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In Utero Antiretroviral Exposure and Risk of Neurodevelopmental Problems in HIV-Exposed Uninfected 5-Year-Old

Tzy-Jyun Yao1,2, Kathleen Malee3,2, Joel Zhang1,2

  • 1Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

AIDS Patient Care and Stds
|February 24, 2023
PubMed

Insights

Antiretroviral therapy (ART) exposure during pregnancy may impact neurodevelopment in HIV-exposed but uninfected children. Atazanavir (ATV) use in later pregnancy was linked to higher risks of developmental problems in children aged five.

Area of Science:

  • Pediatric HIV/AIDS research
  • Neurodevelopmental disorders
  • Pharmacovigilance in pregnancy

Background:

  • Children perinatally HIV-exposed but uninfected (CHEU) can experience neurodevelopmental (ND) challenges.
  • In utero antiretroviral (ARV) exposure is a potential factor, but specific ARV links remain unclear.
  • Atazanavir (ATV) boosted with ritonavir is a common ARV for pregnant women, with some prior reports linking it to ND issues in CHEU.

Purpose of the Study:

  • To evaluate the association between in utero ARV exposure, specifically Atazanavir (ATV), and neurodevelopmental outcomes in 5-year-old children perinatally HIV-exposed but uninfected (CHEU).
  • To investigate the impact of the timing of ARV initiation during pregnancy on these neurodevelopmental outcomes.

Main Methods:

  • The study analyzed 5-year-old CHEU from the PHACS SMARTT study.
  • Neurodevelopment was assessed using standardized tests including the Behavior Assessment System for Children, Wechsler Preschool and Primary Scales of Intelligence, and Test of Language Development-Primary.
  • Risk for neurodevelopmental signals (≥1.5 SD below norms) was analyzed using proportional odds models, stratified by timing of ARV initiation.

Main Results:

  • Among children exposed to ARVs at conception, Atazanavir (ATV) exposure was not associated with increased risk of neurodevelopmental signals.
  • However, among children whose mothers initiated ARVs during pregnancy, ATV exposure was associated with a higher risk of neurodevelopmental signals (cOR=1.70).
  • The specific regimen of tenofovir/emtricitabine/ATV was linked to a significantly higher risk (cOR=2.31) compared to non-ATV regimens.

Conclusions:

  • The timing of in utero antiretroviral (ARV) exposure is critical in assessing neurodevelopmental risks for HIV-exposed but uninfected (CHEU) children.
  • While early ARV exposure showed no ATV-related risk, later pregnancy exposure to Atazanavir (ATV) was associated with increased neurodevelopmental challenges.
  • Continued monitoring and investigation into specific ARV impacts and exposure timing are essential for CHEU neurodevelopmental care.

Keywords:
antiretroviralconcomitant neurodevelopmental problemsprenatalpreschool

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