title: Blood mitochondrial DNA mutations in HIV-infected women and their infants exposed to HAART during pregnancy.
abstract: OBJECTIVE
  Nucleo(s/t)ide reverse transcriptase inhibitors given to HIV-infected pregnant women to prevent vertical transmission may adversely affect mitochondrial DNA (mtDNA). We hypothesized that HAART-exposed/HIV-uninfected infants may show higher blood mtDNA mutation burden than controls born to HIV-uninfected mothers.
  
  
  METHODS
  Blood was collected from in-utero HIV/HAART-exposed infants and controls, as well as from a subset of their mothers. The presence of mtDNA A→C/T→G (AC/TG) mutations was measured by cloning and sequencing D-loop PCR amplicons. Relationships with maternal characteristics were examined.
  
  
  RESULTS
  No significant difference was found between the percentage of HIV/HAART-exposed infants with AC/TG mutations (N = 15/57, 26.3%) and controls (N = 10/70, 14.3%) before (P = 0.090) or after controlling for covariates (P = 0.058), although a tendency was observed. However, significantly more HIV/HAART-exposed mothers (N = 18/42, 42.9%) harboured AC/TG mutations compared with controls (N = 7/39, 17.9%) before (P = 0.015) and after (P = 0.012) controlling for covariates. AC/TG mutations were more prevalent in HIV/HAART-exposed mothers than in their infants (N = 42, 42.9 vs. 23.8%, P = 0.033), however, this difference disappeared after controlling for covariates. No difference was seen between control mothers and their infants (N = 39, both 17.9%). In HIV/HAART-exposed mothers, only a detectable HIV plasma viral load near delivery predicted AC/TG mutations.
  
  
  CONCLUSIONS
  Our results suggest that HIV and/or HAART exposure are associated with increased prevalence of AC/TG mtDNA mutations in mothers and show a similar tendency in infants exposed during pregnancy. As accumulation of mtDNA mutations has been linked with aging and age-associated diseases, this may raise concerns in the long term for HIV and HAART-exposed populations.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Marissa H J
authors.initials: MH
authors.lastname: Jitratkosol
authors.forename: Beheroze
authors.initials: B
authors.lastname: Sattha
authors.forename: Evelyn J
authors.initials: EJ
authors.lastname: Maan
authors.forename: Izabelle
authors.initials: I
authors.lastname: Gadawski
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
authors.forename: John C
authors.initials: JC
authors.lastname: Forbes
authors.forename: Ariane
authors.initials: A
authors.lastname: Alimenti
authors.forename: Julie
authors.initials: J
authors.lastname: van Schalkwyk
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Money
authors.forename: Hélène C F
authors.initials: HC
authors.lastname: Côté
mesh_terms: D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000097:blood / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008297:Male; D009154:Mutation / Q000235:genetics*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000235:genetics*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors