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马拉维若用于HIV感染的一线治疗。风险太大。

Maraviroc first-line therapy for HIV infection. Too risky.

出版信息

Prescrire Int. 2010 Nov;19(110):252-4.

Abstract

First-line treatment for HIV infection currently comprises a combination of antiretroviral drugs, including a non-nucleoside reverse transcriptase inhibitor such as efavirenz, or one or two protease inhibitors.The choice is based on the results of initial clinical trials of antiretroviral drugs with morbidity and mortality endpoints, and, since the 1990s, on trials with surrogate markers (viral load and the CD4+ T lymphocyte count). Maraviroc is the only CCR5 antagonist currently on the market. Drugs belonging to this class are designed to prevent HIV entry into CD4 T lymphocytes. Maraviroc is reserved for patients with multiple treatment failure, but has also been proposed for first-line treatment. Clinical evaluation of maraviroc in first-line treatment is limited to a single comparative trial designed to show the virological and immunological "non-inferiority" of the maraviroc + zidovudine + lamivudine combination versus efavirenz + zidovudine + lamivudine, after 96 weeks of treatment, in 721 patients with CCR5-tropic HIV strains. A more sensitive version of the test used to determine CCR5 tropism became available during the trial, leading to the exclusion of 107 patients who were infected by strains capable of using other coreceptors. This trial fails to answer important questions regarding the adverse effects of maraviroc, such as hepatotoxicity, infections, cancer, and cardiovascular disorders. Tests used to identify exclusively CCR5-tropic HIV strains are difficult to implement and their results are unreliable. This means that some patients in whom maraviroc will not be effective may receive this drug, and will thus be at risk of developing viral resistance to other drugs in their antiretroviral regimen. In practice, first-line use of maraviroc is imprudent, as it depends on a test of uncertain reliability. Furthermore, there is no evidence to suggest that maraviroc combination therapy has a better risk-benefit balance than regimens with well-documented and long established efficacy.

摘要

目前,HIV感染的一线治疗方案是多种抗逆转录病毒药物的联合使用,其中包括一种非核苷类逆转录酶抑制剂,如依非韦伦,或一两种蛋白酶抑制剂。治疗方案的选择基于以发病率和死亡率为终点的抗逆转录病毒药物的初始临床试验结果,自20世纪90年代以来,还基于使用替代指标(病毒载量和CD4+T淋巴细胞计数)的试验结果。马拉维罗是目前市场上唯一的CCR5拮抗剂。这类药物旨在防止HIV进入CD4 T淋巴细胞。马拉维罗适用于多次治疗失败的患者,但也有人提议将其用于一线治疗。马拉维罗一线治疗的临床评估仅限于一项单一的对照试验,该试验旨在显示在721例感染CCR5嗜性HIV毒株的患者中,经过96周治疗后,马拉维罗+齐多夫定+拉米夫定联合用药与依非韦伦+齐多夫定+拉米夫定相比,在病毒学和免疫学上的“非劣效性”。在试验期间,出现了一种用于确定CCR5嗜性的更敏感的检测方法,导致107例感染了能够使用其他共受体的毒株的患者被排除。该试验未能回答有关马拉维罗不良反应的重要问题,如肝毒性、感染、癌症和心血管疾病。用于专门识别CCR5嗜性HIV毒株的检测方法难以实施,其结果也不可靠。这意味着一些使用马拉维罗无效的患者可能会使用这种药物,从而有在其抗逆转录病毒治疗方案中对其他药物产生病毒耐药性的风险。在实际应用中,一线使用马拉维罗是不谨慎的,因为这取决于一项可靠性不确定的检测。此外,没有证据表明马拉维罗联合治疗的风险效益比优于已充分证明且长期有效的治疗方案。

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