PMID- 30985518 OWN - NLM STAT- MEDLINE DCOM- 20200427 LR - 20201209 IS - 1532-0987 (Electronic) IS - 0891-3668 (Print) IS - 0891-3668 (Linking) VI - 38 IP - 8 DP - 2019 Aug TI - In Utero Efavirenz Exposure and Neurodevelopmental Outcomes in HIV-exposed Uninfected Children in Botswana. PG - 828-834 LID - 10.1097/INF.0000000000002332 [doi] AB - 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. FAU - Cassidy, Adam R AU - Cassidy AR AD - From the Center for Neuropsychology, Department of Psychiatry, Boston Children's Hospital, Boston, Massachusetts. AD - Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. FAU - Williams, Paige L AU - Williams PL AD - Harvard T. H. Chan School of Public Health, Boston, Massachusetts. FAU - Leidner, Jean AU - Leidner J AD - Goodtables Consulting, Norman, Oklahoma. FAU - Mayondi, Gloria AU - Mayondi G AD - Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. FAU - Ajibola, Gbolahan AU - Ajibola G AD - Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. FAU - Makhema, Joseph AU - Makhema J AD - Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. FAU - Holding, Penny A AU - Holding PA AD - Educate Africa, Mombasa, Kenya. FAU - Powis, Kathleen M AU - Powis KM AD - Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. AD - Harvard T. H. Chan School of Public Health, Boston, Massachusetts. AD - Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. AD - Massachusetts General Hospital, Boston, Massachusetts. FAU - Batlang, Oganne AU - Batlang O AD - Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. FAU - Petlo, Chipo AU - Petlo C AD - Ministry of Health and Wellness, Gaborone, Botswana. FAU - Shapiro, Roger AU - Shapiro R AD - From the Center for Neuropsychology, Department of Psychiatry, Boston Children's Hospital, Boston, Massachusetts. AD - Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. AD - Harvard T. H. Chan School of Public Health, Boston, Massachusetts. AD - Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts. FAU - Kammerer, Betsy AU - Kammerer B AD - From the Center for Neuropsychology, Department of Psychiatry, Boston Children's Hospital, Boston, Massachusetts. AD - Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. FAU - Lockman, Shahin AU - Lockman S AD - From the Center for Neuropsychology, Department of Psychiatry, Boston Children's Hospital, Boston, Massachusetts. AD - Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. AD - Harvard T. H. Chan School of Public Health, Boston, Massachusetts. AD - Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts. LA - eng GR - K24 AI131928/AI/NIAID NIH HHS/United States GR - P30 AI060354/AI/NIAID NIH HHS/United States GR - R01 HD061265/HD/NICHD NIH HHS/United States GR - R01 MH087344/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Pediatr Infect Dis J JT - The Pediatric infectious disease journal JID - 8701858 RN - 0 (Alkynes) RN - 0 (Benzoxazines) RN - 0 (Cyclopropanes) RN - 0 (Reverse Transcriptase Inhibitors) RN - JE6H2O27P8 (efavirenz) SB - IM MH - Alkynes MH - Benzoxazines/*adverse effects/therapeutic use MH - Botswana/epidemiology MH - Child MH - *Child Development MH - Child, Preschool MH - Cyclopropanes MH - Female MH - HIV Infections/drug therapy/*epidemiology/virology MH - Humans MH - Male MH - Outcome Assessment, Health Care MH - Paternal Exposure/*adverse effects MH - Pregnancy MH - Pregnancy Complications, Infectious/*epidemiology MH - *Prenatal Exposure Delayed Effects MH - Reverse Transcriptase Inhibitors/*adverse effects/therapeutic use PMC - PMC6629483 MID - NIHMS1523945 COIS- Conflict of Interest Disclosures: The authors have no disclosures. EDAT- 2019/04/16 06:00 MHDA- 2020/04/28 06:00 PMCR- 2020/08/01 CRDT- 2019/04/16 06:00 PHST- 2019/04/16 06:00 [pubmed] PHST- 2020/04/28 06:00 [medline] PHST- 2019/04/16 06:00 [entrez] PHST- 2020/08/01 00:00 [pmc-release] AID - 10.1097/INF.0000000000002332 [doi] PST - ppublish SO - Pediatr Infect Dis J. 2019 Aug;38(8):828-834. doi: 10.1097/INF.0000000000002332.