Stellbrink Hans-Jürgen
ICH and IPM Study Center Hamburg, Grindelallee 35, Hamburg, Germany. stellbrink@ ich-hamburg.de
Drug Des Devel Ther. 2009 Feb 6;2:281-8. doi: 10.2147/dddt.s3337.
Raltegravir has recently been licensed for the treatment of HIV-1 infection. Currently its use is limited to treatment-experienced patients and subjects with resistant virus. In addition to its activity in the setting of resistance and treatment failure, it appears to have great potential for first-line therapy and as a switch option for subjects with intolerance to other agents, as well. Overall tolerability in clinical trials was excellent, and the toxicity profile is non-overlapping with other agents, with no clear neuropsychiatric, gastrointestinal, or metabolic toxicity. Its metabolization occurs mainly via UGT1A1 rather than by the CYP450 system, resulting in a relatively unproblematic drug interaction profile. The independence of the compound from "boosting" of drug levels with ritonavir is an attractive feature for many patients suffering from ritonavir-associated side effects. However, it has to be dosed twice daily.The unique effect of raltegravir on the establishment of viral latency makes it a logical component of treatment attempts aiming at reducing and controlling this viral sanctuary.This review summarizes the clinical view on the role of this novel compound in HIV therapy.
拉替拉韦最近已被批准用于治疗HIV-1感染。目前，其应用仅限于有治疗经验的患者和感染耐药病毒的受试者。除了在耐药和治疗失败情况下具有活性外，它在一线治疗以及作为对其他药物不耐受受试者的换药选择方面似乎也有很大潜力。临床试验中的总体耐受性良好，毒性特征与其他药物不重叠，没有明显的神经精神、胃肠道或代谢毒性。其代谢主要通过UGT1A1而非CYP450系统进行，导致药物相互作用情况相对简单。该化合物不依赖利托那韦提高药物水平，这对许多患有利托那韦相关副作用的患者来说是一个有吸引力的特性。然而，它必须每日给药两次。拉替拉韦对建立病毒潜伏的独特作用使其成为旨在减少和控制这种病毒庇护所的治疗尝试的合理组成部分。本综述总结了关于这种新型化合物在HIV治疗中作用的临床观点。
