Altered subcutaneous adipose tissue parameters after switching ART-controlled HIV+ patients to raltegravir/maraviroc.

OBJECTIVE 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. DESIGN Substudy of ROCnRAL-ANRS157 with investigation of subcutaneous abdominal adipose tissue (SCAT) biopsy at inclusion and study end. METHODS 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 Wilcoxon-paired test. RESULTS The patients (n = 8) were mainly male (7/8), aged (mean±SEM) 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). Amongst the 16,094 RNA transcripts, 458 genes were up-regulated and 244 down-regulated. Analyses of the KEGG and GO 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. CONCLUSION 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, immune activation/inflammation profile was globally lowered. We propose that raltegravir/maraviroc might favor SCAT gain but reduce inflammation/immune activation.