Losartan to reduce inflammation and fibrosis endpoints in HIV disease

Jason V. Baker, Julian Wolfson, Gary Collins, Caryn Morse, Frank Rhame, Angelike P. Liappis, Stacey Rizza, Zelalem Temesgen, Harry Mystakelis, Steven Deeks, James Neaton, Timothy Schacker, Irini Sereti, Russell P. Tracy

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

BACKGROUND: Persistent inflammation and incomplete immune recovery among persons with HIV (PHIV) are associated with increased disease risk. We hypothesized that the angiotensin receptor blocker (ARB) losartan would reduce inflammation by mitigating nuclear factor (NF)κB responses and promote T-cell recovery via inhibition of transforming growth factor-beta (TGFβ)-mediated fibrosis. METHODS: Losartan (100 mg) versus placebo over 12 months was investigated in a randomized (1 : 1) placebo-controlled trial, among PHIV age at least 50 years, receiving antiretroviral therapy (ART), with HIV RNA less than 200 copies/ml and CD4+ cell count 600 cells/μl or less. Inflammation, fibrosis and myocardial biomarkers were measured in blood using ELISA, electrochemiluminescence and immunoturbidimetric methods, and T-cell and monocyte phenotypes were assessed with flow cytometry among a subset of participants. Changes over follow-up in (log-2 transformed) biomarkers and cell phenotypes (untransformed) were compared between losartan and placebo arms using linear mixed models. RESULTS: Among 108 PHIV (n = 52 to losartan; n = 56 to placebo), 97% had a month 12 visit. Median age was 57 years and baseline CD4+ cell count was 408 cells/μl. Losartan treatment was not associated with an improvement in interleukin-6 levels, or other blood measures of inflammation, immune activation, fibrosis activity or myocardial function. CD4+ and CD8+ T cells also did not differ by treatment group. Losartan reduced SBP and DBP by 6 and 5 mmHg, respectively. CONCLUSION: Among older PHIV with viral suppression, losartan did not improve blood measures of inflammation nor T-cell immune recovery. Losartan treatment is unlikely to reduce inflammation associated comorbidities to a clinically meaningful degree, beyond the benefits from lowering blood pressure. CLINICALTRIALSGOV: NCT02049307.

Original languageEnglish (US)
Pages (from-to)575-583
Number of pages9
JournalAIDS (London, England)
Volume35
Issue number4
DOIs
StatePublished - Mar 15 2021

Bibliographical note

Funding Information:
This work was primarily supported by the National Institute of Allergy and Infectious Diseases (NIAID), NIH (grant number R21AI127149 to V. M.). Research data in this manuscript were collected, in part, as part of the Regional Prospective Observational Research for Tuberculosis (RePORT) India Consortium. This work was funded in whole or in part by federal funds from the DBT; the ICMR; the Office of AIDS Research, NIAID/NIH; CRDF Global; the NIH Baltimore-Washington-India Clinical Trials Unit for the NIAID Networks (grant number UM1AI069465 to A. G.); and the NIH (grant number R01AI097494 to J. E. G.).

Publisher Copyright:
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

PubMed: MeSH publication types

  • Journal Article
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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