PBMC, peripheral blood mononuclear cell. == Peripheral infant blood analyses ENOblock (AP-III-a4) == In contrast to the umbilical cord blood, the mtDNA content in the peripheral infant blood was significantly increased in the HIV-exposed group compared with the controls. (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. == Results == Twenty HIV-positive/HIV-exposed and 26 control motherinfant 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 comparable 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 ENOblock (AP-III-a4) ratio was comparable. No infant had clinical evidence of mitochondrial disease or acquired HIV contamination. In multivariable regression analyses, the significant findings in cord and infant blood were both most associated with HIV/ART exposure. == Conclusions == 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. Keywords:antiretroviral brokers, HIV infection, infants, mitochondrial DNA, toxicity, vertical transmission == Introduction == 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 thisin uteroART exposure, and therefore 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 ENOblock (AP-III-a4) animal and human studies [210]. The first report in 1999 from Blancheet al. detailed eight cases of perinatally nucleoside reverse transcriptase ENOblock (AP-III-a4) inhibitor (NRTI)-uncovered, 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. In addition, 20 cases of possible mitochondrial toxicity were reported among 1037 infants given birth to to HIV-infected mothers within the Pediatric AIDS Clinical Trials Group [6]. Given the disturbing reports that depict a small percentage of ART- and HIV-exposed infants with clinically apparent disease suggestive of mitochondrial toxicity, investigators have attempted to describe the changes that occur at a cellular and/or mitochondrial DNA (mtDNA) level. For example, a small study that analysed mitochondrial ultra-structure by electron microscopy exhibited mitochondrial damage in six out of nine NRTI-exposed children compared with none out of seven infants given birth to to HIV-uninfected women [7]. Similarly, 11 of the 12 children with clinically apparent mitochondrial disease described above showed profound deficits in one of the respiratory chain complexes and/or common histological patterns of mitochondrial dysfunction [5]. Those studies that have examined mtDNA content in placenta, umbilical cord blood mononuclear cells (CBMCs), or infant peripheral blood mononuclear cells (PBMCs) in HIV- and ART-exposed asymptomatic infants compared with HIV- and ART-unexposed infants have produced conflicting results. Some studies showed mtDNA depletion [710], while others showed no change [5,11], or an increased content [12,13] compared with controls. Unfortunately, most of the previously published studies did not concurrently evaluate how observed changes in mtDNA content affected mitochondrial enzyme KITH_HHV1 antibody expression as an indirect marker of mitochondrial function and vice versa, or they investigated mtDNA content in only one or two areas at a ENOblock (AP-III-a4) time (e.g. placenta, umbilical cord blood or infant peripheral blood). Therefore, it has been difficult to compare results from one study to another, or to elucidate the origin of the damage. Thus, the purpose of this study was to more thoroughly study the effects of HIV and ART exposure in HIV-uninfected infants and to investigate increased placental oxidative stress as a possible mechanism of the mtDNA damage observed in the infants, which has not been previously explored. Our objectives were.