Altered subcutaneous adipose tissue parameters after switching ART-controlled HIV+ patients to raltegravir/maraviroc.
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
01 08 2021
01 08 2021
Historique:
pubmed:
9
4
2021
medline:
7
8
2021
entrez:
8
4
2021
Statut:
ppublish
Résumé
To evaluate the effect on anthropometric, metabolic and adipose tissue parameters of switching ART-controlled persons living with HIV (PLWH) from a protease inhibitor regimen to raltegravir/maraviroc. Sub-study of the ANRS157 ROCnRAL study with the investigation of subcutaneous abdominal adipose tissue (SCAT) biopsy at inclusion and study end. We performed lipoaspiration of paired SCAT samples, histology on fresh/fixed samples and examined the transcriptomic profile analyzed using Illumina microarrays after RNA extraction. Statistical analyses used the Wilcoxon-paired test. The patients (n = 8) were mainly male (7/8), aged (mean ± standard error of the mean) 54.9 ± 1.2 years, BMI 26.1 ± 1.2 kg/m2, CD4+ 699 ± 56 cells/mm3, all viral load (VL) <50 copies/ml. After a follow-up of 6 ± 0.5 months, all PLWH remained with VL <50 copies/ml. BMI, trunk and limb fat amounts were unchanged yet systemic insulin resistance increased. Adipose tissue histology was unchanged except for borderline increased adipocyte diameter (P = 0.1). Among the 16 094 RNA transcripts, 458 genes were up-regulated and 244 were down-regulated. Analyses of the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases, evaluating modifications in the main functional pathways, revealed that genes related to immune recognition/function were less expressed as were genes encoding T-cell receptor and receptor signaling pathways. The gene expression profiles indicated decreased inflammation but genes involved in adipogenesis and insulin resistance were overexpressed. After 6 months of raltegravir/maraviroc, adipogenesis-related gene profile was enhanced in SCAT, in agreement with a tendency for increased adipocyte size. Enhanced SCAT insulin resistance-related profile was concordant with higher systemic insulin resistance. However, the immune activation/inflammation profile was globally lowered. We propose that raltegravir/maraviroc might favor SCAT gain but reduce inflammation/immune activation.
Identifiants
pubmed: 33831906
doi: 10.1097/QAD.0000000000002900
pii: 00002030-202108010-00011
doi:
Substances chimiques
Anti-HIV Agents
0
Raltegravir Potassium
43Y000U234
Maraviroc
MD6P741W8A
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1625-1630Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Références
Koethe JR, Lagathu C, Lake JE, Domingo P, Calmy A, Falutz J, et al. HIV and antiretroviral therapy-related fat alterations . Nat Rev Dis Primers 2020; 6:48doi: 10.1038/s41572-020-0181-1.
doi: 10.1038/s41572-020-0181-1
Gorwood J, Bourgeois C, Pourcher V, Pourcher G, Charlotte F, Mantecon M, et al. The integrase inhibitors dolutegravir and raltegravir exert pro-adipogenic and profibrotic effects and induce insulin resistance in human/simian adipose tissue and human adipocytes . Clin Infect Dis 2020; 71:549–560.
Katlama C, Assoumou L, Valantin MA, Soulie C, Duvivier C, Chablais L, et al. Maraviroc plus raltegravir failed to maintain virological suppression in HIV-infected patients with lipohypertrophy: results from the ROCnRAL ANRS 157 study . J Antimicrob Chemother 2014; 69:1648–1652.
Martinez E, D’Albuquerque PM, Llibre JM, Gutierrez F, Podzamczer D, Antela A, et al. Changes in cardiovascular biomarkers in HIV-infected patients switching from ritonavir-boosted protease inhibitors to raltegravir . AIDS 2012; 26:2315–2326.
Katlama C, Assoumou L, Valantin MA, Soulie C, Martinez E, Beniguel L, et al. Dual therapy combining raltegravir with etravirine maintains a high level of viral suppression over 96 weeks in long-term experienced HIV-infected individuals over 45 years on a PI-based regimen: results from the Phase II ANRS 163 ETRAL study . J Antimicrob Chemother 2019; 74:2742–2751.
Gatell JM, Assoumou L, Moyle G, Waters L, Johnson M, Domingo P, et al. Immediate versus deferred switching from a boosted protease inhibitor-based regimen to a dolutegravir-based regimen in virologically suppressed patients with high cardiovascular risk or age ≥50 years: final 96-week results of the NEAT022 study . Clin Infect Dis 2019; 68:597–606.
Assoumou L, di Clemente N, Fellahi S, Beniguel L, Bastard JP, Feve B, et al. Impact of the reproductive/hormonal status on weight, fat and insulin resistance in HIV-infected women switching from a PI regimen to dual raltegravir-etravirine therapy: results from the ANRS163-ETRAL trial at 48 and 96 weeks . HIV Med 2019; 20:132.
