Increased mtDNA levels without change in mitochondrial enzymes in peripheral blood mononuclear cells of infants born to HIV-infected mothers on antiretroviral therapy

HIV Clin Trials. Mar-Apr 2008;9(2):126-36. doi: 10.1310/hct0902-126.

Abstract

Background: The effects of gestational nucleoside reverse transcriptase inhibitors (NRTIs) on mitochondrial DNA (mtDNA) are controversial. The effects of mtDNA depletion on mitochondrial function have not been assessed.

Method: In peripheral blood mononuclear cells (PBMCs) from infants born to HIV-infected women and infants born to HIV-1-uninfected women, mtDNA copy numbers were determined by quantitative PCR; nuclear (COXIV)- and mitochondrial (COXII)-encoded polypeptides of the oxidative phosphorylation enzyme cytochrome c-oxidase (COX or complex IV) were quantified by Western blot.

Results: Overall, 86 infants born to HIV-infected women and 50 controls were studied. HIV-infected mothers had a median CD4 count of 506 cells/microL; 59% had HIV RNA 50 copies/mL. No infant had clinical evidence of mitochondrial disease. The birth weight was lower (p = .016) and the body length higher (p = .002) in the HIV-exposed newborns. Eighty-one HIV-infected women had received gestational NRTIs (median duration 162 days). Median mtDNA copies/PBMC in the HIV-exposed infants were 505 (range, 120-1365) vs. 213 (27-426) in controls (p < .001). COX II/IV ratios were similar in both groups. Although mtDNA levels correlated inversely with maternal lactate, mitochondrial indices did not correlate with maternal CD4+ count, HIV RNA, smoking, or alcohol consumption.

Conclusion: We found elevated mtDNA copy numbers in PBMC of infants born to HIV-infected women, the majority of whom received NRTI-based therapy, when compared to those born to healthy HIV-negative controls, but there was no difference in mtDNA-encoded respiratory chain protein. The clinical consequence of these findings is unknown and requires further investigations.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Birth Weight
  • Blotting, Western
  • Body Height
  • CD4 Lymphocyte Count
  • Cytochromes c / analysis
  • DNA, Mitochondrial / analysis*
  • Female
  • HIV Infections / drug therapy*
  • HIV-1 / isolation & purification
  • Humans
  • Infant, Newborn
  • Leukocytes, Mononuclear / chemistry*
  • Leukocytes, Mononuclear / enzymology*
  • Mitochondrial Proteins / analysis*
  • Polymerase Chain Reaction / methods
  • Pregnancy
  • Pregnancy Complications, Infectious* / drug therapy
  • RNA, Viral / blood
  • Viral Load

Substances

  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • RNA, Viral
  • Cytochromes c

Grant support