HIV Associated Preeclampsia: A Multifactorial Appraisal

Abstract

Introduction: This review explores angiogenesis, vascular dysfunction, the complement system, RAAS, apoptosis and NETosis as potential pathways that are dysregulated during preeclampsia, HIV infection and ART usage. Results: HIV-1 accessory and matrix proteins are protagonists for the elevation of oxidative stress, apoptosis, angiogenesis, and elevation of adhesion markers. Despite the immunodeficiency during HIV-1 infection, HIV-1 exploits our cellular defence arsenal by escaping cell-mediated lysis, yet HIV-1 infectivity is enhanced via C5a release of TNF-α and IL-6. This review demonstrates that PE is an oxidatively stressed microenvironment associated with increased apoptosis and NETosis, but with a decline in angiogenesis. Immune reconstitution in the duality of HIV-1 and PE by protease inhibitors, HAART and nucleoside reverse transcriptase, affect similar cellular pathways that eventuate in loss of endothelial cell integrity and, hence, its dysfunction. Conclusions: HIV-1 infection, preeclampsia and ARTs differentially affect endothelial cell function. In the synergy of both conditions, endothelial dysfunction predominates. This knowledge will help us to understand the effect of HIV infection and ART on immune reconstitution in preeclampsia.

Keywords: HIV; Netosis; RAAS; angiogenesis; antiretroviral therapy; complement system; preeclampsia.

Figure 1

The homology between HIV-1 and PE response to endothelial dysfunction. HIV-1 accessory proteins gp120, tat and nef, as well as matrix proteins, are protagonists of the cellular machinery that culminate in endothelial cell dysfunction. Adapted from [30].

Figure 2

HIV-1 accessory protein Tat is released from infected cells, decreases bioavailability of VEGF and increases cell adhesion expression, thereby promoting endothelial cell dysfunction. Adapted from [67,68].