Department of Internal Medicine, St Josef-Hospital, Ruhr-University of Bochum, Bochum, Germany.
HIV Med. 2011 Jan;12(1):40-5. doi: 10.1111/j.1468-1293.2010.00847.x.
Uncontrolled viral replication and antiretroviral treatment (ART) may independently contribute to hepatic mitochondrial toxicity. The present study was designed to explore the longitudinal effects of treatment modifications on hepatic mitochondrial function by means of noninvasive (13) C-methionine breath test (MeBT) diagnostics.
A total of 113 HIV-infected patients underwent two consecutive MeBTs over an interval of 11.8±3.5 months. Forty-nine patients remained on stable ART or no therapy; 28 participants switched ART; 27 patients (re)initiated ART, and nine individuals underwent a structured treatment interruption (STI) of ART between MeBTs 1 and 2. Breath test results were expressed as cumulative percentage dose of (13) CO(2) recovered after 1.5 h test time (cPDR(1.5h) ).
Initiation of ART in treatment-naïve individuals and patients on STI was associated with a significant improvement of hepatic mitochondrial function (P<0.05). Cessation of ART or a prolonged delay in initiating therapy in treatment-naïve patients in turn led to a significant decline of (13) C-exhalation compared with baseline (P<0.05). A marked increase in (13) C-exhalation was observed in individuals who switched from stavudine or ddI to tenofovir or abacavir (+170%; P<0.001), while no differences between MeBTs 1 and 2 were found in individuals on ART who had remained on stable regimens or in those who changed a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) component.
The present data suggest that hepatic mitochondrial function in HIV disease is a dynamic process with a high regenerative capacity and highlight the pathogenic relevance of HIV replication. Our findings suggest that modern ART per se does not negatively impact hepatic mitochondrial function.
病毒复制失控和抗逆转录病毒治疗（ART）可能独立导致肝线粒体毒性。本研究旨在通过非侵入性（13）C-蛋氨酸呼吸试验（MeBT）诊断来探索治疗方案改变对肝线粒体功能的纵向影响。
共有 113 名 HIV 感染患者在 11.8±3.5 个月的间隔内连续进行了两次 MeBT。49 名患者继续接受稳定的 ART 或无治疗；28 名参与者切换了 ART；27 名患者（重新）开始接受 ART，9 名患者在 MeBT1 和 MeBT2 之间进行了结构化治疗中断（STI）。呼吸试验结果表示为 1.5 小时测试时间后（13）CO2 回收的累积剂量百分比（cPDR（1.5h））。
在治疗初治患者和接受 STI 的患者中开始 ART 与肝线粒体功能的显著改善相关（P<0.05）。相反，在治疗初治患者中停止 ART 或延迟开始治疗会导致与基线相比（13）呼气量显著下降（P<0.05）。与基线相比，从司他夫定或 ddI 转换为替诺福韦或阿巴卡韦的个体（13）呼气量显著增加（增加 170%；P<0.001），而在继续使用稳定方案的接受 ART 的个体或在改变蛋白酶抑制剂（PI）或非核苷逆转录酶抑制剂（NNRTI）成分的个体中，MeBT1 和 MeBT2 之间没有差异。
本研究数据表明，HIV 疾病中的肝线粒体功能是一个具有高再生能力的动态过程，并强调了 HIV 复制的发病相关性。我们的发现表明，现代 ART 本身不会对肝线粒体功能产生负面影响。
