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.
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.
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司他夫定与替诺福韦相比对南非 HIV 感染者脂肪细胞基因表达、线粒体 DNA 拷贝数和代谢参数的早期影响：一项随机试验。
DOI：
10.1111/j.1468-1293.2012.01054.x
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发表时间：
2013
期刊：
影响因子：
3
通讯作者：
Crowther,NJ
中科院分区：
文献类型：
--
作者：
Menezes,CN;Duarte,R;Dickens,C;Dix-Peek,T;VanAmsterdam,D;John,M-A;Ive,P;Maskew,M;Macphail,P;Fox,MP;Raal,F;Sanne,I;Crowther,NJ
ObjectivesStavudine 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.MethodsSixty 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.ResultsA 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.ConclusionsThese results demonstrate early mitochondrial depletion among Black South African patients receiving low and standard doses of stavudine, with preservation of gene expression levels, except forNRF1andMTCYB, when compared with patients on TDF.
