Polis M A, Sidorov I A, Yoder C, Jankelevich S, Metcalf J, Mueller B U, Dimitrov M A, Pizzo P, Yarchoan R, Dimitrov D S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Building 10, Room 11C103, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Lancet. 2001 Nov 24;358(9295):1760-5. doi: 10.1016/s0140-6736(01)06802-7.
Early assessment of antiretroviral drug efficacy is important for prevention of the emergence of drug-resistant virus and unnecessary exposure to ineffective drug regimens. Current US guidelines for changing therapy are based on measurements of plasma HIV-1 RNA concentrations 4 or 8 weeks after the start of treatment with cut-off points of 0.75 or 1.00 log, respectively. We investigated the possibility of assessing drug efficacy from measurements of plasma HIV-1 concentrations made during the first week on therapy.
The kinetics of virus decay in plasma during the first 12 weeks of treatment was analysed for 124 HIV-1-infected patients being treated for the first time with a protease inhibitor. Patients with a continuous decline of HIV-1 concentrations and in whom HIV-1 was either undetectable or declined by more than 1.5 log at 12 weeks were defined as good responders; the rest were poor responders.
The individual virus decay rate constants (k) at day 6 correlated significantly (r>0.66, p<0.0001) with changes in HIV-1 concentrations at 4, 8, and 12 weeks, and correctly predicted 84% of the responses with a cut-off value of k=0.21 per day (in log scale). Reduction in plasma HIV-1 of less than 0.72 log by day 6 after initiation of therapy predicted poor long-term responses in more than 99% of patients.
These results suggest that changes in HIV-1 concentration at day 6 after treatment initiation are major correlates of longer-term virological responses. They offer a very early measure of individual long-term responses, suggesting that treatment could be optimised after only a few days of therapy.
早期评估抗逆转录病毒药物疗效对于预防耐药病毒的出现以及避免不必要地暴露于无效治疗方案至关重要。美国目前的治疗调整指南基于治疗开始后4周或8周时血浆HIV-1 RNA浓度的测量结果，截断点分别为0.75或1.00 log。我们研究了从治疗第一周血浆HIV-1浓度测量结果评估药物疗效的可能性。
分析了124例首次接受蛋白酶抑制剂治疗的HIV-1感染患者治疗前12周血浆中病毒衰减的动力学。HIV-1浓度持续下降且在12周时HIV-1检测不到或下降超过1.5 log的患者被定义为良好反应者；其余为反应不佳者。
第6天的个体病毒衰减速率常数（k）与4周、8周和12周时HIV-1浓度的变化显著相关（r>0.66，p<0.0001），并且以k=0.21/天（对数尺度）的截断值正确预测了84%的反应。治疗开始后第6天血浆HIV-1下降小于0.72 log可预测超过99%的患者长期反应不佳。
这些结果表明，治疗开始后第6天HIV-1浓度的变化是长期病毒学反应的主要相关因素。它们提供了个体长期反应的非常早期的测量方法，表明仅在治疗几天后就可以优化治疗。
