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


METHODS
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.


CONCLUSIONS
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.
McComsey
Grace A
GA
Case Western Reserve University, Cleveland, Ohio 44106, USA. mccomsey.grace@clevelandactu.org
Kang
Minhee
M
Ross
Allison C
AC
Lebrecht
Dirk
D
Livingston
Elizabeth
E
Melvin
Ann
A
Hitti
Jane
J
Cohn
Susan E
SE
Walker
Ulrich A
UA
D000293:Adolescent; D000328:Adult; D001724:Birth Weight; D015153:Blotting, Western; D001827:Body Height; D018791:CD4 Lymphocyte Count; D045304:Cytochromes c / Q000032:analysis; D004272:DNA, Mitochondrial / Q000032:analysis*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000737:chemistry* / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000032:analysis*; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012367:RNA, Viral; D045304:Cytochromes c