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

11 Scopus citations


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 (100mg) 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 200copies/ml and CD4+cell count 600cells/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 408cells/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 5mmHg, 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.ClinicalTrials.gov:NCT02049307.

Original languageEnglish (US)
Pages (from-to)575-583
Number of pages9
Issue number4
StatePublished - Mar 15 2021

Bibliographical note

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© 2021 Lippincott Williams and Wilkins. All rights reserved.


  • HIV
  • ageing
  • comorbidities
  • fibrosis
  • immune recovery
  • inflammation


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