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

Grace A. McComsey, Minhee Kang, Allison C. Ross, Dirk Lebrecht, Elizabeth Livingston, Ann Melvin, Jane Hitti, Susan E. Cohn, Ulrich A. Walker

Research output: Contribution to journalArticle

25 Scopus citations

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/μL; 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.

Original languageEnglish (US)
Pages (from-to)126-136
Number of pages11
JournalHIV Clinical Trials
Volume9
Issue number2
DOIs
StatePublished - Mar 2008

Keywords

  • Mitochondrial DNA
  • Mitochondrial enzymes
  • Mitochondrial toxicity

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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