title: Decreased Mitochondrial Function Among Healthy Infants Exposed to Antiretrovirals During Gestation, Delivery and the Neonatal Period.
abstract: BACKGROUND
  Antiretroviral (ARV)-associated mitochondrial toxicity in HIV/ARV-exposed healthy infants is a concern. Clinically relevant toxicity is rare. Hyperlactatemia is common but nonspecific, both increased and decreased mitochondrial DNA (mtDNA) level has been reported. Mitochondrial function has scarcely been investigated.
  
  
  METHODS
  In a prospective observational study of 133 HIV/ARV-exposed infants, mtDNA content was measured with quantitative real-time polymerase chain reaction, and mitochondrial respiratory chain enzymatic activity of complex IV (CIV) and mitochondrial mass (MM) were assessed spectrophotometrically from cryopreserved peripheral blood mononuclear cells obtained at 6 weeks and 3, 6 and 12 months of age and compared with a control group.
  
  
  RESULTS
  Most mothers (88%) received combined ARV therapy during pregnancy, and 92% of infants received zidovudine monotherapy. No infant had clinical evidence of mitochondrial disease during follow-up. Nonsignificant higher MM and lower mtDNA levels (normalized by MM) were observed over time in HIV/ARV-exposed infants. MM-normalized CIV activity was consistently lower in HIV/ARV-exposed children than in controls over time (0.09 vs. 0.35, 0.12 vs. 0.38, 0.13 vs. 0.24 and 0.14 vs. 0.24 nmol/min/mg at 6 weeks and 3, 6 and 12 months; P = 0.014, P < 0.0001, P = 0.065 and P = 0.011, respectively) and showed a linear trend toward normalization with age (P < 0.01). In HIV/ARV-exposed infants, an inverse correlation between CIV activity and mtDNA levels was observed until 6 months of age (r = -0.327, P = 0.016; r = -0.311, P = 0.040 and r = -0.275, P = 0.046).
  
  
  CONCLUSIONS
  Mitochondrial-encoded CIV activity was consistently lower among HIV/ARV-exposed healthy infants and inversely correlated with mtDNA levels, suggesting upregulation of the latter.
authors.affiliation: From the *Infectious Diseases Unit, Pediatrics Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain; †Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; ‡Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain; §Fondo Europeo de Desarrollo Regional (FEDER), Spain; and ¶Blanquerna School of Health Science, Universitat Ramon Llull, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Noguera-Julian
authors.forename: Constanza
authors.initials: C
authors.lastname: Morén
authors.forename: Núria
authors.initials: N
authors.lastname: Rovira
authors.forename: Glòria
authors.initials: G
authors.lastname: Garrabou
authors.forename: Marc
authors.initials: M
authors.lastname: Catalán
authors.forename: Emília
authors.initials: E
authors.lastname: Sánchez
authors.forename: Francesc
authors.initials: F
authors.lastname: Cardellach
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Miró
authors.forename: Clàudia
authors.initials: C
authors.lastname: Fortuny
mesh_terms: D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004272:DNA, Mitochondrial / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011446:Prospective Studies
chemical_list: D044966:Anti-Retroviral Agents; D004272:DNA, Mitochondrial