Mitochondrial toxicity in HIV type-1-exposed pregnancies in the era of highly active antiretroviral therapy

Antivir Ther. 2009;14(3):331-8.


Background: The aim of this study was to determine the effects of HIV type-1 (HIV-1) infection and antiretroviral therapy (ART) on placental mitochondria.

Methods: HIV-1-infected pregnant women and HIV-1-uninfected controls were enrolled prospectively. Placental mitochondrial DNA (mtDNA) copy numbers were determined by quantitative PCR, subunits II and IV of cytochrome c oxidase (COX) were quantified by western blot and mitochondrial ultrastructure was evaluated by electron microscopy. Venous blood lactate was measured in newborns.

Results: In total, 45 HIV-1-infected pregnant women on ART and 32 controls were included. Mean +/-sd mtDNA copy numbers were significantly reduced in ART and HIV-1-exposed placentas (240 +/-118 copies/cell) in comparison with controls (686 +/-842 copies/cell; P<0.001). The mean COX II/IV ratio was 48% lower in the investigational group compared with controls (P<0.001). There was no evidence of severe ultrastructural damage within mitochondria of HIV-1-infected ART-exposed placentas. Although lactate levels between newborns did not differ, they were negatively correlated with placental mtDNA levels. There was no clear association between mitochondrial parameters and a particular nucleoside reverse transcriptase inhibitor (NRTI), the number of NRTIs or time of NRTI exposure.

Conclusions: Placental tissue of HIV-1-infected ART-exposed pregnancies shows evidence of mtDNA depletion with secondary respiratory chain compromise. The clinical effects of this finding warrant further investigation.

MeSH terms

  • Adult
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active / adverse effects
  • DNA, Mitochondrial / analysis
  • Electron Transport Complex IV / metabolism
  • Female
  • HIV Infections / drug therapy*
  • HIV-1*
  • Humans
  • Infant, Newborn / blood
  • Lactic Acid / blood
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria / ultrastructure
  • Placenta / drug effects*
  • Placenta / metabolism
  • Placenta / ultrastructure
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy
  • Pregnancy Complications, Infectious / virology*
  • Retrospective Studies


  • Anti-HIV Agents
  • DNA, Mitochondrial
  • Lactic Acid
  • cytochrome C oxidase subunit II
  • Electron Transport Complex IV