title: Study of oxidative, enzymatic mitochondrial respiratory chain function and apoptosis in perinatally HIV-infected pediatric patients.
abstract: Mitochondrial toxicity in perinatally human immunodeficiency virus (HIV)-infected pediatric patients has been scarcely investigated. Limited data are available about HIV or antiretroviral (ARV)-mediated mitochondrial damage in this population group, specifically, regarding oxygen consumption and apoptosis approach. We aimed to elucidate whether a given mitochondrial DNA depletion is reflected at downstream levels, to gain insight on the pathology of HIV and highly active antiretroviral therapy (HAART) in perinatally HIV-infected pediatric patients. We studied 10 healthy control participants and 20 perinatally HIV-infected pediatric patients (10 under ARV treatment and 10 off treatment). We determined mitochondrial mass, subunits II and IV of complex IV, global and specific mitochondrial enzymatic and oxidative activities, and apoptosis from peripheral blood mononuclear cells. Global oxygen consumption was significantly compromised in HIV-infected untreated patients, compared to the control group (0.76 ± 0.01 versus 1.59 ± 0.15; P = 0.014). Apoptosis showed a trend to increase in untreated patients as well. The overall complex (C) CI-III-IV activity of the mitochondrial respiratory chain (MRC) was significantly decreased in HIV-infected treated patients with respect to the control group (1.52 ± 0.38 versus 6.38 ± 1.53; P = 0.02). No statistically significant differences were found between untreated and HAART-treated patients. These findings suggest the pathogenic role of both HIV and HAART in mitochondrial dysfunction in vertical infection. The abnormalities in mitochondrial genome may be downstream reflected through a global alteration of the MRC. Mitochondrial impairment associated with HIV and HAART was generalized, rather than localized, in this series of perinatally HIV-infected patients.
authors.affiliation: Mitochondrial Functionalism Laboratory, University of Barcelona, IDIBAPS, Hospital Clínic of Barcelona, Barcelona, Spain. cmoren1@clinic.ub.es
authors.forename: Constanza
authors.initials: C
authors.lastname: Morén
authors.forename: Glòria
authors.initials: G
authors.lastname: Garrabou
authors.forename: Antoni
authors.initials: A
authors.lastname: Noguera-Julian
authors.forename: Núria
authors.initials: N
authors.lastname: Rovira
authors.forename: Marc
authors.initials: M
authors.lastname: Catalán
authors.forename: Sandra
authors.initials: S
authors.lastname: Hernández
authors.forename: Ester
authors.initials: E
authors.lastname: Tobías
authors.forename: Francesc
authors.initials: F
authors.lastname: Cardellach
authors.forename: Clàudia
authors.initials: C
authors.lastname: Fortuny
authors.forename: Òscar
authors.initials: Ò
authors.lastname: Miró
mesh_terms: D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D017209:Apoptosis / Q000502:physiology*; D002648:Child; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003430:Cross-Sectional Studies; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology*; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000502:physiology; D013030:Spain; D013053:Spectrophotometry; D018709:Statistics, Nonparametric
chemical_list: D002950:Citrate (si)-Synthase