Blood mitochondrial DNA mutations in HIV-infected women and their infants exposed to HAART during pregnancy

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
AIDS (London, England) (Impact Factor: 5.55). 03/2012; 26(6):675-83. DOI: 10.1097/QAD.0b013e32835142eb
Source: PubMed


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.
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.
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.
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.

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Available from: Evelyn J Maan, Apr 10, 2014
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    • "For example, NRTIs may accelerate aspects of intrinsic biological ageing via clonal expansion of mtDNA mutations (Payne et al., 2011). HIV and/or HAART exposure are also associated with increased prevalence of AC/TG mtDNA mutations in mothers and show a similar tendency in infants exposed during pregnancy (Jitratkosol et al., 2012). This suggests that mtDNA mutations may affect the ageing trajectories of HIV and ART-exposed populations. "
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