Perinatal Exposure to Antiretroviral Therapy Is Associated with Increased Blood Mitochondrial DNA Levels and Decreased Mitochondrial Gene Expression in Infants

Background. The effects of perinatal antiretroviral therapy (ART) on infant mitochondrial function are not well known. We compared blood mitochondrial DNA (mtDNA) levels and mtDNA gene expression (mtRNA) in human immunodeficiency virus (HIV)–uninfected, ART-exposed infants born to HIV-positive mothers with mtDNA levels and mtDNA gene expression in control infants born to uninfected women. Methods. In this prospective cohort study, longitudinalmtDNA:nuclear DNA andmtRNA:-actinmRNA ratios were compared in blood samples obtained at various time points frombirth to 8months, using generalized estimating equation linear regression models. Results. Log10 mtDNA levels at birth were higher in ART-exposed infants, compared with levels in control infants, although the difference did not reach statistical significance (P .07 for comparison of samples obtained 0–3 days after birth). ART-exposed infants ’ mtDNA levels increased further during the zidovudine prophylaxis period— from age 4 days to age 6 weeks—(P .001) and remained significantly higher than the levels observed in control infants until the end of the study. In contrast, log10 mtRNA levels at birth were lower in ART-exposed infants than in control infants (P .03), but were not statistically different later. Conclusions. When control infants and ART-exposed infants were compared, the mtDNA level was increased but mitochondrial gene expression was decreased in ART-exposed infants. These differences persisted after zidovu