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

TitleIncreased mtDNA levels without change in mitochondrial enzymes in peripheral blood mononuclear cells of infants born to HIV-infected mothers on antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2008
AuthorsMcComsey GA, Kang M, Ross AC, Lebrecht D, Livingston E, Melvin A, Hitti J, Cohn SE, Walker UA
Corporate AuthorsAIDS Clinical Trials Group A5084
JournalHIV Clin Trials
Volume9
Issue2
Pagination126-36
Date Published2008 Mar-Apr
ISSN1528-4336
KeywordsAdolescent, Adult, Birth Weight, Blotting, Western, Body Height, CD4 Lymphocyte Count, Cytochromes c, DNA, Mitochondrial, Female, HIV Infections, HIV-1, Humans, Infant, Newborn, Leukocytes, Mononuclear, Mitochondrial Proteins, Polymerase Chain Reaction, Pregnancy, Pregnancy Complications, Infectious, RNA, Viral, Viral Load
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.

DOI10.1310/hct0902-126
Alternate JournalHIV Clin Trials
PubMed ID18474497
PubMed Central IDPMC3895476
Grant ListAI068636 / AI / NIAID NIH HHS / United States
AI25859 / AI / NIAID NIH HHS / United States
AI25879 / AI / NIAID NIH HHS / United States
AI25883 / AI / NIAID NIH HHS / United States
AI25897 / AI / NIAID NIH HHS / United States
AI25903 / AI / NIAID NIH HHS / United States
AI25915 / AI / NIAID NIH HHS / United States
AI27661 / AI / NIAID NIH HHS / United States
AI27664 / AI / NIAID NIH HHS / United States
AI27665 / AI / NIAID NIH HHS / United States
AI32907 / AI / NIAID NIH HHS / United States
AI34853 / AI / NIAID NIH HHS / United States
AI36219 / AI / NIAID NIH HHS / United States
AI38558 / AI / NIAID NIH HHS / United States
AI42845 / AI / NIAID NIH HHS / United States
P30 AI036219 / AI / NIAID NIH HHS / United States
RR000080 / RR / NCRR NIH HHS / United States
RR00043 / RR / NCRR NIH HHS / United States
RR00044 / RR / NCRR NIH HHS / United States
RR00069 / RR / NCRR NIH HHS / United States
RR00096 / RR / NCRR NIH HHS / United States
U01 AI038858 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI069501 / AI / NIAID NIH HHS / United States
U01 AI069501 / AI / NIAID NIH HHS / United States