Miller Robert F, Shahmonesh Maryam, Hanna Michael G, Unwin Robert J, Schapira Anthony H V, Weller Ian V D
Department of Sexually Transmitted Diseases, Royal Free and University College Medical School, University College London and Camden Primary Care Trust, London, UK.
Antivir Ther. 2003 Jun;8(3):253-7.
An HIV-infected man taking long-term zidovudine and didanosine presented with a polyphenotypic expression of nucleoside reverse transcriptase inhibitor (NRTI)-induced mitochondrial toxicity. Clinical features included lactic acidosis, myopathy, Fanconi-type proximal tubulopathy, pancreatic dysfunction, pseudo-obstruction, mega-oesophagus, peripheral sensory neuropathy and osteoporosis. A muscle biopsy showed morphologically abnormal mitochondria and respiratory chain biochemistry revealed marked reductions in the activity of respiratory chain enzymes containing mitochondrial DNA-encoded subunits. Southern blotting showed no mitochondrial DNA depletion and long PCR revealed only minor deletions. Following withdrawal of NRTI therapy, the lactic acidosis, pancreatic dysfunction and Fanconi's tubulopathy rapidly improved. Over the next 6 months there was marked improvement in osteoporosis, myopathy and neuropathy. At this stage, dual protease inhibitors and nevirapine were started. A repeat muscle biopsy 14 months after presentation showed normal morphology and respiratory chain biochemistry was almost normal.
一名长期服用齐多夫定和去羟肌苷的艾滋病毒感染男性出现了核苷类逆转录酶抑制剂（NRTI）诱导的线粒体毒性的多表型表现。临床特征包括乳酸酸中毒、肌病、范科尼型近端肾小管病、胰腺功能障碍、假性肠梗阻、巨食管、周围感觉神经病变和骨质疏松症。肌肉活检显示线粒体形态异常，呼吸链生化分析显示含有线粒体DNA编码亚基的呼吸链酶活性显著降低。Southern印迹法显示线粒体DNA无消耗，长链PCR仅显示少量缺失。停用NRTI治疗后，乳酸酸中毒、胰腺功能障碍和范科尼肾小管病迅速改善。在接下来的6个月里，骨质疏松症、肌病和神经病变有明显改善。此时，开始使用双重蛋白酶抑制剂和奈韦拉平。发病14个月后重复进行肌肉活检，结果显示形态正常，呼吸链生化分析几乎正常。
