title: In-utero triple antiretroviral exposure associated with decreased growth among HIV-exposed uninfected infants in Botswana.
abstract: OBJECTIVE
  To assess associations between in-utero triple antiretrovirals (cART) versus zidovudine (ZDV) monotherapy exposure and growth among HIV-uninfected children of HIV-infected women in Botswana.
  
  
  METHODS
  Secondary retrospective data analysis from two randomized intervention trials of mother-to-child HIV transmission prevention.
  
  
  METHODS
  The Mashi and Mma Bana studies enrolled HIV-infected pregnant women, following their children through 24 months of age. This analysis includes singleton, full-term, HIV-exposed uninfected children. Mothers received cART or ZDV at least 2 weeks predelivery, and breastfed up to 6 months. Weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) z-scores were derived. Mean z-scores were compared by exposure group at 24 months (t-test, linear regression).
  
  
  RESULTS
  Of 819 children, 303 were ZDV- and 516 cART-exposed in utero. Maternal median enrolment CD4 was higher among ZDV versus cART-treated mothers (393 versus 324 cells/μl; P < 0.0001). Median duration of antepartum antiretroviral use was shorter among ZDV-treated women (5.7 versus 12.0 weeks; P < 0.0001). Median months breastfed were similar (5.9 and 6.0; P = 0.43). At 24 months, mean LAZ and WAZ were significantly lower among cART-exposed children (LAZ -1.01 versus -0.74; P = 0.003) (WAZ -0.53 versus -0.30; P = 0.002) in unadjusted analyses. Adjusting for maternal CD4, viral load, enrolment site and maternal anthropometric measures, cART-exposed children had significantly lower LAZ and WAZ at 24 months (P = 0.0004 for both).
  
  
  CONCLUSIONS
  At 24 months, in-utero cART-exposed children had significantly lower LAZ and WAZ. Poor growth impacts childhood and adult mortality. These findings raise concerns for potential lasting health impacts among HIV-exposed uninfected children with in-utero cART exposure.
authors.affiliation: aDepartments of Medicine and Pediatrics, Massachusetts General Hospital, Boston bDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA cBotswana Harvard AIDS Institute Partnership, Gaborone, Botswana dDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA eElizabeth Glaser Pediatric AIDS Foundation, Harare, Zimbabwe fFaculty of Medicine, University of Botswana, Gabarone, Botswana gDivisions of Infectious Diseases and General Medicine, Department of Obstetrics, Gynecology, and Reproductive Science, Icahn School of Medicine, Mount Sinai, New York City, New York, USA hDepartment of Epidemiology, Harvard T.H. Chan School of Public Health iInfectious Disease Division, Brigham and Women's Hospital, Boston jDepartments of Global Health and Population, Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health kBeth Israel Deaconess Medical Center, Infectious Diseases Department, Boston, Massachusetts, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Powis
authors.forename: Laura
authors.initials: L
authors.lastname: Smeaton
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hughes
authors.forename: Esther A
authors.initials: EA
authors.lastname: Tumbare
authors.forename: Sajini
authors.initials: S
authors.lastname: Souda
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jao
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Wirth
authors.forename: Joseph
authors.initials: J
authors.lastname: Makhema
authors.forename: Shahin
authors.initials: S
authors.lastname: Lockman
authors.forename: Wafaie
authors.initials: W
authors.lastname: Fawzi
authors.forename: Max
authors.initials: M
authors.lastname: Essex
authors.forename: Roger L
authors.initials: RL
authors.lastname: Shapiro
mesh_terms: D000328:Adult; D000886:Anthropometry; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001827:Body Height; D001835:Body Weight; D001902:Botswana / Q000453:epidemiology; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents