Telmisartan to reduce cardiovascular risk in older HIV-infected adults: a pilot study

Abstract

Background HIV-infected persons are at increased cardiovascular disease (CVD) risk, but traditional CVD therapies are understudied in this population. Telmisartan is an angiotensin receptor blocker and PPAR-γ agonist that improves endothelial function and cardiovascular mortality in HIV-uninfected populations. We assessed the effects of telmisartan on endothelial function in older HIV-infected persons at risk for CVD in a small pilot study. Methods HIV-infected individuals ≥50 years old on suppressive antiretroviral therapy (ART) with ≥1 traditional CVD risk factor received open label telmisartan 80 mg daily for six weeks. Brachial artery flow-mediated dilation (FMD) measured endothelial function. The primary endpoint was six-week change in maximum relative FMD. Results Seventeen participants enrolled; 16 completed all evaluations (88% men, 65% non-White, median age 60 years, CD4+ T lymphocyte count 625 cells/mm3). ART included 71% PI, 29% NNRTI, 29% integrase inhibitor, 65% tenofovir and 29% abacavir. CVD risk factor prevalence included 76% hyperlipidemia, 65% hypertension, 18% smoking and 12% diabetes mellitus. After six weeks, statistically significant blood pressure changes were observed (systolic −16.0 mmHg, diastolic −6.0 mmHg) without significant changes in FMD. In subset analyses, FMD increased more among abacavir-treated, PI-treated and non-smoking participants. Conclusions No significant FMD changes were observed after six weeks of telmisartan therapy; however, abacavir- and PI-treated participants and non-smokers showed greater FMD increases. Additional studies are needed to explore the effects of telmisartan on endothelial function among HIV-infected individuals with traditional CVD and/or ART-specific risk factors.

Impact of switching to raltegravir and/or adding losartan in lymphoid tissue fibrosis and inflammation in people living with HIV. A randomized clinical trial

“…Different results have been published with heterogeneous conclusions depending on the ARB used or the marker studied [9]. The studies with ARBs in PLWH published so far investigated the effect of antagonizing angiotensin in people living with HIV‐associated nephropathy in a mice model [15] and, in humans, two pilot studies assessed cardiovascular risk and visceral fat after intervention with telmisartan [16,17]. We performed a 48‐week study with the maximum dose of losartan used for hypertension (100 mg) added to the strategy of changing the third antiretroviral agent to raltegravir.…”

The Youngbloods. Get Together. Hypercoagulation, Complement, and NET Formation in HIV/SIV Pathogenesis

“…(iii) Angiotensin receptor blockers have also been evaluated in PWH, to assess their potential benefits in reducing endothelial injury. After a 3-month prospective study, telmisartan administration led to an increase in endothelial progenitor cells, but had no effect on immune activation (162)(163)(164). (iv) Ixolaris, a TF inhibitor that blocks the extrinsic coagulation pathway at its origin, is a promising candidate for the treatment of hypercoagulation in PWH.…”

Mechanisms and primary prevention of atherosclerotic cardiovascular disease among people living with HIV

“…PLWH have high plasma renin activity, possibly related to the structural similarity between renin and HIV-protease, production of renin by CD4 þ T cells stimulated by HIV-1, and reninstimulated viral reproduction [50,[56][57][58]. Several small trials of telmisartan, an angiotensin receptor blocker and peroxisome proliferator-activated receptor-g agonist, showed impressive blood pressure reductions [59][60][61]. A study of losartan demonstrated decreased blood pressure but no improvement in inflammation or T-cell recovery [62 & ].…”