Evidence of Subclinical mtDNA Alterations in HIV-Infected Pregnant Women Receiving Combination Antiretroviral Therapy Compared to HIV-Negative Pregnant Women

PLoS One. 2015 Aug 6;10(8):e0135041. doi: 10.1371/journal.pone.0135041. eCollection 2015.

Abstract

Introduction: Combination antiretroviral therapy (cART) can effectively prevent vertical transmission of HIV but there is potential risk of adverse maternal, foetal or infant effects. Specifically, the effect of cART use during pregnancy on mitochondrial DNA (mtDNA) content in HIV-positive (HIV+) women is unclear. We sought to characterize subclinical alterations in peripheral blood mtDNA levels in cART-treated HIV+ women during pregnancy and the postpartum period.

Methods: This prospective longitudinal observational cohort study enrolled both HIV+ and HIV-negative (HIV-) pregnant women. Clinical data and blood samples were collected at three time points in pregnancy (13-<23 weeks, 23-<30 weeks, 30-40 weeks), and at delivery and six weeks post-partum in HIV+ women. Peripheral blood mtDNA to nuclear DNA (nDNA) ratio was measured by qPCR.

Results: Over a four year period, 63 HIV+ and 42 HIV- women were enrolled. HIV+ women showed significantly lower mtDNA/nDNA ratios compared to HIV- women during pregnancy (p = 0.003), after controlling for platelet count and repeated measurements using a multivariable mixed-effects model. Ethnicity, gestational age (GA) and substance use were also significantly associated with mtDNA/nDNA ratio (p≤0.02). Among HIV+ women, higher CD4 nadir was associated with higher mtDNA/nDNA ratios (p<0.0001), and these ratio were significantly lower during pregnancy compared to the postpartum period (p<0.0001).

Conclusions: In the context of this study, it was not possible to distinguish between mtDNA effects related to HIV infection versus cART therapy. Nevertheless, while mtDNA levels were relatively stable over time in both groups during pregnancy, they were significantly lower in HIV+ women compared to HIV- women. Although no immediate clinical impact was observed on maternal or infant health, lower maternal mtDNA levels may exert long-term effects on women and children and remain a concern. Improved knowledge of such subclinical alterations is another step toward optimizing the safety and efficacy of cART regimens during pregnancy.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism
  • Female
  • Gestational Age
  • HIV Infections / drug therapy*
  • HIV Infections / pathology
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / growth & development
  • Humans
  • Infant, Newborn
  • Longitudinal Studies
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Postpartum Period
  • Pregnancy
  • Pregnancy Complications, Infectious / pathology*
  • Pregnancy Complications, Infectious / virology
  • Prospective Studies

Substances

  • Anti-HIV Agents
  • DNA, Mitochondrial

Grants and funding

Financial support for this study was provided by a research grant from the Canadian Foundation for AIDS Research (CANFAR; www.canfar.com) awarded to DMM and HCFC (grant reference #016012). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.