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

Author:

Cockerham, Leslie R

Yukl, Steven A

Harvill, Kara

Somsouk, Ma

Joshi, Sunil K

Sinclair, Elizabeth

Liegler, Teri

Hoh, Rebecca

Lyons, Sophie

Hunt, Peter W

Rupert, Adam

Sereti, Irini

Morcock, David

Rhodes, Ajantha

Emson, Claire

Hellerstein, Marc K

Estes, Jake

Lewin, Sharon

Deeks, Steven G

Hatano, Hiroyu
Author Address

Division of Infectious Diseases, Medical College of Wisconsin, Milwaukee, Wisconsin., Department of Medicine, San Francisco VA Medical Center, and University of California, San Francisco (UCSF), San Francisco, California., HIV, Infectious Diseases, and Global Medicine Division, San Francisco General Hospital, University of California, San Francisco, California., Division of Gastroenterology, San Francisco General Hospital, University of California, San Francisco, California., National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland., Frederick National Laboratory, Leidos Biomedical Research, Frederick, Maryland., Department of Infectious Diseases, The Alfred Hospital and Monash University, Melbourne, Victoria, Australia., Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia., Kinemed, Inc., Emeryville, California., Department of Nutritional Science and Toxicology, University of California, Berkeley, California.,

Abstract:

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. 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. 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. 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.

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Author Address