Patho-immune Mechanisms of Hypertension in HIV: a Systematic and Thematic Review

Abstract

Purpose of Review To systematically review recent findings on the role of immune cell activation in the pathogenesis of hypertension in people living with HIV (PLWH) and compare studies from Sub-Saharan Africa with what is reported in the USA and European literature according to guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Recent Findings PLWH have an increased risk for development of hypertension and cardiovascular disease. Chronic immune activation contributes to hypertension but the inflammatory milieu that predisposes PLWH to hypertension is poorly understood. We identified 45 relevant studies from 13 unique African countries. The prevalence of hypertension in PLWH on antiretroviral therapy (ART) and the ART-naive PLWH ranged from 6 to 50% and 2 to 41%, respectively. Interleukin (IL)-17A, interferon (IFN)-γ, and higher CD4 + T cell counts were associated with hypertension in ART-treated participants. Summary Targeting adaptive immune activation could provide improved care for hypertensive PLWH. Further research is needed to characterize the inflammatory milieu contributing to hypertension in PLWH especially in African populations where the global burden of HIV is the highest.

Hypertension and Metabolic Syndrome in Persons with HIV

“…In many studies, hypertension is more prevalent in ART-treated than in ART-naïve PWH and in ART-naïve than in HIV-negative subjects [ 34 •]. In the HIV-HY study, prevalence of established plus pre-hypertension was 41.6%, with only two-thirds aware and one-third controlled despite the use of mono or combined therapies, with three-quarter of patients receiving antagonists of the RAS [ 35 ].…”

“…Aging, the metabolic abnormalities, endothelial dysfunction, and inflammation of HIV infection and ART treatment for longer than 2 years are the drivers of hypertension in PWH [ 2 ••]. Some have shown that central obesity and overweight increased the risk of hypertension and MetS in PWH as they do in the general population [ 9 •], whereas others reported that nadir CD4 T cell counts were also associated with hypertension in European [ 35 ] and African [ 34 •] PWH, a finding specific to HIV populations. In addition to HIV-related inflammation and detrimental effects of ART on adipocyte health and lipid metabolism, specific components of the virus such as the negative factor (Nef) protein, transcription protein (Tat), and glycoprotein 120 may contribute to the link between MetS and hypertension in PWH, perhaps superimposed on individual genetic predisposition [ 36 – 38 ].…”

“…There is growing evidence that hypertension is an immune-related condition with various non-immune interplaying factors. We have shown that in PWH, hypertension is associated with increased levels of inflammatory (IL-6, IL-17, tumor necrosis factor-alpha receptor 1, IL-5, intercellular adhesion molecule 1, macrophage inflammatory protein-1 alpha, elevated eosinophils) and with immune-activation markers independently from the other components of MetS [ 34 •, 39 ••]. Inflammatory markers such as hsCRP and IL-6 are increased in PWH with MetS compared with those without MetS [ 2 ••], suggesting that inflammation of MetS plays a role in the pathogenesis of hypertension in PWH.…”

High prevalence of non-communicable diseases among key populations enrolled at a large HIV prevention & treatment program in Kenya

“…There are mixed associations with ART use on the prevalence of NCDs with some studies suggesting no associations with hypertension [23,31] while others finding an increased odds for hypertension, dyslipidemia and other cardiovascular conditions [29,30,32]. Although chronic immune activation contributes to increased hypertension among PLHIV, the inflammatory milieu is poorly understood [33]. ART associated endothelial dysfunction [34], increasing age and longevity on ART treatment have also been associated with increased prevalence of NCDs among PLHIV [23,30,32].…”

HIV Research Training Partnership of the University of Zambia and Vanderbilt University: Features and Early Outcomes

“…The UNZA research community is envisioned as comprising both UNZA PhD graduates and their mentors who have participated in a shared UVP-supported research training process, have built collaborations with Vanderbilt investigators, [1516171819202122] and are pursuing research careers focused on nutrition/metabolism-related long-term non-communicable complications and comorbidities of HIV. It will take time for these communities to mature, but there is concrete early evidence of it, including UVP students who are farther along in their careers and UVP alumni co-mentoring trainees who are earlier in their studies, and publications and grant applications being submitted by UNZA/Vanderbilt mentor-mentee teams that have convened through UVP support.…”