title: Hematologic and hepatic toxicities associated with antenatal and postnatal exposure to maternal highly active antiretroviral therapy among infants.
abstract: OBJECTIVE
  To assess hematologic and hepatic toxicities associated with in utero and breastfeeding exposure to maternal highly active antiretroviral therapy (HAART) among infants in Botswana.
  
  
  METHODS
  A nested cohort study within a randomized clinical trial (the Mashi Study). Laboratory toxicities among infants born to women who initiated HAART before delivery were compared with toxicities among those born to women who received zidovudine and a single dose of nevirapine or placebo in labor. Infants were randomized to breastfeed with extended zidovudine or to formula-feed.
  
  
  METHODS
  Hemoglobin concentrations, absolute neutrophil and platelet counts, and alanine aminotransferase and aspartate aminotransferase levels were recorded from birth to 7 months of age in infants. Grade 3 and 4 toxicities were compared by infant antiretroviral exposure status.
  
  
  RESULTS
  In-utero exposure to maternal HAART was associated with increased risk for neutropenia in infants up to 1 month of age; 21.7% of HAART-exposed infants were neutropenic, compared with 5.5% of the infants exposed to zidovudine (P < 0.01). However, neutropenia was no longer associated with antenatal exposure to HAART after 1 month of age. Postnatal exposure to HAART was not associated with hematologic or hepatic toxicities. Laboratory toxicities were clinically asymptomatic in all but one infant.
  
  
  CONCLUSIONS
  Exposure to maternal HAART in utero may increase the risk for infant neutropenia, particularly among breastfed infants, but the clinical significance of this finding is uncertain. The lack of association between exposure to HAART through breastfeeding and long-term toxicities in infants is reassuring but deserves study in larger cohorts.
authors.affiliation: Harvard College, Harvard Faculty of Arts and Sciences, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Woong Hwan
authors.initials: WH
authors.lastname: Bae
authors.forename: Carolyn
authors.initials: C
authors.lastname: Wester
authors.forename: Laura M
authors.initials: LM
authors.lastname: Smeaton
authors.forename: Roger L
authors.initials: RL
authors.lastname: Shapiro
authors.forename: Shahin
authors.initials: S
authors.lastname: Lockman
authors.forename: Kenneth
authors.initials: K
authors.lastname: Onyait
authors.forename: Ibou
authors.initials: I
authors.lastname: Thior
authors.forename: Max
authors.initials: M
authors.lastname: Essex
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001902:Botswana; D001942:Breast Feeding; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000635:transmission*; D015497:HIV-1; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D009503:Neutropenia / Q000209:etiology / Q000276:immunology; D019829:Nevirapine / Q000009:adverse effects / Q000627:therapeutic use; D010976:Platelet Count; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000276:immunology; D011297:Prenatal Exposure Delayed Effects; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D015415:Biomarkers; D006454:Hemoglobins; D015215:Zidovudine; D019829:Nevirapine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase