Telmisartan therapy does not improve lymph node or adipose tissue fibrosis more than continued antiretroviral therapy alone

Netanya S. Utay, Douglas W. Kitch, Eunice Yeh, Carl J. Fichtenbaum, Michael M. Lederman, Jacob Estes, Claire Deleage, Clara Magyar, Scott D. Nelson, Karen L. Klingman, Barbara Bastow, Amneris E. Luque, Grace A. McComsey, Daniel C. Douek, Judith S. Currier, Jordan E. Lake

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background. Fibrosis in lymph nodes may limit CD4+ T-cell recovery, and lymph node and adipose tissue fibrosis may contribute to inflammation and comorbidities despite antiretroviral therapy (ART). We hypothesized that the angiotensin receptor blocker and peroxisome proliferator-activated receptor γ agonist telmisartan would decrease lymph node or adipose tissue fibrosis in treated human immunodeficiency virus type 1 (HIV) infection. Methods. In this 48-week, randomized, controlled trial, adults continued HIV–suppressive ART and received telmisartan or no drug. Collagen I, fibronectin, and phosphorylated SMAD3 (pSMAD3) deposition in lymph nodes, as well as collagen I, collagen VI, and fibronectin deposition in adipose tissue, were quantified by immunohistochemical analysis at weeks 0 and 48. Two-sided rank sum and signed rank tests compared changes over 48 weeks. Results. Forty-four participants enrolled; 35 had paired adipose tissue specimens, and 29 had paired lymph node specimens. The median change overall in the percentage of the area throughout which collagen I was deposited was −2.6 percentage points (P = 0.08) in lymph node specimens and −1.3 percentage points (P = .001) in adipose tissue specimens, with no between-arm differences. In lymph node specimens, pSMAD3 deposition changed by −0.5 percentage points overall (P = .04), with no between-arm differences. Telmisartan attenuated increases in fibronectin deposition (P = .06). In adipose tissue, changes in collagen VI deposition (−1.0 percentage point; P = .001) and fibronectin deposition (−2.4 percentage points; P < .001) were observed, with no between-arm differences. Conclusions. In adults with treated HIV infection, lymph node and adipose tissue fibrosis decreased with continued ART alone, with no additional fibrosis reduction with telmisartan therapy.

Original languageEnglish (US)
Pages (from-to)1770-1781
Number of pages12
JournalJournal of Infectious Diseases
Volume217
Issue number11
DOIs
StatePublished - Jun 1 2018

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Adipose Tissue
Fibrosis
Lymph Nodes
Collagen
Fibronectins
Virus Diseases
Therapeutics
HIV-1
Peroxisome Proliferator-Activated Receptors
telmisartan
Angiotensin Receptor Antagonists
Nonparametric Statistics
Comorbidity
Randomized Controlled Trials
Inflammation
T-Lymphocytes
Pharmaceutical Preparations

Keywords

  • Adipose tissue fibrosis
  • ART
  • HIV
  • Lymph node fibrosis
  • TGF-beta

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Telmisartan therapy does not improve lymph node or adipose tissue fibrosis more than continued antiretroviral therapy alone. / Utay, Netanya S.; Kitch, Douglas W.; Yeh, Eunice; Fichtenbaum, Carl J.; Lederman, Michael M.; Estes, Jacob; Deleage, Claire; Magyar, Clara; Nelson, Scott D.; Klingman, Karen L.; Bastow, Barbara; Luque, Amneris E.; McComsey, Grace A.; Douek, Daniel C.; Currier, Judith S.; Lake, Jordan E.

In: Journal of Infectious Diseases, Vol. 217, No. 11, 01.06.2018, p. 1770-1781.

Research output: Contribution to journalArticle

Utay, NS, Kitch, DW, Yeh, E, Fichtenbaum, CJ, Lederman, MM, Estes, J, Deleage, C, Magyar, C, Nelson, SD, Klingman, KL, Bastow, B, Luque, AE, McComsey, GA, Douek, DC, Currier, JS & Lake, JE 2018, 'Telmisartan therapy does not improve lymph node or adipose tissue fibrosis more than continued antiretroviral therapy alone', Journal of Infectious Diseases, vol. 217, no. 11, pp. 1770-1781. https://doi.org/10.1093/infdis/jiy064
Utay, Netanya S. ; Kitch, Douglas W. ; Yeh, Eunice ; Fichtenbaum, Carl J. ; Lederman, Michael M. ; Estes, Jacob ; Deleage, Claire ; Magyar, Clara ; Nelson, Scott D. ; Klingman, Karen L. ; Bastow, Barbara ; Luque, Amneris E. ; McComsey, Grace A. ; Douek, Daniel C. ; Currier, Judith S. ; Lake, Jordan E. / Telmisartan therapy does not improve lymph node or adipose tissue fibrosis more than continued antiretroviral therapy alone. In: Journal of Infectious Diseases. 2018 ; Vol. 217, No. 11. pp. 1770-1781.
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abstract = "Background. Fibrosis in lymph nodes may limit CD4+ T-cell recovery, and lymph node and adipose tissue fibrosis may contribute to inflammation and comorbidities despite antiretroviral therapy (ART). We hypothesized that the angiotensin receptor blocker and peroxisome proliferator-activated receptor γ agonist telmisartan would decrease lymph node or adipose tissue fibrosis in treated human immunodeficiency virus type 1 (HIV) infection. Methods. In this 48-week, randomized, controlled trial, adults continued HIV–suppressive ART and received telmisartan or no drug. Collagen I, fibronectin, and phosphorylated SMAD3 (pSMAD3) deposition in lymph nodes, as well as collagen I, collagen VI, and fibronectin deposition in adipose tissue, were quantified by immunohistochemical analysis at weeks 0 and 48. Two-sided rank sum and signed rank tests compared changes over 48 weeks. Results. Forty-four participants enrolled; 35 had paired adipose tissue specimens, and 29 had paired lymph node specimens. The median change overall in the percentage of the area throughout which collagen I was deposited was −2.6 percentage points (P = 0.08) in lymph node specimens and −1.3 percentage points (P = .001) in adipose tissue specimens, with no between-arm differences. In lymph node specimens, pSMAD3 deposition changed by −0.5 percentage points overall (P = .04), with no between-arm differences. Telmisartan attenuated increases in fibronectin deposition (P = .06). In adipose tissue, changes in collagen VI deposition (−1.0 percentage point; P = .001) and fibronectin deposition (−2.4 percentage points; P < .001) were observed, with no between-arm differences. Conclusions. In adults with treated HIV infection, lymph node and adipose tissue fibrosis decreased with continued ART alone, with no additional fibrosis reduction with telmisartan therapy.",
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T1 - Telmisartan therapy does not improve lymph node or adipose tissue fibrosis more than continued antiretroviral therapy alone

