South Carolina College of Pharmacy, University of South Carolina Campus, Columbia, USA.
Ann Pharmacother. 2012 Apr;46(4):578-89. doi: 10.1345/aph.1Q616. Epub 2012 Apr 10.
To review the literature concerning the role of raltegravir in the treatment of HIV-1 in antiretroviral (ARV)-experienced and ARV-naïve patients.
A PubMed search was conducted for published data through March 2012 using the search terms raltegravir, MK-0518, and integrase strand transfer inhibitor. An additional search of International Pharmaceutical Abstracts for unpublished data, including data from the Infectious Diseases Society of America, the Conference on Retroviruses and Opportunistic Infections, the International AIDS Society, and the Interscience Conference on Antimicrobial Agents and Chemotherapy, was conducted using similar search terms.
In vitro and in vivo Phase 2, Phase 3, and postmarketing studies available in English, evaluating antiretroviral regimens that contain raltegravir for the treatment of HIV-1 infection in both ARV-naïve and ARV-experienced patients, were evaluated. Studies assessing raltegravir pharmacokinetics and pharmacodynamics were included for review.
The nucleoside-based regimen of raltegravir with tenofovir/emtricitabine provides an effective first-line treatment option. However, nucleoside-sparing regimens appear unfavorable in ARV-naïve subjects and should be reserved for patients with limited treatment options. Raltegravir used with optimized background therapy provides an alternative regimen for ARV-experienced patients. This review describes the available in vitro and in vivo data on raltegravir potency, defined as the ability to achieve undetectable viral load, and safety profile, as well as comparison to standard HIV-1 therapies.
Raltegravir has demonstrated potent antiretroviral activity against HIV-1 in both ARV-naïve and ARV-experienced subjects, with the benefits of a favorable adverse effect profile and minimal drug interactions. Raltegravir must be dosed twice daily, as once daily raltegravir displays decreased virologic efficacy compared to twice daily dosing. However, the ongoing development of new integrase strand transfer inhibitors may provide potent once daily regimens.
综述利托那韦在治疗抗逆转录病毒（ARV）经验和 ARV 初治的 HIV-1 中的作用的文献。
使用 raltegravir、MK-0518 和整合酶链转移抑制剂等检索词，对截至 2012 年 3 月发表的数据进行了 PubMed 检索。还使用了类似的检索词，对国际药学文摘中未发表的数据（包括传染病学会、逆转录病毒和机会性感染会议、国际艾滋病协会和抗菌化学疗法协会的科学会议）进行了检索。
评估了可用的英语体外和体内 2 期、3 期和上市后研究，评估了包含利托那韦的抗逆转录病毒方案治疗 ARV 初治和 ARV 经验丰富的 HIV-1 感染的疗效。包括评估利托那韦药代动力学和药效学的研究。
利托那韦与替诺福韦/恩曲他滨的核苷类方案提供了有效的一线治疗选择。然而，核苷类药物节省方案在 ARV 初治患者中似乎不利，应保留给治疗选择有限的患者。与优化背景治疗一起使用的利托那韦为 ARV 经验丰富的患者提供了另一种方案。本综述描述了利托那韦在体外和体内的活性、耐药性、药代动力学和药效学数据，以及与标准 HIV-1 治疗的比较。
利托那韦在 ARV 初治和 ARV 经验丰富的患者中均显示出对 HIV-1 的强大抗病毒活性，具有良好的不良反应谱和最小的药物相互作用的优势。利托那韦必须每日两次给药，因为与每日两次给药相比，每日一次利托那韦的病毒学疗效降低。然而，新的整合酶链转移抑制剂的不断发展可能会提供有效的每日一次方案。