Francisci D, Pirro M, Schiaroli E, Mannarino MR, Cipriani S, Bianconi V, et al. Maraviroc intensification modulates atherosclerotic progression in HIV-suppressed patients at high cardiovascular risk. A randomized, crossover pilot study . Open Forum Infect Dis 2019; 6:ofz112doi: 10.1093/ofid/ofz112.
doi: 10.1093/ofid/ofz112
Piconi S, Pocaterra D, Rainone V, Cossu M, Masetti M, Rizzardini G, et al. Maraviroc reduces arterial stiffness in PI-treated HIV-infected patients . Sci Rep 2016; 6:28853doi: 10.1038/srep28853.
doi: 10.1038/srep28853
Gonzalez EO, Boix V, Deltoro MG, Aldeguer JL, Portilla J, Montero M, et al. The effects of Maraviroc on liver fibrosis in HIV/HCV co-infected patients . J Int AIDS Soc 2014; 17: (Suppl 3): 19643doi: 10.7448/ias.17.4.19643.
doi: 10.7448/ias.17.4.19643
Bradshaw D, Gilleece Y, Verma S, Abramowicz I, Bremner S, Perry N. Protocol for a phase IV, open-label feasibility study investigating noninvasive markers of hepatic fibrosis in people living with HIV-1 and nonalcoholic fatty liver disease randomised to receiving optimised background therapy (OBT) plus maraviroc or OBT alone . BMJ Open 2020; 10:e035596.
Bastard JP, Fellahi S, Couffignal C, Raffi F, Gras G, Hardel L, et al. Increased systemic immune activation and inflammatory profile of long-term HIV-infected ART-controlled patients is related to personal factors, but not to markers of HIV infection severity . J Antimicrob Chemother 2015; 70:1816–1824.
Gorwood J, Bourgeois C, Mantecon M, Atlan M, Pourcher V, Pourcher G, et al. Impact of HIV/simian immunodeficiency virus infection and viral proteins on adipose tissue fibrosis and adipogenesis . AIDS 2019; 33:953–964.
Lacroix D, Moutel S, Coupaye M, Huvenne H, Faucher P, Pelloux V, et al. Metabolic and adipose tissue signatures in adults with Prader-Willi syndrome: a model of extreme adiposity . J Clin Endocrinol Metab 2015; 100:850–859.
Rabasa-Lhoret R, Bastard JP, Jan V, Ducluzeau P, Andreelli F, Guerbre F, et al. Modified quantitative insulin sensitivity check index is better correlated to hyperinsulinemic glucose clamp than other fasting-based index of insulin sesnitivity in different insulin-resistant states . J Clin Endocrinol Metab 2003; 88:4917–4923.
Diaz-Delfin J, Domingo P, Giralt M, Villarroya F. Maraviroc reduces cytokine expression and secretion in human adipose cells without altering adipogenic differentiation . Cytokine 2013; 61:808–815.
Pourcher V, Dutoit Y, Capeau J, Boccara F, Soulie C, Ndoadoumgue A, et al. Characteristics of HIV+ and HIV– patients undergoing bariatric surgery: ObeVIH study. In: Virtual CROI scientific spotlight-TM ID1717. Virtual CROI scientific spotlights #511, 2021.
Guaraldi G, Draisci J, Milic J, Carli F, Besutti G, Bassoli C, et al. Fat distribution and density in people living with HIV with ≥5% weight gain . J Intern AIDS Soc 2020; 23 (S7):E25616.
Perez-Matute P, Pichel JG, Iniguez M, Recio-Fernandez E, Perez-Martinez L, Torrens R, et al. Maraviroc ameliorates the increased adipose tissue macrophage recruitment induced by a high-fat diet in a mouse model of obesity . Antivir Ther 2017; 22:163–168.
Auclair M, Guenantin AC, Fellahi S, Garcia M, Capeau J. HIV antiretroviral drugs, dolutegravir, maraviroc and ritonavir-boosted atazanavir use different pathways to affect inflammation, senescence and insulin sensitivity in human coronary endothelial cells . PLoS One 2020; 15:e0226924doi: 10.1371/journal.pone.0226924.
doi: 10.1371/journal.pone.0226924
Assoumou L, Racine C, Fellahi S, Lamaziere A, Farabos D, Beniguel L, et al. Fat gain differs by sex and hormonal status in persons living with suppressed HIV switched to raltegravir/etravirine . AIDS 2020; 34:1859–1862.
Divoux A, Tordjman J, Lacasa D, Veyrie N, Hugol D, Aissat A, et al. Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss . Diabetes 2010; 59:2817–2825.
Martinez E, Assoumou L, Moyle G, Waters L, Johnson M, Domingo P, et al. 48-week changes in biomarkers in subjects with high cardiovascular risk boosted switching from ritonavir-protease inhibitors to dolutegravir: the NEAT022 study . J Int AIDS Soc 2018; 21 (S8):e25187.