The early effects of stavudine compared with tenofovir on adipocyte gene expression, mitochondrial DNA copy number and metabolic parameters in South African HIV‐infected patients: a randomized trial

• Published in: HIV medicine 2013-04, Vol.14 (4), p.217-225
• Main Authors: Menezes, CN, Duarte, R, Dickens, C, Dix‐Peek, T, Van Amsterdam, D, John, M‐A, Ive, P, Maskew, M, MacPhail, P, Fox, MP, Raal, F, Sanne, I, Crowther, NJ
• Format: Article
• Language: English
• Subjects: Adenine - analogs & derivatives; Adenine - therapeutic use; Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; Adult; Anti-HIV Agents - therapeutic use; Antiretroviral Therapy, Highly Active; Biomarkers - metabolism; DNA Copy Number Variations - drug effects; DNA, Mitochondrial - drug effects; DNA, Mitochondrial - genetics; Dose-Response Relationship, Drug; Female; gene expression; Gene Expression Profiling; Glucose - metabolism; HIV Infections - drug therapy; HIV Infections - genetics; HIV Infections - metabolism; Human immunodeficiency virus; Humans; Inflammation - metabolism; insulin resistance; Lipid Metabolism - drug effects; lipids; Male; Middle Aged; mitochondria; Organophosphonates - therapeutic use; Prospective Studies; Reverse Transcriptase Inhibitors - therapeutic use; South Africa; stavudine; Stavudine - therapeutic use; Tenofovir
• ISSN: 1464-2662; 1468-1293
• DOI: 10.1111/j.1468-1293.2012.01054.x

Objectives Stavudine is being phased out because of its mitochondrial toxicity and tenofovir (TDF) is recommended as part of first‐line highly active antiretroviral therapy (HAART) in South Africa. A prospective, open‐label, randomized controlled trial comparing standard‐ and low‐dose stavudine with TDF was performed to assess early differences in adipocyte mtDNA copy number, gene expression and metabolic parameters in Black South African HIV‐infected patients. Methods Sixty patients were randomized 1:1:1 to either standard‐dose (30–40 mg) or low‐dose (20–30 mg) stavudine or TDF (300 mg) each combined with lamivudine and efavirenz. Subcutaneous fat biopsies were obtained at weeks 0 and 4. Adipocyte mtDNA copies/cell and gene expression were measured using quantitative polymerase chain reaction (qPCR). Markers of inflammation and lipid and glucose metabolism were also assessed. Results A 29% and 32% decrease in the mean mtDNA copies/cell was noted in the standard‐dose (P