Adipose tissue transcriptome in patients switching efavirenz or a protease inhibitor to raltegravir compared to people without HIV.

Abstract

Objective: To study the subcutaneous adipose tissue (SAT) transcriptome in people with HIV (PWH) switching efavirenz (EFV) or a protease inhibitor (PI) to raltegravir and to compare the transcriptome of PWH to those of people without HIV (PWoH).

Design: PWH (n = 36) on EFV (n = 22) or a PI (n = 14) based ART regimen were randomized to switch to RAL (n = 15) or to continue unchanged medication (n = 17). PWoH (n = 10), comparable in age and body mass index, were included for comparison.

Methods: SAT gene expression was analyzed via RNA sequencing (Illumina Stranded mRNA library prep).

Results: At baseline, only 51 out of 19930 genes showed differential expression (FDR <0.05) between PWH and PWoH. Differentially expressed genes in PWH were identified as being HIV host factors or were associated with immune response, lipid metabolism, adipogenesis, apoptosis regulation, DNA/RNA metabolism, and cell structures. Mitochondria-encoded genes were consistently downregulated in PWH. Intergroup variations among PWH using different ART (EFV, PI, RAL) were not significant, and switching EFV or a PI to RAL did not induce substantial changes in the SAT transcriptome.

Conclusions: While some specific genes linked to HIV are differentially expressed in PWH compared to PWoH, the overall SAT transcriptome remains relatively stable across various antiretroviral treatments and upon switching from EFV/PI to RAL. These findings enhance our understanding of the molecular landscape on SAT in the context of HIV and ART.