Cardiac effects of in-utero exposure to antiretroviral therapy in HIV-uninfected children born to HIV-infected mothers

AIDS. 2015 Jan 2;29(1):91-100. doi: 10.1097/QAD.0000000000000499.


Objectives: We evaluated the potential cardiac effects of in-utero exposures to antiretroviral drugs in HIV-exposed but uninfected (HEU) children.

Design and methods: We compared echocardiographic parameters of left ventricular function (ejection fraction, fractional shortening, and stress-velocity index) and structure (left ventricular dimension, posterior wall/septal thickness, mass, thickness-to-dimension ratio, and wall stress) (expressed as Z-scores to account for age and body surface area) between HEU and HIV-unexposed cohorts from the Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring for ART Toxicities study. Within the HEU group, we investigated the associations between the echocardiographic Z-scores and in-utero exposures to maternal antiretroviral drugs.

Results: There were no significant differences in echocardiographic Z-scores between 417 HEU and 98 HIV-unexposed children aged 2-7 years. Restricting the analysis to HEU children, first-trimester exposures to combination antiretroviral therapy (a regimen including at least three antiretroviral drugs) and to certain specific antiretroviral drugs were associated with significantly lower stress-velocity Z-scores (mean decreases of 0.22-0.40 SDs). Exposure to combination antiretroviral therapy was also associated with lower left ventricular dimension Z-scores (mean decrease of 0.44 SD). First-trimester exposure to combination antiretroviral therapy was associated with higher mean left ventricular posterior wall thickness and lower mean left ventricular wall stress Z-scores.

Conclusion: There was no evidence of significant cardiac toxicity of perinatal combination antiretroviral therapy exposure in HEU children. Subclinical differences in left ventricular structure and function with specific in-utero antiretroviral exposures indicate the need for a longitudinal cardiac study in HEU children to assess long-term cardiac risk and cardiac monitoring recommendations.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antiretroviral Therapy, Highly Active / adverse effects*
  • Child
  • Child, Preschool
  • Echocardiography
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Infectious Disease Transmission, Vertical / prevention & control
  • Male
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy
  • Pregnancy Complications, Infectious / virology
  • Prenatal Exposure Delayed Effects / epidemiology*
  • Prospective Studies
  • Ventricular Function, Left / drug effects*