Drug Safety

, Volume 30, Issue 10, pp 845–859

Mitochondrial Disorders among Infants Exposed to HIV and Antiretroviral Therapy

  • Michele Jonsson Funk
  • Suzanne E. Belinson
  • Jeanne M. Pimenta
  • Megan Morsheimer
  • David C. Gibbons
Review Article


Although antiretroviral therapy (ART) is critical for preventing mother-to-child transmission of HIV, concern has been raised about the possibility that it may cause mitochondrial dysfunction in infants. There is adequate evidence for a mechanism by which exposure to nucleoside reverse transcriptase inhibitors (NRTIs) could lead to mitochondrial dysfunction; animal studies have shown evidence of mitochondrial dysfunction in the offspring of animals treated with NRTIs and mitochondrial disorders occur in adults treated with NRTIs. This systematic review synthesises the published research on mitochondrial dysfunction and disorders in infants exposed to HIV and antiretrovirals.

We found conflicting evidence regarding the possible association of in utero ART exposure with mortality and morbidity due to mitochondrial dysfunction. ART exposure in utero or postpartum was associated with persistent decreases in lymphocytes, neutrophils and platelets as well as an increased risk of transient lactic acidaemia, anaemia and mitochondrial DNA depletion, although these laboratory findings were generally not associated with clinical symptoms.

We conclude that large, prospective studies of HIV-exposed infants are needed to resolve the discrepant results regarding morbidity and mortality related to mitochondrial disorders, to ascertain the clinical significance of effects on laboratory values, to determine whether or not the incidence of mitochondrial disorders differs by regimen and to develop predictive models that might identify which infants are at the greatest risk. The challenges that remain to be addressed include the development of a sensitive but affordable screening algorithm in combination with specific diagnostic criteria; consistent collection of data on ART exposure and other risk factors, long-term follow-up of HIV-exposed but uninfected children and implementation in resource-limited settings.

Supplementary material

40264_2012_30100845_MOESM1_ESM.pdf (150 kb)
Supplementary material, approximately 153 KB.


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Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • Michele Jonsson Funk
    • 1
  • Suzanne E. Belinson
    • 1
    • 2
  • Jeanne M. Pimenta
    • 3
  • Megan Morsheimer
    • 2
  • David C. Gibbons
    • 4
  1. 1.Department of Epidemiology, CB#7521University of North CarolinaChapel HillUSA
  2. 2.Worldwide Epidemiology, GlaxoSmithKline Research & DevelopmentResearch Triangle ParkUSA
  3. 3.Worldwide Epidemiology, GlaxoSmithKline Research & DevelopmentGreenfordUK
  4. 4.Medicines Development, GlaxoSmithKline Research & DevelopmentKing of PrussiaUSA

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