AU - Utay, Netanya S.

AU - Kitch, Douglas W.

AU - Yeh, Eunice

AU - Fichtenbaum, Carl J.

AU - Lederman, Michael M.

AU - Estes, Jacob

AU - Deleage, Claire

AU - Magyar, Clara

AU - Nelson, Scott D.

AU - Klingman, Karen L.

AU - Bastow, Barbara

AU - Luque, Amneris E.

AU - McComsey, Grace A.

AU - Douek, Daniel C.

AU - Currier, Judith S.

AU - Lake, Jordan E.

PY - 2018/6/1

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N2 - Background. Fibrosis in lymph nodes may limit CD4+ T-cell recovery, and lymph node and adipose tissue fibrosis may contribute to inflammation and comorbidities despite antiretroviral therapy (ART). We hypothesized that the angiotensin receptor blocker and peroxisome proliferator-activated receptor γ agonist telmisartan would decrease lymph node or adipose tissue fibrosis in treated human immunodeficiency virus type 1 (HIV) infection. Methods. In this 48-week, randomized, controlled trial, adults continued HIV–suppressive ART and received telmisartan or no drug. Collagen I, fibronectin, and phosphorylated SMAD3 (pSMAD3) deposition in lymph nodes, as well as collagen I, collagen VI, and fibronectin deposition in adipose tissue, were quantified by immunohistochemical analysis at weeks 0 and 48. Two-sided rank sum and signed rank tests compared changes over 48 weeks. Results. Forty-four participants enrolled; 35 had paired adipose tissue specimens, and 29 had paired lymph node specimens. The median change overall in the percentage of the area throughout which collagen I was deposited was −2.6 percentage points (P = 0.08) in lymph node specimens and −1.3 percentage points (P = .001) in adipose tissue specimens, with no between-arm differences. In lymph node specimens, pSMAD3 deposition changed by −0.5 percentage points overall (P = .04), with no between-arm differences. Telmisartan attenuated increases in fibronectin deposition (P = .06). In adipose tissue, changes in collagen VI deposition (−1.0 percentage point; P = .001) and fibronectin deposition (−2.4 percentage points; P < .001) were observed, with no between-arm differences. Conclusions. In adults with treated HIV infection, lymph node and adipose tissue fibrosis decreased with continued ART alone, with no additional fibrosis reduction with telmisartan therapy.

AB - Background. Fibrosis in lymph nodes may limit CD4+ T-cell recovery, and lymph node and adipose tissue fibrosis may contribute to inflammation and comorbidities despite antiretroviral therapy (ART). We hypothesized that the angiotensin receptor blocker and peroxisome proliferator-activated receptor γ agonist telmisartan would decrease lymph node or adipose tissue fibrosis in treated human immunodeficiency virus type 1 (HIV) infection. Methods. In this 48-week, randomized, controlled trial, adults continued HIV–suppressive ART and received telmisartan or no drug. Collagen I, fibronectin, and phosphorylated SMAD3 (pSMAD3) deposition in lymph nodes, as well as collagen I, collagen VI, and fibronectin deposition in adipose tissue, were quantified by immunohistochemical analysis at weeks 0 and 48. Two-sided rank sum and signed rank tests compared changes over 48 weeks. Results. Forty-four participants enrolled; 35 had paired adipose tissue specimens, and 29 had paired lymph node specimens. The median change overall in the percentage of the area throughout which collagen I was deposited was −2.6 percentage points (P = 0.08) in lymph node specimens and −1.3 percentage points (P = .001) in adipose tissue specimens, with no between-arm differences. In lymph node specimens, pSMAD3 deposition changed by −0.5 percentage points overall (P = .04), with no between-arm differences. Telmisartan attenuated increases in fibronectin deposition (P = .06). In adipose tissue, changes in collagen VI deposition (−1.0 percentage point; P = .001) and fibronectin deposition (−2.4 percentage points; P < .001) were observed, with no between-arm differences. Conclusions. In adults with treated HIV infection, lymph node and adipose tissue fibrosis decreased with continued ART alone, with no additional fibrosis reduction with telmisartan therapy.

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KW - TGF-beta

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