Fätkenheuer G, Theisen A, Rockstroh J, Grabow T, Wicke C, Becker K, Wieland U, Pfister H, Reiser M, Hegener P, Franzen C, Schwenk A, Salzberger B
Department of Internal Medicine I, University of Cologne, Germany.
AIDS. 1997 Nov 15;11(14):F113-6. doi: 10.1097/00002030-199714000-00001.
To determine the rate of virological treatment failure with protease inhibitor therapy in unselected patients and to assess underlying risk factors.
Retrospective study in two German tertiary care treatment centres.
A total of 198 HIV-infected patients treated with protease inhibitors in 1996.
Levels of HIV RNA 1-6 months after start of treatment; definition of treatment failure of < 1 log10 reduction in plasma HIV RNA within 6 months after starting protease inhibitor therapy; multivariate analysis of risk factors for treatment failures.
A total of 226 treatment episodes with protease inhibitors were evaluable (saquinavir, 83; ritonavir, 47; indinavir, 96). The rate of virological treatment failure was 44% (saquinavir, 64%; ritonavir, 38%; indinavir, 30%). In a multivariate analysis, the following independent risk factors for virological failure were found: CD4 cell count, pretreatment with antiretroviral drugs (number), and protease inhibitor (compound). The relative risk reduction for each CD4 cell count increase was 0.997 (P = 0.012), 2.64 for pretreatment with one or two drugs versus no drug (P = 0.05), 2.97 for pretreatment with more than two drugs versus no drug (P = 0.05), and 4.62 for treatment with saquinavir versus indinavir (P = 0.001).
An unexpectedly high rate of virological treatment failure of protease inhibitor therapy was found in an unselected cohort of HIV-infected patients. Response to antiretroviral combination therapy in normal clinical practice may considerably differ from results of randomized clinical trials. Further studies are warranted to find optimal treatment strategies for both initial and salvage therapy.
确定在未经挑选的患者中使用蛋白酶抑制剂治疗的病毒学治疗失败率，并评估潜在风险因素。
在德国两个三级医疗治疗中心进行的回顾性研究。
1996年共有198例接受蛋白酶抑制剂治疗的HIV感染患者。
开始治疗后1 - 6个月的HIV RNA水平；蛋白酶抑制剂治疗开始后6个月内血浆HIV RNA降低不足1 log10定义为治疗失败；治疗失败风险因素的多变量分析。
共有226次蛋白酶抑制剂治疗疗程可进行评估（沙奎那韦83次；利托那韦47次；茚地那韦96次）。病毒学治疗失败率为44%（沙奎那韦64%；利托那韦38%；茚地那韦30%）。在多变量分析中，发现以下病毒学失败的独立风险因素：CD4细胞计数、抗逆转录病毒药物预处理（数量）和蛋白酶抑制剂（化合物）。CD4细胞计数每增加一次，相对风险降低0.997（P = 0.012），使用一种或两种药物预处理与未使用药物相比为2.64（P = 0.05），使用两种以上药物预处理与未使用药物相比为2.97（P = 0.05），使用沙奎那韦与茚地那韦治疗相比为4.62（P = 0.001）。
在未经挑选的HIV感染患者队列中发现蛋白酶抑制剂治疗的病毒学治疗失败率意外地高。正常临床实践中对抗逆转录病毒联合治疗的反应可能与随机临床试验结果有很大差异。有必要进行进一步研究以找到初始治疗和挽救治疗的最佳策略。
