Placenta and umbilical cord blood were obtained at delivery and infant blood was obtained within 48 h of delivery. mtDNA content was determined for each specimen. Nuclear [subunit IV of cytochrome c-oxidase 3-Methyladenine (COX IV)]- and mitochondrial (COX II)-encoded polypeptides of the oxidative phosphorylation enzyme cytochrome c-oxidase were quantified in cord and infant blood. Placental mitochondria malondialdehyde (MDA) concentrations were measured as a marker of oxidative

stress. Twenty HIV-positive/HIV-exposed and 26 control mother–infant pairs were enrolled in the study. All HIV-infected women and their infants received ART. Placental MDA concentration and mtDNA content in placenta and cord blood were similar between groups. The

cord blood COX II:IV ratio was lower in the HIV-positive group than in the controls, whereas the infant peripheral blood mtDNA content was higher in the HIV-exposed infants, but the infant peripheral blood COX II:IV ratio was similar. Crizotinib price No infant had clinical evidence of mitochondrial disease or acquired HIV infection. In multivariable regression analyses, the significant findings in cord and infant blood were both most associated with HIV/ART exposure. HIV-exposed infants showed reduced umbilical cord blood mitochondrial enzyme expression with increased infant peripheral blood mitochondrial DNA levels, the latter possibly reflecting a compensatory mechanism to overcome HIV/ART-associated mitochondrial toxicity. Strategies implemented for HIV-infected pregnant women and HIV-exposed infants, especially combination antiretroviral therapy (ART) given to women during pregnancy, have dramatically decreased the risk of mother-to-child transmission (MTCT) [1]. The vast majority of infants

do not exhibit any clinically apparent toxicity associated with this in utero ART exposure, and therefore learn more the benefit of reduced MTCT far outweighs the possible detrimental effects in the infant. However, there is still uncertainty about deleterious mitochondrial effects in ART-exposed infants, based on a number of previous animal and human studies [2–10]. The first report in 1999 from Blanche et al. detailed eight cases of perinatally nucleoside reverse transcriptase inhibitor (NRTI)-exposed, noninfected children with hyperlactataemia who exhibited neurological and developmental sequelae consistent with mitochondrial dysfunction [4]. The same group of investigators also described 12 perinatally NRTI-exposed children in a cohort of 2644 with motor abnormalities, seizures, and cognitive developmental delays, which were often associated with abnormal magnetic resonance imaging (MRI) results and/or significant hyperlactataemia [5]. The 18-month incidence for mitochondrial dysfunction was 0.26% in these ART-exposed children, compared with 0.01% for paediatric neuro-mitochondrial diseases in the general population.