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The early effects of stavudine compared with tenofovir on adipocyte gene expression, mitochondrial DNA copy number and metabolic parameters in S outh A frican HIV ‐infected patients: a randomized trial
Author(s) -
Menezes CN,
Duarte R,
Dickens C,
DixPeek T,
Van Amsterdam D,
John MA,
Ive P,
Maskew M,
MacPhail P,
Fox MP,
Raal F,
Sanne I,
Crowther NJ
Publication year - 2013
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2012.01054.x
Subject(s) - stavudine , medicine , mitochondrial toxicity , efavirenz , lipid profile , lipoatrophy , pharmacology , lamivudine , immunology , toxicity , viral load , cholesterol , virus , hepatitis b virus , antiretroviral therapy
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 S outh A frica. 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 S outh A frican 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 mt DNA 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 < 0.05) and low‐dose stavudine ( P < 0.005) arms, respectively, when compared with TDF at 4 weeks. Nuclear respiratory factor‐1 ( NRF1 ) and mitochondrial cytochrome B ( MTCYB ) gene expression levels were affected by stavudine, with a significantly ( P < 0.05) greater fall in expression observed with the standard, but not the low dose compared with TDF . No significant differences were observed in markers of inflammation and lipid and glucose metabolism. Conclusions These results demonstrate early mitochondrial depletion among Black S outh A frican patients receiving low and standard doses of stavudine, with preservation of gene expression levels, except for NRF 1 and MTCYB , when compared with patients on TDF .