Assessment of the impact of HIV infection and anti-retroviral treatment on the cardiometabolic health of pregnant mothers and their offspring (ARTMOMSBABES)

Abstract

Background The risk of cardiovascular diseases (CVDs) is becoming more prevalent in pregnant women though not much data is available for pregnant women with human immunodeficiency virus (HIV). Foetoplacental vascular endothelial dysfunction is thought to be at the origin of chronic diseases such as diabetes and obesity later on in life. Because HIV and anti-retroviral treatment (ARTs) are associated with endothelial dysfunction, children exposed in utero to these conditions may be at greater risk of developing CVDs. Despite the high prevalence of HIV in pregnant South African women, little is known about the effects of ART on the cardiovascular health of the mother and offspring. Hence, the proposed study intends to investigate how HIV/ARTs may affect the cardiovascular health of the mother and offspring at different time points during the pregnancy and up to 2 years after birth. Methods A longitudinal case–control study in HIV positive pregnant women on ART and HIV negative pregnant women will be conducted. All pregnant women will be assessed for cardio-metabolic risk factors and markers (lipids, anthropometric and glycaemic indies, oxidative stress), hemodynamic status (blood pressure parameters) and vascular function (arterial compliance, retinal microvasculature, uterine artery mean pulsatility index). Child health will be monitored in utero and postnatally via routine foetal health screening, placental integrity, anthropometry, blood pressure parameters, markers of oxidative stress and endothelial function in cord blood and cardiovascular epigenetic markers in urine. Discussion There is a paucity of studies in South Africa and sub-Sahara Africa as a whole that utilised a longitudinal study model to assess the effects of ARTs on vascular endothelial changes in pregnant women living with HIV and the cardiometabolic health of their offspring. This study will therefore help to monitor changes in cardiometabolic risk during pregnancy and in children exposed in utero to HIV-infection and ART use. Findings from this study will provide useful information for developing guidelines on the use of ARTs in pregnancy and management of cardiometabolic health of the offspring of HIV positive mothers.

Maternal overweight and obesity and its associated factors and outcomes in human immunodeficiency virus (HIV)‐infected and HIV‐uninfected black South African pregnant women

“…46 In terms of the HIV infection and treatment thereof, it is of particular interest in South African pregnant women, because it has been linked to vascular endothelial dysfunction. 47 Our study identified that overweight and obese HIVinfected pregnant women had increased odds for developing HPT disorders. Another study has supported this, where HIV-infected pregnant women with a BMI ≥25 kg/m 2 had a significantly increased odds of HPT disorders like PET (OR = 3.0; 95% CI: 1.5-6.0).…”

“…For example, in a retrospective cohort study it was identified that maternal overweight or obesity in pregnancy was associated with a significantly increased odds of developing hypertensive disorders in comparison to pregnant women with a BMI <25 kg/m 2 46 . In terms of the HIV infection and treatment thereof, it is of particular interest in South African pregnant women, because it has been linked to vascular endothelial dysfunction 47 . Our study identified that overweight and obese HIV‐infected pregnant women had increased odds for developing HPT disorders.…”

The molecular mechanisms in prenatal drug exposure-induced fetal programmed adult cardiovascular disease

“…Fetoplacental vascular endothelial dysfunction was thought to be at the origin of chronic diseases such as diabetes and obesity later in life. As HIV and antiretroviral therapies were found to be associated with endothelial dysfunction and change in the intrauterine environment, children exposed in utero to these conditions were considered to be at greater potential risk of programmed cardiovascular diseases by epigenetic regulation ( Nkeh-Chungag et al, 2021 ). An in vivo experiment confirmed that the administration of combination antiretroviral therapy was associated with poor placental insertion and development of IUGR.…”

A Systematic Review on Cardiometabolic Risks and Perinatal Outcomes among Pregnant Women Living with HIV in the Era of Antiretroviral Therapy

“…Moreover, pregnant women who start ART prior to the onset of their pregnancy have different baseline biochemical characteristics than women who start ART during pregnancy [ 12 ]. Although evidence shows a high prevalence of cardiometabolic risk (CMR) in pWLWH, little is known about the effect of ART on their cardiometabolic health [ 14 , 15 , 16 , 17 ]. Some possible mechanisms involved may include complex interactions of HIV, ART, and chronic inflammation [ 18 , 19 ].…”