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

Date Published: March 4, 2019

Publisher: Public Library of Science

Author(s): Laura García-Otero, Marta López, Mariona Guitart-Mampel, Constanza Morén, Anna Goncé, Carol Esteve, Laura Salazar, Olga Gómez, Josep María Martínez, Berta Torres, Sergi César, Glòria Garrabou, Fàtima Crispi, Eduard Gratacós, Giuseppe Vittorio De Socio.

http://doi.org/10.1371/journal.pone.0213279

Abstract

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.

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).

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

Partial Text

Perinatal transmission of Human Immunodeficiency Virus (HIV) is mainly prevented by combined antiretroviral treatment (cART) during pregnancy [1]. In 2016, about 76% [60–88%] of pregnant women living with HIV worldwide had access to cART [1–4]. As a result, the number of HIV-exposed uninfected (HEU) children has been on the rise, with health conditions presented, even if mild, having a potentially noteworthy public health impact [5]. Indeed, it is well known that an adverse prenatal environment during the critical period of in utero fetal development might have long lasting consequences on health [6].

In the present study, we found signs of increased fetal myocardial mass and mitochondrial content most likely enabling a preserved cardiac ejection fraction and mitochondrial function in HEU fetuses exposed to maternal cART. Both cardiovascular and mitochondrial mass-related parameters were significantly associated with zidovudine exposure.

 

Source:

http://doi.org/10.1371/journal.pone.0213279

 

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