MSc§; Mayondi, Gloria BS; Ajibola, Gbolahan MBBS; Makhema, Joseph MBChB, FRCP; Holding, Penny A. PhD; Powis, Kathleen M. MD†,‡,¶,**; Batlang, Oganne BNSc; Petlo, Chipo BEd††; Shapiro, Roger MD*,†,‡,‡‡; Kammerer, Betsy PhD*,†; Lockman, Shahin MD*,†,‡,§§

The Pediatric Infectious Disease Journal: August 2019 - Volume 38 - Issue 8 - p 828–834
doi: 10.1097/INF.0000000000002332
HIV Reports

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

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.

Accepted for publication February 10, 2019.

This research was supported by a Scholar Award grant from the Harvard University Center for AIDS Research (HU CFAR NIH/NIAID fund 5P30AI060354-12), and by R01 MH087344, R01 HD061265 and K24 AI131928.

The authors have no conflicts of interest to disclose

All authors contributed significantly to the manuscript.

The study sponsor did not have any role in the study design; collection, analysis, interpretation of data; writing of the manuscript; or the decision to submit the manuscript for publication.

Address for correspondence: Adam R. Cassidy, PhD, ABPP, Center for Neuropsychology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115. E-mail:

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