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Cockerham LR, Yukl SA, Harvill K, et al. A Randomized Controlled Trial of Lisinopril to Decrease Lymphoid Fibrosis in Antiretroviral-Treated, HIV-infected Individuals. Pathog Immun. 2017;2(3):310-334doi: 10.20411/pai.v2i3.207.
Cockerham, L. R., Yukl, S. A., Harvill, K., Somsouk, M., Joshi, S. K., Sinclair, E., Liegler, T., Hoh, R., Lyons, S., Hunt, P. W., Rupert, A., Sereti, I., Morcock, D. R., Rhodes, A., Emson, C., Hellerstein, M. K., Estes, J. D., Lewin, S., Deeks, S. G., & Hatano, H. (2017). A Randomized Controlled Trial of Lisinopril to Decrease Lymphoid Fibrosis in Antiretroviral-Treated, HIV-infected Individuals. Pathogens & immunity, 2(3), 310-334. https://doi.org/10.20411/pai.v2i3.207
Cockerham, Leslie R, et al. "A Randomized Controlled Trial of Lisinopril to Decrease Lymphoid Fibrosis in Antiretroviral-Treated, HIV-infected Individuals." Pathogens & immunity vol. 2,3 (2017): 310-334. doi: https://doi.org/10.20411/pai.v2i3.207
Cockerham LR, Yukl SA, Harvill K, Somsouk M, Joshi SK, Sinclair E, Liegler T, Hoh R, Lyons S, Hunt PW, Rupert A, Sereti I, Morcock DR, Rhodes A, Emson C, Hellerstein MK, Estes JD, Lewin S, Deeks SG, Hatano H. A Randomized Controlled Trial of Lisinopril to Decrease Lymphoid Fibrosis in Antiretroviral-Treated, HIV-infected Individuals. Pathog Immun. 2017;2(3):310-334. doi: 10.20411/pai.v2i3.207. Epub 2017 Aug 02. PMID: 28936485; PMCID: PMC5604865.
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Pathog Immun. 2017;2(3):310-334. doi: 10.20411/pai.v2i3.207. Epub 2017 Aug 02.

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

Pathogens & immunity

Leslie R 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

Affiliations

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

PMID: 28936485 PMCID: PMC5604865 DOI: 10.20411/pai.v2i3.207

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.

Keywords: Anti-Inflammatory Agents/*therapeutic use; CD4 Lymphocyte Count; Disease Reservoirs/*virology; HIV; Immunology; Lymphoid fibrosis; T-cell activation

Conflict of interest statement

POTENTIAL CONFLICTS OF INTEREST Potential conflicts of interest: H.H. received research support from Merck. Both raltegravir and placebo pills were provided by Merck. For the remaining authors no conf

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