Sumona Chaudhury1, Gloria K Mayondi2, Paige L Williams1,3, Jean Leidner4, Roger Shapiro5, Modiegi Diseko2, Gbolahan Ajibola2, Penny Holding6, Vicki Tepper7, Joseph Makhema2, Chipo Petlo2, George R Seage1, Shahin Lockman2,8,9, Betsy Kammerer10,11. 1. Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts, USA. 2. Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. 3. Department of Biostatistics, Harvard TH Chan School of Public Health, Boston Massachusetts. 4. Goodtables Data Consulting, Norman, Oklahoma, USA. 5. Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. 6. Independent Consultant, Nairobi, Kenya. 7. Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland. 8. Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health. 9. Infectious Disease Division, Brigham and Women's Hospital. 10. Department of Psychiatry, Children's Hospital Boston. 11. Harvard Medical School, Boston, Massachusetts, USA.
Abstract
OBJECTIVE: Conflicting data exist regarding the impact of in-utero exposure to maternal combination antiretrovirals. We compared neurodevelopmental outcomes between HIV-exposed-uninfected (HEU) children exposed in utero to three-drug combination antiretroviral therapy (ART) vs. zidovudine (ZDV) monotherapy. DESIGN: Prospective study of child neurodevelopment, nested within two cohorts of HIV-infected mothers and their children in Botswana (one observational, one interventional). METHODS: The Tshipidi and Mma Bana studies enrolled HIV-infected women during pregnancy and followed their HEU children for 24 months. Mothers took three-drug ART or ZDV during pregnancy. ART-exposed babies were mostly breastfed, and ZDV-exposed were formula-fed. Neurodevelopmental outcomes, measured at 24 months using Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) and Development Milestones Checklist (DMC), were compared in adjusted linear regression according to antiretroviral exposure. RESULTS: Of 598 HEU children with valid neurodevelopment assessments, 382 were ART-exposed and 210 were ZDV-exposed. Adjusted mean Bayley-III scores were similar among ART-exposed vs. ZDV-exposed, with adjusted mean differences (95% confidence interval): Bayley-III Cognitive: -0.3 (-1.4, 0.9); Gross Motor: 0.8 (-0.1, 1.7); Fine Motor: 0.5 (-0.2, 1.3); Expressive Language: 0.7 (-0.3, 1.7); Receptive Language: 0.1 (-0.7, 0.8); and DMC Locomotor: 0.0 (-0.5, 0.6); Fine Motor: 0.3 (-0.3, 0.8); Language: -0.1 (-0.5, 0.4); Personal-Social: 0.2 (-0.7, 1.1). Similarly, when restricted to formula-fed children in one cohort (Tshipidi), there were no differences in adjusted mean scores. CONCLUSION: Neurodevelopmental outcomes at 24 months of age were similar in ART-exposed vs. ZDV-exposed HEU children. Maternal ART with breastfeeding does not appear to have an adverse effect on neurodevelopment.
OBJECTIVE: Conflicting data exist regarding the impact of in-utero exposure to maternal combination antiretrovirals. We compared neurodevelopmental outcomes between HIV-exposed-uninfected (HEU) children exposed in utero to three-drug combination antiretroviral therapy (ART) vs. zidovudine (ZDV) monotherapy. DESIGN: Prospective study of child neurodevelopment, nested within two cohorts of HIV-infected mothers and their children in Botswana (one observational, one interventional). METHODS: The Tshipidi and Mma Bana studies enrolled HIV-infectedwomen during pregnancy and followed their HEU children for 24 months. Mothers took three-drug ART or ZDV during pregnancy. ART-exposed babies were mostly breastfed, and ZDV-exposed were formula-fed. Neurodevelopmental outcomes, measured at 24 months using Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) and Development Milestones Checklist (DMC), were compared in adjusted linear regression according to antiretroviral exposure. RESULTS: Of 598 HEU children with valid neurodevelopment assessments, 382 were ART-exposed and 210 were ZDV-exposed. Adjusted mean Bayley-III scores were similar among ART-exposed vs. ZDV-exposed, with adjusted mean differences (95% confidence interval): Bayley-III Cognitive: -0.3 (-1.4, 0.9); Gross Motor: 0.8 (-0.1, 1.7); Fine Motor: 0.5 (-0.2, 1.3); Expressive Language: 0.7 (-0.3, 1.7); Receptive Language: 0.1 (-0.7, 0.8); and DMC Locomotor: 0.0 (-0.5, 0.6); Fine Motor: 0.3 (-0.3, 0.8); Language: -0.1 (-0.5, 0.4); Personal-Social: 0.2 (-0.7, 1.1). Similarly, when restricted to formula-fed children in one cohort (Tshipidi), there were no differences in adjusted mean scores. CONCLUSION: Neurodevelopmental outcomes at 24 months of age were similar in ART-exposed vs. ZDV-exposed HEU children. Maternal ART with breastfeeding does not appear to have an adverse effect on neurodevelopment.
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