Antiretroviral Therapy Initiation Is Associated With Decreased Visceral and Subcutaneous Adipose Tissue Density in People Living With Human Immunodeficiency Virus.
HIV
antiretroviral therapy
fat density
fat gain
inflammatory biomarkers
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
15 03 2021
15 03 2021
Historique:
received:
14
11
2019
accepted:
25
02
2020
pubmed:
29
2
2020
medline:
29
4
2021
entrez:
29
2
2020
Statut:
ppublish
Résumé
Adipose tissue (AT) alterations are common in people living with human immunodeficiency virus (PLWH). Decreases in AT density suggest disrupted adipocyte function/hypertrophy. We assessed changes in AT density after antiretroviral therapy (ART) initiation and associations with immunometabolic parameters. In a prospective randomized clinical trial of ART initiation, L4-L5 abdominal CT scans measured subcutaneous AT (SAT) and visceral AT (VAT) area and density in treatment-naive PLWH randomized to tenofovir-emtricitabine plus ritonavir-boosted atazanavir, ritonavir-boosted darunavir, or raltegravir. Linear regression models compared week 0 and week 96 levels, and 96-week changes, in SAT and VAT density (in Hounsfield units [HU]). Spearman correlations assessed relationships between AT density and immunometabolic parameters. Of the 228 participants, 89% were male and 44% were white non-Hispanic. Median age was 36 years, baseline HIV-1 RNA was 4.6 log10 copies/mL, and CD4+ T-cell count was 344 cells/μL. Over 96 weeks, SAT and VAT HU decreased significantly in all arms. Less dense week 96 SAT and VAT density correlated with higher high-density lipoprotein (HDL) cholesterol and adiponectin (r = 0.19-0.30) levels and lower interleukin 6, non-HDL cholesterol, triglyceride, leptin, and homeostatic model assessment of insulin resistance (r = -0.23 to -0.68) levels at week 96 after adjusting for baseline CD4+ T-cell count, HIV-1 RNA, and baseline AT area. Following virologic suppression, lower SAT and VAT density was associated with greater plasma measures of systemic inflammation, lipid disturbances, and insulin resistance independent of AT area, suggesting that changes in AT density with ART may lead to adverse health outcomes independent of AT quantity. NCT00851799.
Sections du résumé
BACKGROUND
Adipose tissue (AT) alterations are common in people living with human immunodeficiency virus (PLWH). Decreases in AT density suggest disrupted adipocyte function/hypertrophy. We assessed changes in AT density after antiretroviral therapy (ART) initiation and associations with immunometabolic parameters.
METHODS
In a prospective randomized clinical trial of ART initiation, L4-L5 abdominal CT scans measured subcutaneous AT (SAT) and visceral AT (VAT) area and density in treatment-naive PLWH randomized to tenofovir-emtricitabine plus ritonavir-boosted atazanavir, ritonavir-boosted darunavir, or raltegravir. Linear regression models compared week 0 and week 96 levels, and 96-week changes, in SAT and VAT density (in Hounsfield units [HU]). Spearman correlations assessed relationships between AT density and immunometabolic parameters.
RESULTS
Of the 228 participants, 89% were male and 44% were white non-Hispanic. Median age was 36 years, baseline HIV-1 RNA was 4.6 log10 copies/mL, and CD4+ T-cell count was 344 cells/μL. Over 96 weeks, SAT and VAT HU decreased significantly in all arms. Less dense week 96 SAT and VAT density correlated with higher high-density lipoprotein (HDL) cholesterol and adiponectin (r = 0.19-0.30) levels and lower interleukin 6, non-HDL cholesterol, triglyceride, leptin, and homeostatic model assessment of insulin resistance (r = -0.23 to -0.68) levels at week 96 after adjusting for baseline CD4+ T-cell count, HIV-1 RNA, and baseline AT area.
CONCLUSIONS
Following virologic suppression, lower SAT and VAT density was associated with greater plasma measures of systemic inflammation, lipid disturbances, and insulin resistance independent of AT area, suggesting that changes in AT density with ART may lead to adverse health outcomes independent of AT quantity.
CLINICAL TRIALS REGISTRATION
NCT00851799.
