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Telmisartan increases vascular reparative capacity in older HIV-infected adults: a pilot study.

ABSTRACT: Endothelial progenitor cells (EPCs) are bone marrow-derived cells that contribute to vascular repair. EPCs may be reduced in HIV-infected (HIV+) persons, contributing to cardiovascular disease (CVD). Telmisartan is an angiotensin receptor blocker that increases EPCs in HIV-uninfected adults.To assess telmisartan's effects on EPC number and immunophenotype in older HIV + adults at risk for CVD.HIV + persons ?50 years old with HIV-1 RNA < 50 copies/mL on suppressive antiretroviral therapy and ?1 CVD risk factor participated in a prospective, open-label, pilot study of oral telmisartan 80 mg daily for 12 weeks. Using CD34 and CD133 as markers of early maturity and KDR as a marker of endothelial lineage commitment, EPCs were quantified via flow cytometry and defined as viable CD3-/CD33-/CD19-/glycophorin- cells of four immunophenotypes: CD133+/KDR+, CD34+/KDR+, CD34+/CD133+, or CD34+/KDR+/CD133+. The primary endpoint was a 12-week change in EPC subsets (NCT01578772).Seventeen participants (88% men, median age 60 years and peripheral CD4+ T lymphocyte count 625 cells/mm3) enrolled and completed the study. After 6 and 12 weeks of telmisartan, frequencies of all EPC immunophenotypes were higher than baseline (all p < 0.10 except week 12 CD133+/KDR+ EPC, p = 0.13). Participants with lower baseline EPC levels had the largest gains. Additionally, the percentage of CD34+ cells with endothelial commitment (KDR+) increased.Our data suggest that telmisartan use is associated with an increase in circulating EPCs in older HIV + individuals with CVD risk factors. Further controlled studies are needed to assess whether EPC increases translate to a reduction in CVD risk in this population.

SUBMITTER: Lake JE

PROVIDER: S-EPMC5470589 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Telmisartan increases vascular reparative capacity in older HIV-infected adults: a pilot study.

Lake Jordan E JE Seang Sophie S Kelesidis Theodoros T Currier Judith S JS Yang Otto O OO

HIV clinical trials 20160923 6

<h4>Background</h4>Endothelial progenitor cells (EPCs) are bone marrow-derived cells that contribute to vascular repair. EPCs may be reduced in HIV-infected (HIV+) persons, contributing to cardiovascular disease (CVD). Telmisartan is an angiotensin receptor blocker that increases EPCs in HIV-uninfected adults.<h4>Objective</h4>To assess telmisartan's effects on EPC number and immunophenotype in older HIV + adults at risk for CVD.<h4>Methods</h4>HIV + persons ≥50 years old with HIV-1 RNA < 50 cop ...[more]

PMID: 27658740

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Project description:Background: HIV-infected adults have increased risk for age-related diseases and low cardiorespiratory fitness that can be prevented and improved with exercise. Yet, exercise strategies have not been well studied in older adults with HIV and may require substantial adaptation to this special population.Objective: To determine the safety and efficacy of aerobic exercise in older HIV-infected men in a randomized trial comparing different levels of exercise intensity.Methods: We conducted a pilot exercise trial in 22 HIV-infected men ?50 years of age receiving antiretroviral therapy who were randomized 1:1 to moderate-intensity aerobic exercise (Mod-AEX) or high-intensity aerobic exercise (High-AEX) that was performed three times weekly for 16 weeks in a supervised setting. Primary outcome was cardiorespiratory fitness (VO2peak) measured by treadmill testing. Secondary outcomes were exercise endurance, six-minute walk distance (6-MWD), body composition measured by Dual-energy X-ray absorptiometry (DXA), and fasting plasma levels of lipids and glucose.Results: VO2peak increased in the High-AEX group (3.6 ±1.2 mL/kg/min, p = 0.02) but not in the Mod-AEX group (0.4 ±1.4 mL/kg/min, p = 0.7) with a significant between group difference (p<0.01). Exercise endurance increased in both the High-AEX group (27 ±11%, p = 0.02) and the Mod-AEX group (11 ±4%, p = 0.04). The 6-MWD increased in both the High-AEX (62 ±18m, p = 0.01) and the Mod-AEX group (54 ±14m, p = 0.01). Changes in VO2peak and 6-MWD were clinically relevant. There were no serious exercise-related adverse events. Dropouts were similar between group (27% overall) and were related to joint pain.Conclusions: This pilot exercise trial demonstrates that moderate to high-intensity aerobic exercise in older HIV-infected men increases endurance and ambulatory function. However, increased cardiorespiratory fitness was observed only with high-intensity aerobic exercise despite substantial baseline impairment. Future research is needed to determine exercise strategies in older HIV-infected adults that address advanced aging and comorbidity yet are durable and feasible.

Project description:BackgroundCardiovascular disease (CVD) and premature aging have been hypothesized as new risk factors for HIV associated neurocognitive disorders (HAND) in adults with virally-suppressed HIV infection. Moreover, their significance and relation to more classical HAND biomarkers remain unclear.Methods92 HIV- infected (HIV+) adults stable on combined antiretroviral therapy (cART) and 30 age-comparable HIV-negative (HIV-) subjects underwent (1)H Magnetic Resonance Spectroscopy (MRS) of the frontal white matter (targeting HIV, normal aging or CVD-related neurochemical injury), caudate nucleus (targeting HIV neurochemical injury), and posterior cingulate cortex (targeting normal/pathological aging, CVD-related neurochemical changes). All also underwent standard neuropsychological (NP) testing. CVD risk scores were calculated. HIV disease biomarkers were collected and cerebrospinal fluid (CSF) neuroinflammation biomarkers were obtained in 38 HIV+ individuals.ResultsRelative to HIV- individuals, HIV+ individuals presented mild MRS alterations: in the frontal white matter: lower N-Acetyl-Aspartate (NAA) (p<.04) and higher myo-inositol (mIo) (p<.04); in the caudate: lower NAA (p?=?.01); and in the posterior cingulate cortex: higher mIo (p<.008- also significant when Holm-Sidak corrected) and higher Choline/NAA (p<.04). Regression models showed that an HIV*age interaction was associated with lower frontal white matter NAA. CVD risk factors were associated with lower posterior cingulate cortex and caudate NAA in both groups. Past acute CVD events in the HIV+ group were associated with increased mIo in the posterior cingulate cortex. HIV duration was associated with lower caudate NAA; greater CNS cART penetration was associated with lower mIo in the posterior cingulate cortex and the degree of immune recovery on cART was associated with higher NAA in the frontal white matter. CSF neopterin was associated with higher mIo in the posterior cingulate cortex and frontal white matter.ConclusionsIn chronically HIV+ adults with long-term viral suppression, current CVD risk, past CVD and age are independent factors for neuronal injury and inflammation. This suggests a tripartite model of HIV, CVD and age likely driven by chronic inflammation.

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Telmisartan increases vascular reparative capacity in older HIV-infected adults: a pilot study.

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Telmisartan increases vascular reparative capacity in older HIV-infected adults: a pilot study.

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