Research Article: Impact of HIV-1 infection on the IGF-1 axis and angiogenic factors in pregnant Cameroonian women receiving antiretroviral therapy

Date Published: May 1, 2019

Publisher: Public Library of Science

Author(s): Livo F. Esemu, Emile K. Yuosembom, Rui Fang, Shayne Rasay, Barriere A. Y. Fodjo, John T. Nguasong, Winifrida Kidima, Gabriel L. Ekali, John J. Chen, Lishomwa Ndhlovu, Jude D. Bigoga, Diane W. Taylor, Rose G. F. Leke, Anna Babakhanyan, Daniel Gemechu Datiko.

http://doi.org/10.1371/journal.pone.0215825

Abstract

Although mother-to-child transmission of HIV has dramatically declined, the number of in utero HIV-exposed, uninfected infants is on the increase. HIV-exposed infants are at an increased risk of mortality, morbidity and slower early growth than their non-HIV exposed counterparts. Maternal HIV increases the risk of having preterm deliveries, intrauterine growth restriction and low birth weight babies. However, the mechanism underlying dysregulation of fetal growth in HIV-infected pregnant women is unknown. We sought to determine whether maternal HIV is associated with dysregulation of the insulin-like growth factor (IGF) axis, some angiogenic factors or other related biomarkers that regulate fetal growth. A total of 102 normotensive pregnant women were enrolled in a small cross-sectional study. Amongst these were thirty-one HIV-1 positive women receiving combination antiretroviral therapy (cART) (Mean age: 30.0 ± 5.1 years; % on ART: 83.9%; median plasma viral load: 683 copies/ml; median CD4 count: 350 cells/ul) and 71 HIV uninfected women (mean age: 27.3 ± 5.8) recruited at delivery. A panel of biomarkers including IGF1 and IGF binding proteins (IGFBP1, IGFBP3), angiopoietins (ANG) 1 and 2, matrix metalloproteinases (MMP) 2 and 9, and galectin 13, was measured in plasma collected from the placental intervillous space. The levels of IGF1, IGFBP1, ANG1, ANG2, MMP2, MMP9 and Gal-13 were not affected by maternal HIV, even when adjusted for maternal factors in linear regression models (all p>0.05). It was observed that HIV-infection in pregnancy did not significantly affect key markers of the IGF axis and angiogenic factors. If anything, it did not affect women. These findings highlight the importance of the use of ART during pregnancy, which maintains factors necessary for fetal development closer to those of healthy women. However, decrease in IGF1 levels might be exacerbated in women con-infected with HIV and malaria.

Partial Text

In sub-Saharan Africa, women disproportionately bear the burden of the HIV epidemic [1,2]. Each year, 1.4 million HIV-infected women become pregnant [1], with up to 5.3% of those pregnant being HIV positive in many African countries [3]. In Cameroon, the national HIV prevalence in 2011 was 5.6% in women and 2.9% in men, but the prevalence of HIV among pregnant women was 7.8% [3,4]. Maternal HIV-1 infection increases the risk of pre-term birth (<37 weeks of gestation), small-for-gestational age babies, and fetal intrauterine growth restriction [5–9], resulting in low birth weight (LBW) infants (<2500g) [10–12]. Low birth weight occurs in over 20 million children and 95% of this condition is observed in developing countries [13,14]. Approximately 10% of children born to HIV positive Cameroonian women under prolonged HAART were born with LBW[15]. LBW is a significant cause of infant morbidity and increases the risk of mortality during the first year of life by 40-fold [16]. The goal of our study was to determine whether maternal HIV is associated with the dysregulation of insulin-like growth factor (IGF) axis, angiogenic factors—or other related biomarkers that regulate fetal growth. In this pilot study, a panel of biomarkers implicated in placental homeostasis and fetal growth were assessed in intervillous space plasma of HIV-1 positive normotensive women on antiretroviral therapy and their HIV-1 negative counterparts. This panel of biomarkers included those involved in angiogenesis, IGF axis, as well as profile of MMPs and Gal-13. Angiogenic factors were not affected by maternal HIV-1 in our cohort of pregnant women receiving antiretroviral therapy. Angiopoetins 1 and 2 levels were not significantly different between HIV-1 positive and healthy women, even after adjusting for maternal factors.   Source: http://doi.org/10.1371/journal.pone.0215825

 

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