Abstract P01
Antiviral Therapy 2019; 24 Suppl 1:A37
Subcutaneous adipose tissue modifications induced by a switch to dual raltegravir-maraviroc therapy in controlled HIV-infected patients: a sub-study of the ANRS-ROCnRAL157 clinical trial
J-P Bastard
1
, V Pelloux
2
, R Alili
2
, S Fellahi
1
, J Aron-Wisnewsky
2
, L Assoumou
3
, E Prifti
4
, C Katlama
3
, K Clément
2
,
J Capeau
1
1Faculty of Medicine, Sorbonne University, Inserm UMR_S938, CRSA, ICAN, Paris, France; 2Faculty of Medicine, Sorbonne University, Inserm UMR_S1269, NutrOmics, ICAN, Paris, France; 3Faculty of Medicine, Sorbonne University, Inserm UMR_S1136, IPLESP, Department of Infectious Diseases, Pitié-Salpétrière Hospital, APHP, Paris, France; 4IHU ICAN, Paris, France
Objectives: Integrase inhibitors including raltegravir have been associated with weight/fat gain. The mechanisms involved remain unknown. The ROCnRAL study enrolled suppressed HIV-infected patients with central fat accumulation switched to maraviroc/raltegravir. Herein, we analysed the effects of this switch on metabolic modifications and subcutaneous abdominal adipose tissue (scAT) transcriptome.
Material and methods: In eight patients, paired scAT samples, withdrawn by needle aspiration at inclusion and the end of the study, were available. We extracted total mRNA and examined the transcriptomic profile using Illumina microarrays, as well as scAT adipocyte size.
Results: All patients were male, aged 55 ±3 y (mean ±sd), BMI=26.1 kg/m2, waist circumference =94.6 cm, HOMA-IR=2.4. After a mean follow-up of 25 weeks, BMI increased to 26.4 kg/m2 (P=0.01), HOMA-IR to 6.7 (P=0.05) and adipocyte size to 113 microns (P=0.09). In the 16 paired samples, we identified 16,094 variants: 458 genes were up-regulated with a fold-change of 10.6-1.1 while 244 genes were down-regulated with a fold-change of 0.66-0.9. We further examined the functional changes that characterized this transcriptomic profile using KEGG data base. The most enriched function (19.4%) was ubiquitin-mediated proteolysis. Functions related to apoptosis were also enriched. Moreover, the main impoverished functions (29.7%) were related to ribosomes, followed by functions related to cell adhesion, grouping genes involved into immune cell recognition (27%), and functions involved into immune-related diseases (10.8%) suggesting a major reduction of scAT immune function/ activation. While IL25, IL7R, CD247, CD3D and CD58 gene expression was decreased, that of IL10 and IL18 was increased.
Conclusions: In eight controlled HIV-infected patients with central fat accumulation switching to raltegravir/ maraviroc resulted in major modification of adipocyte size and transcriptomic pattern. Overall, function related to protein degradation and apoptosis were increased and to protein synthesis decreased. Immune-related genes were mainly decreased. Further investigation is required to examine the link between these modifications and raltegravir-associated weight/fat gain.
