Effects of switching from stavudine to raltegravir on subcutaneous adipose tissue in HIV-infected patients with HIV/HAART-associated lipodystrophy syndrome (HALS). A clinical and molecular study

• Published in: PloS one Vol. 9; no. 2; p. e89088
• Main Authors: Domingo, Pere, Gutierrez, María del Mar, Gallego-Escuredo, José Miguel, Torres, Ferran, Mateo, Gracia María, Villarroya, Joan, de los Santos, Ignacio, Domingo, Joan Carles, Villarroya, Francesc, Del Rio, Luis, Estrada, Vicente, Giralt, Marta
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.02.2014; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adipocytes; Adiponectin; Adipose tissue; Adipose tissues; Adult; AIDS; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Antiretroviral drugs; Assaigs clínics; Biochemistry; Body Composition; Body fat; Body mass; CD4 antigen; Clinical trials; Cytochrome; Cytochrome b; DNA, Mitochondrial - metabolism; Drug therapy; Drugs; Dual energy X-ray absorptiometry; Exposure; Fasting; Female; Gene Expression; Genes; Highly active antiretroviral therapy; HIV; HIV (Viruses); HIV infections; HIV Infections - drug therapy; HIV patients; HIV tests; HIV-associated lipodystrophy syndrome; Hospitals; Human immunodeficiency virus; Humans; Infections; Infectious diseases; Insulin; Laboratory testing; Lipodystrophy; Lipodystrophy - chemically induced; Lipodystrophy - genetics; Male; Medical research; Medicaments; Medicine; Metabolism; Middle Aged; Mitochondria; Mitochondrial DNA; Molecular biology; Monocyte chemoattractant protein 1; Patients; Peroxisome proliferator-activated receptors; Pyrrolidinones - adverse effects; Pyrrolidinones - therapeutic use; Raltegravir Potassium; Relative abundance; Ribonucleic acid; RNA; Stavudine; Stavudine - adverse effects; Stavudine - therapeutic use; Subcutaneous Fat - drug effects; Subcutaneous Fat - metabolism; Switching; Síndrome de lipodistròfia associada a VIH; Teixit adipós; Tumor necrosis factor; VIH (Virus); Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0089088

HIV-1/HAART-associated lipodystrophy syndrome (HALS) has been associated with exposure to stavudine (d4T) through mitochondrial dysfunction. We performed a 48-week study to assess the effects of switching from d4T to raltegravir (RAL) on metabolic and fat molecular parameters of patients with HALS. Forty-two patients with HALS and a median exposure to d4T > 7 years were switched to RAL and followed for 48 weeks. Fasting metabolic tests, HIV RNA, CD4 cell count, and fat measured by DEXA were obtained at baseline and week 48. mtDNA and gene transcripts for PPAR gamma, adiponectin, cytochrome b, Cox IV, TNF alpha, MCP-1 and CD68 were assessed in paired subcutaneous fat tissue biopsies. Lipid parameters, fasting glucose, insulin, and HOMA-IR did not change significantly. Whole body fat (P = 0.0027) and limb fat mass (P<0.0001) increased from baseline. Trunk/limb fat ratio (P = 0.0022), fat mass ratio (P = 0.0020), fat mass index (P = 0.0011) and percent leg fat normalized to BMI (P<0.0001) improved after 48 weeks. Relative abundance of mtDNA, expression of PPAR gamma, adiponectin, Cyt b, and MCP-1 genes increased, whereas Cox IV, TNF alpha, and CD68 did not change significantly from baseline. Switching from d4T to RAL in patients with HALS is associated with an increase in limb fat mass and an improvement in markers of adipocyte differentiation and mitochondrial function in SAT.