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Possible mitochondrial dysfunction and its association with antiretroviral therapy use in children perinatally

Marilyn J Crain1, Miriam C Chernoff, James M Oleske

  • 1University of Alabama School of Medicine, Birmingham, AL 35233, USA. mcrain@peds.uab.edu

The Journal of Infectious Diseases
|June 11, 2010
PubMed

Insights

Mitochondrial dysfunction is common in children with perinatal HIV infection, particularly with certain antiretroviral drugs like stavudine and lamivudine. These findings highlight potential drug toxicities requiring further investigation.

Area of Science:

  • Pediatric infectious diseases
  • Pharmacology
  • Mitochondrial medicine

Background:

  • Mitochondrial dysfunction is linked to HIV infection and antiretroviral therapy (ART).
  • Limited research exists on mitochondrial dysfunction in children with perinatal HIV.
  • This study aimed to determine the incidence of clinically defined mitochondrial dysfunction in this population.

Purpose of the Study:

  • To estimate the incidence of clinically defined mitochondrial dysfunction in children with perinatal HIV infection.
  • To investigate the association between nucleoside reverse-transcriptase inhibitor (NRTI) use and mitochondrial dysfunction.

Main Methods:

  • Prospective cohort study (Pediatric AIDS Clinical Trials Group protocols 219 and 219C) from 1993-2004.
  • Utilized two clinical case definitions for mitochondrial dysfunction.
  • Logistic regression analyzed associations between NRTI use and mitochondrial dysfunction.

Main Results:

  • 33.5% of 2931 children met criteria for possible mitochondrial dysfunction.
  • Mortality was highest (20%) in children meeting both case definitions.
  • Stavudine use (OR, 3.44) and stavudine-didanosine (OR, 2.23) increased risk; lamivudine and lamivudine-stavudine also associated with increased risk.

Conclusions:

  • Nucleoside reverse-transcriptase inhibitor (NRTI) use, particularly stavudine and lamivudine, is associated with mitochondrial dysfunction in children with perinatal HIV.
  • Further research is needed to understand the mechanisms of NRTI-related mitochondrial toxicities.
Abstract

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