Identifiants
pubmed: 32107532
pii: 5763206
doi: 10.1093/cid/ciaa196
pmc: PMC7958728
doi:
Substances chimiques
Anti-HIV Agents
0
Banques de données
ClinicalTrials.gov
['NCT00851799']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
979-986Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI106701
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069471
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068634
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG054366
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK048520
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069424
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI068634
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068636
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Références
Eur J Immunol. 2017 Dec;47(12):2113-2123
pubmed: 28762530
AIDS Care. 2011 Aug;23(8):929-38
pubmed: 21767228
J Clin Endocrinol Metab. 2007 Mar;92(3):1023-33
pubmed: 17164304
Diabetes. 2010 Nov;59(11):2817-25
pubmed: 20713683
Antivir Ther. 2006;11(6):729-40
pubmed: 17310817
J Clin Endocrinol Metab. 2009 Dec;94(12):5155-62
pubmed: 19837927
Antivir Ther. 2012;17(3):529-40
pubmed: 22301094
Am J Clin Nutr. 2008 Jan;87(1):56-63
pubmed: 18175737
J Acquir Immune Defic Syndr. 2017 Dec 15;76(5):527-531
pubmed: 28825943
J Clin Endocrinol Metab. 2019 Oct 1;104(10):4857-4864
pubmed: 31329901
J Nucl Med. 2010 Feb;51(2):246-50
pubmed: 20124047
Circulation. 2007 Jul 3;116(1):39-48
pubmed: 17576866
J Acquir Immune Defic Syndr. 2007 Dec 1;46(4):451-5
pubmed: 18077834
Expert Rev Cardiovasc Ther. 2008 Mar;6(3):343-68
pubmed: 18327995
AIDS. 2009 Jun 1;23(9):1109-18
pubmed: 19417580
Clin Infect Dis. 2015 Aug 15;61(4):651-60
pubmed: 25904376
J Infect Dis. 2011 Jun 15;203(12):1824-31
pubmed: 21606541
J Gerontol A Biol Sci Med Sci. 2014 Jan;69(1):109-17
pubmed: 23707956
Sci Transl Med. 2013 Nov 27;5(213):213ra164
pubmed: 24285483
AIDS. 2015 Sep 10;29(14):1775-83
pubmed: 26372383
JACC Cardiovasc Imaging. 2013 Jul;6(7):762-71
pubmed: 23664720
J Am Heart Assoc. 2016 Feb 29;5(3):e002545
pubmed: 26927600
Clin Infect Dis. 2020 Dec 3;71(9):e471-e477
pubmed: 32099991
Curr HIV Res. 2011 Apr;9(3):174-9
pubmed: 21585335
Best Pract Res Clin Endocrinol Metab. 2011 Jun;25(3):487-99
pubmed: 21663842
J Clin Endocrinol Metab. 2012 Feb;97(2):E183-92
pubmed: 22162470
Metabolism. 2018 Jan;78:118-127
pubmed: 29051043
Antiviral Res. 2018 Jun;154:140-148
pubmed: 29630975
Nutrition. 2012 Feb;28(2):113-7
pubmed: 22208553
J Am Coll Cardiol. 2016 Oct 4;68(14):1509-21
pubmed: 27687192
J Am Heart Assoc. 2014 Aug 28;3(4):
pubmed: 25169793
Nat Rev Immunol. 2006 Oct;6(10):772-83
pubmed: 16998510
AIDS. 2011 Jul 17;25(11):1405-14
pubmed: 21572308
ISRN Inflamm. 2013 Dec 22;2013:139239
pubmed: 24455420
J Antimicrob Chemother. 2018 Aug 1;73(8):2177-2185
pubmed: 29722811
AIDS. 2017 Aug 24;31(13):1831-1838
pubmed: 28590329
Obesity (Silver Spring). 2014 Mar;22(3):691-7
pubmed: 23804589
Clin Infect Dis. 2016 Apr 1;62(7):853-62
pubmed: 26797215
Open Forum Infect Dis. 2017 Nov 03;4(4):ofx239
pubmed: 29255735
Int J Obes. 1987;11(2):129-40
pubmed: 3610466
Diabetes. 2007 Apr;56(4):1010-3
pubmed: 17287468
AIDS. 2004 Jan 23;18(2):189-98
pubmed: 15075535
Obesity (Silver Spring). 2016 Feb;24(2):499-505
pubmed: 26694629