A Randomized Controlled Trial of Lisinopril to Decrease Lymphoid Fibrosis in Antiretroviral-Treated, HIV-infected Individuals

Main Article Content

Leslie Renee Cockerham
Steven A. Yukl
Kara Harvill
Ma Somsouk
Sunil K. Joshi
Elizabeth Sinclair
Teri Liegler
Rebecca Hoh
Sophie Lyons
Peter W. Hunt
Adam Rupert
Irini Sereti
David R. Morcock
Ajantha Rhodes
Claire Emson
Marc K. Hellerstein
Jacob D. Estes
Sharon Lewin
Steven G. Deeks
Hiroyu Hatano

Abstract

Background: In HIV infection, lymphoid tissue is disrupted by fibrosis. Angiotensin converting enzyme inhibitors have anti-fibrotic properties. We completed a pilot study to assess whether the addition of lisinopril to antiretroviral therapy (ART) reverses fibrosis of gut tissue, and whether this leads to reduction of HIV RNA and DNA levels.

Methods: Thirty HIV-infected individuals on ART were randomized to lisinopril at 20mg daily or matching placebo for 24 weeks. All participants underwent rectal biopsies prior to starting the study drug and at 22 weeks, and there were regular blood draws. The primary end point was the change in HIV RNA and DNA levels in rectal tissue. Secondary outcomes included the change in 1) HIV levels in blood; 2) Gag-specific T-cell responses; 3) levels of T-cell activation; and 4) collagen deposition.

Results: The addition of lisinopril did not have a significant effect on the levels of HIV RNA or DNA in gut tissue or blood, Gag-specific responses, or levels of T-cell activation. Lisinopril also did not have a significant impact on lymphoid fibrosis in the rectum, as assessed by quantitative histology or heavy water labeling.

Conclusions: Treatment with lisinopril for 24 weeks in HIV-infected adults did not have an effect on lymphoid fibrosis, immune activation, or gut tissue viral reservoirs. Further study is needed to see if other anti-fibrotic agents may be useful in reversing lymphoid fibrosis and reducing HIV levels.

Clinical Trials Registration: NCT01535235

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Article Details

Section
Articles
Author Biography

Leslie Renee Cockerham, Medical College of Wisconsin

Assistant Professor of Medicine
Division of Infectious Diseases

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