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

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.

SUBMITTER: Esemu LF

PROVIDER: S-EPMC6493724 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Esemu Livo F LF Yuosembom Emile K EK Fang Rui R Rasay Shayne S Fodjo Barriere A Y BAY Nguasong John T JT Kidima Winifrida W Ekali Gabriel L GL Chen John J JJ Ndhlovu Lishomwa L Bigoga Jude D JD Taylor Diane W DW Leke Rose G F RGF Babakhanyan Anna A

PloS one 20190501 5

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 i ...[more]

PMID: 31042729

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Project description:OBJECTIVE:We identified clinical, dietary, and socioeconomic factors associated with insufficient gestational weight gain among Mexican pregnant women with human immunodeficiency virus (HIV) infection. METHODS:This was a cross-sectional study involving 112 pregnant women with HIV infection receiving antiretroviral therapy (ART). Data including viral load, complete blood analysis, and CD4 counts were extracted from medical records. An inquiry form was used to collect data on socioeconomic status and frequency of food intake. Pre-gestational weight was calculated based on pregnancy weight to obtain the body mass index (BMI) and weight gain for gestational age according the US Institute of Medicine. Of the study population, 68.7% were in consensual union, 31.3% were single, and 33.9% belonged to the two lowest socioeconomic strata. The median age and CD4 count were 27 (interquartile range [IQR]: 23-32) years and 418 (IQR: 267-591), respectively. The adequacy of energy was 91.8% (IQR: 74.1-117.7). The median energy intake from protein was 13.5% (IQR: 12.2-14.9) and from lipids, 35.5% (IQR: 31.1-40.3). Pregnant women with gastrointestinal symptoms and CD4 count <350 were seven times more likely to have folate deficiency (odds ratio [OR] 7.8, 95% confidence interval [CI] 1.6-38.1; p = 0.009) and six times more likely to have poor zinc intake (OR 6.7, 95% CI 1.3-36.8; p = 0.014). In all, 42.9% of the pregnant women consumed iron and folic acid supplements and 54.4% consumed multivitamin supplements. Moreover, 45.5% had a normal pre-gestational BMI, 41.1% were classified overweight, and 13.4% had obesity, whereas 62.5% showed insufficient gestational weight gain, and 18.8% experienced weight loss. The variables associated with insufficient weight gain were consensual union (OR 5.3, 95% CI 1.9-15.0; p = 0.002) and belonging to the lowest socioeconomic stratum (E) (OR 3.1, 95% CI 1.0-9.2; p = 0.046). CONCLUSION:Dietary strategies to improve gestational weight gain for Mexican women with HIV infection receiving ART must consider clinical and socioeconomic factors.

Project description:BACKGROUND: Long term use of antiretroviral therapy (ART) in persons living with human immunodeficiency virus (PLWHIV) is associated with disturbances in blood lipids which should be monitored. More data on such disturbances are needed in Cameroon to persuade the country program to institute their routine monitoring. We then sought to determine the prevalence and timing of dyslipidaemia in PLWHIV and receiving ART in a predominantly rural Cameroonian setting. METHODS: A cross-sectional study conducted between August and October 2012 in HIV-infected persons aged 15 years or more and receiving first-line ART for at least six months at The Nkongsamba Regional Hospital in Cameroon. Lipid assays were carried out by enzymatic-linked colorimetric methods. A multiple logistic regression model was used to assess for factors related to dyslipidaemia. RESULTS: Included were 114 participants of whom 83 (72.8%) were females. Their median age was 43 years (IQR: 36-51) and their median CD4 count was 436 cells/?l (IQR: 275-585) after a median duration on ART of 36 months (IQR: 12-60). The prevalence of dyslipidaemia was 70.2%. Hypercholesterolaemia was observed in 34 (29.8%) patients. One-third of them had a high LDL-cholesterol level (LDL-c?130 mg/dl). Hypertriglyceridaemia (TG?150 mg/dl) was present in 59 (51.8%) cases. The proportion of patients with a low HDL-cholesterol (HDL-c<40 mg/dl) was 18.4% while those with a ratio of TC/HDL-c?5 were about 16.7%. A duration of 2-4 years on ART (adjusted Odd Ratio, aOR=5.22, 95% CI: 1.43-19.06, p=0.01), current smokers (aOR=15.94, 95% CI: 1.13-225.61, p=0.04) and a concurrent metabolic disease (aOR=12.54, 95% CI: 1.02-153.86, p=0.48) were independently associated with pro-atherogenic LDL-c values. Alcohol users had a more friendly LDL-c profile (aOR=0.24, 95% CI: 0.07-0.74, p=0.01). CONCLUSION: The study has demonstrated a high prevalence of dyslipidaemia in HIV-patients receiving first-line ART in a predominantly rural setting of Cameroon. There is a need for the country HIV program to institute laboratory monitoring of blood lipids in patients over two years on first line ART with a focus on smokers.

Project description:BackgroundMaternal HIV increases the risk of adverse birth outcomes including preterm birth, fetal growth restriction, and stillbirth, but the biological mechanism(s) underlying this increased risk are not well understood. We hypothesized that maternal HIV may lead to adverse birth outcomes through an imbalance in angiogenic factors involved in the vascular endothelial growth factor (VEGF) signaling pathway.MethodsIn a case-control study nested within an ongoing cohort in Zambia, our primary outcomes were serum concentrations of VEGF-A, soluble endoglin (sEng), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFLT-1). These were measured in 57 women with HIV (cases) and 57 women without HIV (controls) before 16 gestational weeks. We used the Wilcoxon rank-sum and linear regression controlling for maternal body mass index (BMI) and parity to assess the difference in biomarker concentrations between cases and controls. We also used logistic regression to test for associations between biomarker concentration and adverse pregnancy outcomes (preeclampsia, preterm birth, small for gestational age, stillbirth, and a composite of preterm birth or stillbirth).ResultsCompared to controls, women with HIV had significantly lower median concentrations of PlGF (7.6 vs 10.2 pg/mL, p = 0.02) and sFLT-1 (1647.9 vs 2055.6 pg/mL, p = 0.04), but these findings were not confirmed in adjusted analysis. PlGF concentration was lower among women who delivered preterm compared to those who delivered at term (6.7 vs 9.6 pg/mL, p = 0.03) and among those who experienced the composite adverse birth outcome (6.2 vs 9.8 pg/mL, p = 0.02). Median sFLT-1 concentration was lower among participants with the composite outcome (1621.0 vs 1945.9 pg/mL, p = 0.04), but the association was not significant in adjusted analysis. sEng was not associated with either adverse birth outcomes or HIV. VEGF-A was undetectable by Luminex in all specimens.ConclusionsWe present preliminary findings that HIV is associated with a shift in the VEGF signaling pathway in early pregnancy, although adjusted analyses were inconclusive. We confirm an association between angiogenic biomarkers and adverse birth outcomes in our population. Larger studies are needed to further elucidate the role of HIV on placental angiogenesis and adverse birth outcomes.

Dataset Information

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

Publications

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

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