换用含蛋白酶抑制剂的核苷类药物节省方案（洛匹那韦/利托那韦加依非韦伦）可增加肢体脂肪，但会提高血脂水平：一项前瞻性随机试验（艾滋病临床试验组5125s）的结果
Switching to a protease inhibitor-containing, nucleoside-sparing regimen (lopinavir/ritonavir plus efavirenz) increases limb fat but raises serum lipid levels: results of a prospective randomized trial (AIDS clinical trial group 5125s).
作者信息
Tebas Pablo, Zhang Jiameng, Yarasheski Kevin, Evans Scott, Fischl Margaret A, Shevitz Abby, Feinberg Judith, Collier Ann C, Shikuma Cecilia, Brizz Barbara, Sattler Fred
机构信息
Division of Infectious Diseases, University of Pennsylvania, Philadelphia, PA 19104, USA.
出版信息
J Acquir Immune Defic Syndr. 2007 Jun 1;45(2):193-200. doi: 10.1097/QAI.0b013e318042e204.
BACKGROUND
Subcutaneous limb fat loss continues to be one the most troubling side effects of long-term antiretroviral regimens. Nucleoside analogues and protease inhibitors (PIs) have been linked to the development of this complication.
METHODS
We evaluated the effects of nucleoside-sparing and PI-sparing regimens on fat distribution, bone mineral density, and metabolic parameters in 62 subjects, who were not selected for lipoatrophy, with advanced HIV (nadir CD4 count <or=200 cells/mm or HIV RNA level >or=80,000 copies/mL) and an undetectable HIV viral load. Participants were randomized to switch their initial successful antiretroviral regimen to open-label lopinavir/ritonavir (LPV/r) at a dose of 533/133 mg twice a day and efavirenz (EFV) at a dose of 600 mg/d (the nucleoside-sparing arm) versus EFV and 2 nucleoside analogues (the PI-sparing arm).
FINDINGS
At week 48, the median change in limb fat in the nucleoside-sparing arm was 562 g (6%, interquartile range [IQR]: -218-1186 g) versus a loss of -242 g (-4%, IQR: -539-452 g) in the nucleoside-containing PI-sparing arm (P = 0.086). At the time of last observation (median = 102 weeks, IQR: 73-152 weeks), a median gain of 782 g (10%, IQR: -380-1168 g) of limb fat was noted in the nonnucleoside arm (n = 22) versus a loss of 850 g (-15%, IQR: -1270 to -526 g) in the nucleoside-containing arm (n = 25; P = 0.002).
INTERPRETATION
The switch to a nucleoside-sparing combination antiretroviral regimen (LPV/r + EFV) was associated with significant improvement in limb fat. These results provide additional evidence that nucleoside analogues are important in the progressive limb fat loss that characterizes antiretroviral treatment and that switching medications can significantly improve this complication. This option has to be carefully balanced with the potential to increase serum lipid levels and the trend to increase virologic failure.
背景
皮下肢体脂肪减少仍然是长期抗逆转录病毒治疗方案最棘手的副作用之一。核苷类似物和蛋白酶抑制剂（PIs）与这种并发症的发生有关。
方法
我们评估了核苷类药物节省和蛋白酶抑制剂节省方案对62名未因脂肪萎缩入选的晚期HIV患者（最低点CD4细胞计数≤200个/立方毫米或HIV RNA水平≥80,000拷贝/毫升）且HIV病毒载量不可检测的脂肪分布、骨矿物质密度和代谢参数的影响。参与者被随机分配，将其最初成功的抗逆转录病毒治疗方案改为开放标签的洛匹那韦/利托那韦（LPV/r），剂量为533/133毫克，每日两次，以及依非韦伦（EFV），剂量为600毫克/天（核苷类药物节省组），与EFV和两种核苷类似物（蛋白酶抑制剂节省组）进行对比。
研究结果
在第48周时，核苷类药物节省组的肢体脂肪中位数变化为562克（6%，四分位间距[IQR]：-218至1186克），而含核苷类药物的蛋白酶抑制剂节省组减少了242克（-4%，IQR：-539至452克）（P = 0.086）。在最后一次观察时（中位数 = 102周，IQR：73至152周），非核苷组（n = 22）的肢体脂肪中位数增加了782克（10%，IQR：-380至1168克），而含核苷组（n = 25）减少了850克（-15%，IQR：-1270至-526克）（P = 0.002）。
解读
改用核苷类药物节省的联合抗逆转录病毒治疗方案（LPV/r + EFV）与肢体脂肪的显著改善相关。这些结果提供了更多证据，表明核苷类似物在抗逆转录病毒治疗所特有的进行性肢体脂肪减少中起重要作用，且换药可显著改善这种并发症。这种选择必须与血清脂质水平升高的可能性以及病毒学失败增加的趋势仔细权衡。
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