Safety and efficacy of switching to alternative nucleoside analogues following symptomatic hyperlactatemia and lactic acidosis
Safety and efficacy of switching to alternative nucleoside analogues following symptomatic hyperlactatemia and lactic acidosis
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DOI：
10.1097/00002030-200311210-00012
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发表时间：
2003-11-21
期刊：
影响因子：
3.8
通讯作者：
Mathews, WC
中科院分区：
文献类型：
--
作者：
Lonergan, JT;Barber, RE;Mathews, WC
目的：评价核苷类逆转录酶抑制剂(NRT1)诱导的症状性高乳酸血症或乳酸中毒患者使用含NRT1的替代方案进行复查的安全性和有效性。有症状的高乳酸血症病例是接受NRT1治疗的HIV感染的成年人，他们的症状与高乳酸血症和两种乳酸盐相适应，是正常上限的两倍。乳酸酸中毒的定义为乳酸+5 mmoL/L+碳酸氢盐+20 mmoL/L。用其他被认为具有同等抗病毒效力但线粒体毒性较小的nrt1替代先前方案中可疑的nrt1。结果：10例确诊为症状性高乳酸血症和2例乳酸酸中毒患者后来重新开始使用包括新的nrt1在内的抗逆转录病毒药物。确诊为症状性高乳酸血症或乳酸血症的患者接受的NRT1包括司他夫定和拉米夫定(n=6)、司他夫定和地丹核苷(n=4)、司他夫定和阿巴卡韦(n=2)。血乳酸峰值中位数为5.4(4.7~19.1)mm o l/L，5例再用阿巴卡韦和拉米夫定，5例用齐多夫定、阿巴卡韦和拉米夫定，2例用齐多夫定和拉米夫定。在超过22年的累积再暴露于含NRT1治疗的12名患者中，1名患者再次出现症状性高乳酸血症，复发率为45.5例/1000人年。所有患者都保持了病毒学控制。结论：这一数据支持这样的策略，即在毒性与司他夫定和/或地丹诺辛相关的症状性高乳酸血症或乳酸酸中毒病例中，重新引入NRT1是安全有效的，它们是较弱的线粒体抑制物。(C)2003年，里平科特·威廉姆斯·威尔金斯。
Objective: To evaluate the safety and efficacy of rechallenging patients who have recovered from nucleoside reverse transcriptase inhibitor (NRT1)-induced symptomatic hyperlactatemia or lactic acidosis with alternative NRT1-containing regimens.Methods: Data in this case series was collected from patients followed at the UCSD Owen Clinic from July 1998 through September 2002. Cases of symptomatic hyperlactatemia were HIV-infected adults receiving NRT1 who had symptoms compatible with hyperlactatemia and two lactates > 2 times the upper normal limit. Lactic acidosis was defined as lactate > 5 mmol/l with bicarbonate < 20 mmol/l. The suspected offending NRT1 in the prior regimen were replaced with other NRT1 thought to have equivalent antiviral potency but less mitochondrial toxicity.Results: Ten patients diagnosed with symptomatic hyperlactatemia and two with lactic acidosis were later restarted on antiretrovirals that included new NRT1. The NRT1 that patients were receiving when symptomatic hyperlactatemia or lactic acidosis was diagnosed included stavudine and lamivudine (n = 6), stavudine and didanosine (n = 4), and stavudine and abacavir (n = 2). The median (range) peak lactate was 5.4 (4.7-19.1) mmol/l. Five patients were rechallenged with abacavir and lamivudine, five with zidovudine, abacavir and lamivudine, and two with zidovudine and lamivudine. Among the 12 patients contributing over 22 years of cumulative reexposure to NRT1-containing therapy, one developed symptomatic hyperlactatemia again yielding a recurrence rate of 45.5 cases/1000 patient-years. Virologic control was maintained in all patients.Conclusions: This data supports the strategy that in cases of symptomatic hyperlactatemia or lactic acidosis in which the toxicity is associated with stavudine, didanosine or both, it is safe and efficacious to reintroduce NRT1 that are less potent inhibitors of mitochondria. (C) 2003 Lippincott Williams Wilkins.