Cardiac and mitochondrial function in HIV-uninfected fetuses exposed to antiretroviral treatment

PLoS One. 2019 Mar 4;14(3):e0213279. doi: 10.1371/journal.pone.0213279. eCollection 2019.

Abstract

Background: Mitochondrial toxicity related to maternal combined antiretroviral treatment (cART) may have an impact on the heart of HIV-exposed uninfected (HEU) fetuses. Our objective was to evaluate fetal cardiovascular and mitochondrial biomarkers in HIV pregnancies.

Methods: Prospective cohort including 47 HIV-infected and 47 non HIV-infected pregnancies. Fetal echocardiography was performed at 26-32 weeks of pregnancy. Umbilical cord blood and placental tissue were collected to study mitochondrial DNA content (mtDNA) (ratio 12SrRNA/RNAseP) and mitochondrial function (cytochrome c oxidase, COX, enzymatic activity) normalized by mitochondrial content (citrate synthase, CS).

Results: HEU fetuses showed hypertrophic hearts (left myocardial wall thickness: HIV mean 3.21 mm (SD 0.81) vs. non-HIV 2.72 (0.42), p = 0.012), with signs of systolic and diastolic dysfunction (isovolumic relaxation time: HIV 52.2 ms (8.85) vs. non-HIV 42.5 ms (7.30); p<0.001). Cord blood mitochondrial content was significantly increased in HIV-exposed fetuses (CS activity: HIV 82.9 nmol/min.mg of protein (SD 40.5) vs. non-HIV 56.7 nmol/min.mg of protein (28.4); p = 0.007), with no differences in mtDNA content and COX activity. Both myocardial and mitochondrial mass parameters were significantly associated with zidovudine exposure.

Conclusions: HEU fetuses showed signs of increased myocardial and mitochondrial mass associated with maternal zidovudine treatment, suggesting a fetal adaptive response to cART toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active*
  • Case-Control Studies
  • Echocardiography
  • Female
  • Fetal Blood
  • Fetus / drug effects
  • Fetus / pathology*
  • Fetus / virology
  • Gestational Age
  • HIV / drug effects*
  • HIV / isolation & purification
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • Heart / drug effects
  • Heart / physiopathology*
  • Heart / virology
  • Humans
  • Maternal-Fetal Exchange
  • Mitochondria / drug effects
  • Mitochondria / pathology*
  • Mitochondria / virology
  • Pregnancy
  • Pregnancy Complications, Infectious / epidemiology*
  • Pregnancy Complications, Infectious / virology
  • Prenatal Exposure Delayed Effects / epidemiology*
  • Prenatal Exposure Delayed Effects / virology
  • Prospective Studies

Grants and funding

This study was supported by grants from Instituto de Salud Carlos III (grants PI13/01738, PI14/00226, PI15/00130, PI15/00263 and INT16/00168) integrados en el Plan Nacional de I+D+I y cofinanciados por el ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) “Otra manera de hacer Europa”, the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya (2014 SGR grant n° 928, 2016FI_B01184) Spain and European Social Funds, “la Caixa” Foundation (Spain), the Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK) and Erasmus + Programme of the European Union (Framework Agreement number: 2013-0040) [This publication reflects the views only of the author, and the Commission cannot be held responsible for any use which may be made of the information contained therein]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.