Atazanavir: A new protease inhibitor to treat HIV infection
Atazanavir: A new protease inhibitor to treat HIV infection
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DOI：
10.1093/ajhp/61.13.1365
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发表时间：
2004-07-01
影响因子：
2.7
通讯作者：
Coleman, CI
中科院分区：
文献类型：
--
作者：
Musial, BL;Chojnacki, JK;Coleman, CI
目的.本文综述了阿扎那韦（atazanavir）的药理学、药代动力学、临床试验、药物相互作用和处方考虑。通过MEDLINE检索确定临床和药代动力学试验。此外，所有可用的文献引用和会议摘要均来自药物制造商。对从数据源中识别出的所有文章进行了评价，并将所有相关信息纳入本综述中。关于阿扎那韦治疗艾滋病毒感染的数据仅限于几项II期和III期试验，其中一项仍在进行中。阿扎那韦在降低HIV RNA水平、增加CD4+淋巴细胞计数和增加达到临床上不可检测的HIV RNA水平的患者百分比方面显示出与其他PI和非核苷逆转录酶抑制剂依法韦仑相当的疗效，在初治患者中作为唯一PI给药，在治疗经验丰富的患者中与沙奎那韦联合给药，在高度治疗经验丰富的患者中与利托那韦加强方案联合给药。接受阿扎那韦治疗的初治患者通常在密码子50上发生蛋白酶突变，这降低了HIV对阿扎那韦的易感性，但可能增加病毒对其他PI的易感性。当阿扎那韦给予预先存在PI相关突变的患者时，病毒对阿扎那韦的敏感性大大降低。血脂异常的发生，这一直是一个主要的关注与以往的PI，尚未被证明是麻烦的患者接受阿扎那韦。阿扎那韦可单独用作一线PI，在治疗经验丰富的患者中与沙奎那韦联合使用，或在治疗经验丰富的患者中与利托那韦加强方案联合使用，作为挽救治疗方案的一部分。
Purpose. The pharmacology, pharmacokinetics, and clinical trials of and drug interactions and formulary considerations associated with atazanavir, the newest protease inhibitor (PI) to treat human immunodeficiency virus (HIV) infection, are evaluated.Summary. Clinical and pharmacokinetic trials were identified through a MEDLINE search. In addition, all available literature citations and meeting abstracts were obtained from the drug's manufacturer. All articles identified from the data sources were evaluated, and all information deemed relevant was included in this review. Data on atazanavir for the treatment of HIV infection are limited to several phase II and III trials, one of which is still ongoing. Atazanavir has shown efficacy comparable with other Pis and the nonnucleoside reverse-transcriptase inhibitor efavirenz in reducing HIV RNA levels, increasing CD4+ lymphocyte counts, and increasing the percentage of patients achieving clinically undetectable HIV RNA levels when given as the sole PI in treatment-naive patients, in combination with saquinavir in treatment-experienced patients, and with ritonavir-boosting regimens in highly treatment-experienced patients. Treatment-naive patients receiving atazanavir commonly develop a protease enzyme mutation on codon 50, which decreases HIV's susceptibility to atazanavir but may increase the susceptibility of the virus to other Pis. When atazanavir is given to patients with preexisting PI-related mutations, the virus's susceptibility to atazanavir is greatly reduced. The occurrence of lipid abnormalities, which has been a major concern with previous Pis, has not been shown to be troublesome in patients receiving atazanavir.Conclusion. Atazanavir may be used alone as a first-line PI, with saquinavir in treatment-experienced patients, or in combination with a ritonavir-boosting regimen in highly treatment-experienced patients as part of a salvage regimen.