Differential subcutaneous adipose tissue gene expression patterns in a randomized clinical trial of efavirenz or lopinavir-ritonavir in antiretroviral-naive patients

• Published in: Antimicrobial agents and chemotherapy Vol. 58; no. 11; pp. 6717 - 6723
• Main Authors: Egaña-Gorroño, L, Martínez, E, Domingo, P, Loncà, M, Escribà, T, Fontdevila, J, Vidal, F, Negredo, E, Gatell, J M, Arnedo, M
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.11.2014
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; Acquired Immunodeficiency Syndrome - virology; Adenine - analogs & derivatives; Adenine - therapeutic use; Adipogenesis; Adipogenesis - genetics; Adiponectin - biosynthesis; Adult; Anti-HIV Agents - therapeutic use; Antiviral Agents; Benzoxazines; Benzoxazines - therapeutic use; Body Composition; Body Composition - drug effects; CCAAT-Enhancer-Binding Proteins - biosynthesis; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Drug Combinations; Emtricitabine; Energy Metabolism - genetics; Female; Gene Expression; Glucose - metabolism; Glucose Transporter Type 4 - biosynthesis; HIV-1 - drug effects; Human immunodeficiency virus; Humans; Inflammation - genetics; Lipid Metabolism - genetics; Lipoprotein Lipase - genetics; Lopinavir; Lopinavir - therapeutic use; Male; Organophosphonates - therapeutic use; Reverse Transcriptase Inhibitors - therapeutic use; Ritonavir; Ritonavir - therapeutic use; Subcutaneous Fat; Subcutaneous Fat - cytology; Tenofovir
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.03481-14

Gene expression studies of subcutaneous adipose tissue may help to better understand the mechanisms behind body fat changes in HIV-infected patients who initiate antiretroviral therapy (ART). Here, we evaluated early changes in adipose tissue gene expression and their relationship to fat changes in ART-naive HIV-infected patients randomly assigned to initiate therapy with emtricitabine/tenofovir plus efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r). Patients had abdominal subcutaneous adipose tissue biopsies at baseline and week 16 and dual-energy-X-ray absorptiometry at baseline and weeks 16 and 48. mRNA changes of 11 genes involved in adipogenesis, lipid and glucose metabolism, mitochondrial energy, and inflammation were assessed through reverse transcription-quantitative PCR (RT-qPCR). Additionally, correlations between gene expression changes and fat changes were evaluated. Fat increased preferentially in the trunk with EFV and in the limbs with LPV/r (P < 0.05). After 16 weeks of exposure to the drug regimen, transcripts of CEBP/A, ADIPOQ, GLUT4, LPL, and COXIV were significantly down-regulated in the EFV arm compared to the LPV/r arm (P < 0.05). Significant correlations were observed between LPL expression change and trunk fat change at week 16 in both arms and between CEBP/A or COXIV change and trunk fat change at the same time point only in the EFV arm and not in the LPV/r arm. When combined with emtricitabine/tenofovir as standard backbone therapy, EFV and LPV/r induced differential early expression of genes involved in adipogenesis and energy metabolism. Moreover, these mRNA expression changes correlated with trunk fat change in the EFV arm. (This was a substudy of a randomized clinical trial [LIPOTAR study] registered at ClinicalTrials.gov under identifier NCT00759070.).