Hypertension and Metabolic Syndrome in Persons with HIV

Abstract

Purpose of review: With the advent of highly active antiretroviral therapy (ART), the life span of persons with HIV (PWH) has been nearly normalized. With aging, prevalence of the metabolic syndrome (MetS), including hypertension, has increased in the HIV population and exceeds that in the general population in some studies. This is due to a combination of traditional risk factors in addition to the effects attributable to the virus and ART. We review recent findings on the mechanisms contributing to MetS and hypertension in PWH, particularly those specific to the viral infection and to ART.

Recent findings: Activation of the renin-angiotensin-aldosterone system (RAAS) and chronic immune activation contribute to the development of MetS and hypertension in PWH. HIV proteins and some ART agents alter adipocyte health contributing to dyslipidemias, weight gain, and insulin resistance. HIV infection also contributes to hypertension by direct effects on the RAAS that intertwine with inflammation by the RAAS also contributing to T cell activation. Recent data suggest that in addition to current ART, therapeutic targeting of the MetS and hypertension in PWH, by interfering with the RAAS, treating insulin resistance directly or by use of immunomodulators that dampen inflammation, may be critical for preventing or treating these risk factors and to improve overall cardiovascular complications in the HIV-infected aging population.

Keywords: Antiretroviral therapy; HIV; Hypertension; Immune modulators; Metabolic syndrome.

Fig. 1

HIV-related chronic immune activation, ART effects, and lifestyle contribute to hypertension and metabolic syndrome. Infected dendritic cells (DCs) through toll-like receptor (TLR) stimulation activate CD8 cytotoxic cells that have direct vascular effects on the endothelial cells. Immune-activation is accompanied by expression of CD38+ and human leukocyte antigen D-related (HLA-DR) expression on T cells, markers associated with disease progression. Activated endothelial cells increase the expression of platelet derived growth factors, intercellular adhesion molecule-1 and vascular adhesion molecule-1 which increases leukocyte adhesion to the vessel producing a fertile environment for atherosclerotic events. Endothelin-1 produced by endothelial cells leads to vasoconstriction. Binding of HIV to CD4 cells through the glycoprotein (gp) 120/41 downregulates T cell receptor (TCR) leading to cell death. CD4 T-regulatory (Treg) cells responsible for induction of anti-inflammatory IL-10 is rendered dysfunctional in HIV leading to overactivation of immune system resulting in persistent chronic immune activation. Microbial translocation into blood circulation due to depleted CD4 cells in the gut further exacerbate the inflammation. All these vascular events contribute to hypertension through direct damage from cells and inflammatory cytokines such as IL-17 and IL-6. T cells infiltrate the kidneys producing inflammatory cytokines resulting in increased sodium retention, vascular remodeling, and endothelial dysfunction and hypertension. Effects of ART causes HIV-associated lipodystrophy syndrome (HALS). Increased adipose tissue macrophage infiltrate the adipocytes resulting in secretion of adipokines that induce increased insulin resistance. In addition, lifestyle factors such as aging and diet synergize with ART effects and chronic immune activation and contribute to MetS components especially hypertension and increase risk of MetS