Maternal endothelial dysfunction in HIV-associated preeclampsia comorbid with COVID-19: a review.

ABSTRACT

This review assesses markers of endothelial dysfunction (ED) associated with the maternal syndrome of preeclampsia (PE). We evaluate the role of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected preeclamptic women. Furthermore, we briefly discuss the potential of lopinavir/ritonavir (LPV/r), dolutegravir (DTG) and remdesivir (RDV) in drug repurposing and their safety in pregnancy complicated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In HIV infection, the trans-activator of transcription protein, which has homology with vascular endothelial growth factor, impairs angiogenesis, leading to endothelial injury and possible PE development despite neutralization of their opposing immune states. Markers of ED show strong evidence supporting the adverse role of ART in PE development and mortality compared to treatment-naïve pregnancies. Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 infection, exploits angiotensin-converting enzyme 2 (ACE 2) to induce ED and hypertension, thereby mimicking angiotensin II-mediated PE in severe cases of infection. Upregulated ACE 2 in pregnancy is a possible risk factor for SARS-CoV-2 infection and subsequent PE development. The potential effectiveness of LPV/r against COVID-19 is inconclusive; however, defective decidualization, along with elevated markers of ED, was observed. Therefore, the safety of these drugs in HIV-positive pregnancies complicated by COVID-19 requires attention. Despite the observed endothelial protective properties of DTG, there is a lack of evidence of its effects on pregnancy and COVID-19 therapeutics. Understanding RDV-ART interactions and the inclusion of pregnant women in antiviral drug repurposing trials is essential. This review provides a platform for further research on PE in the HIV-COVID-19 syndemic.