Deeks S G, Smith M, Holodniy M, Kahn J O
University of California, San Francisco, USA.
JAMA. 1997 Jan 8;277(2):145-53.
The clinical care of people infected with human immunodeficiency virus (HIV) has been substantially affected by the introduction of HIV-specific protease inhibitors (PIs). The 4 PIs available are saquinavir mesylate, ritonavir, indinavir sulfate, and nelfinavir mesylate. Comparison studies have not been reported; therefore, an assessment of the available data to aid clinicians and patients in choosing appropriate treatment will be presented.
A systematic review of peer-reviewed publications, abstracts from national and international conferences, and product registration information through September 1996.
Criteria used to select studies include their relevance to PIs, having been published in the English language, and pertinence for clinicians. Data quality and validity included the venue of the publication and relevance to clinical care.
Oral adminstration of ritonavir, indinavir, or nelfinavir generates sustainable drug serum levels to effectively inhibit the protease enzyme; however, saquinavir may not generate sustained levels necessary to inhibit the protease enzyme. Patients treated with ritonavir, indinavir, or nelfinavir experience similar reductions in viral load and increases in CD4+ lymphocytes; smaller effects occur among those treated with saquinavir. Two randomized placebo-controlled studies conducted among patients with severe immune system suppression and substantial zidovudine treatment experience demonstrated reduced HIV disease progression and reduced mortality with PI treatment. Genotypic resistance to PIs occurs; the clinical relevance of resistance is unclear. The costs of these agents including required monitoring impose new and substantial costs.
The PIs have emerged as critical drugs for people with HIV infection. Optimal use involves combination with reverse transcriptase inhibitors. Resistance develops to each agent, and cross-resistance is likely. These agents must be used at full doses with attention to ensuring patient compliance. The expense of these agents may be offset by forestalling disease progression and death and returning people to productive life. Selecting the initial PI must be individualized, and factors to consider include proven activity, possible toxicities, dosing regimens, drug interactions, and costs.
感染人类免疫缺陷病毒（HIV）者的临床护理已受到HIV特异性蛋白酶抑制剂（PIs）引入的显著影响。现有的4种蛋白酶抑制剂分别是甲磺酸沙奎那韦、利托那韦、硫酸茚地那韦和甲磺酸奈非那韦。尚未见比较研究报告；因此，本文将对现有数据进行评估，以帮助临床医生和患者选择合适的治疗方法。
对截至1996年9月的同行评审出版物、国内和国际会议摘要以及产品注册信息进行系统综述。
用于选择研究的标准包括其与蛋白酶抑制剂的相关性、以英文发表以及对临床医生的相关性。数据质量和有效性包括出版物的发表地点以及与临床护理的相关性。
口服利托那韦、茚地那韦或奈非那韦可产生可持续的药物血清水平，以有效抑制蛋白酶；然而，沙奎那韦可能无法产生抑制蛋白酶所需的持续水平。接受利托那韦、茚地那韦或奈非那韦治疗的患者病毒载量有类似程度的降低，CD4 +淋巴细胞数量增加；接受沙奎那韦治疗的患者变化较小。在免疫系统严重抑制且有大量齐多夫定治疗经验的患者中进行的两项随机安慰剂对照研究表明，蛋白酶抑制剂治疗可降低HIV疾病进展并降低死亡率。对蛋白酶抑制剂会出现基因型耐药；耐药的临床相关性尚不清楚。这些药物的成本包括所需的监测，带来了新的巨大成本。
蛋白酶抑制剂已成为HIV感染者的关键药物。最佳用法是与逆转录酶抑制剂联合使用。每种药物都会产生耐药，且可能存在交叉耐药。这些药物必须足量使用，并注意确保患者依从性。这些药物的费用可能因预防疾病进展和死亡以及使患者恢复有生产能力的生活而得到抵消。选择初始蛋白酶抑制剂必须个体化，需考虑的因素包括已证实的活性、可能的毒性、给药方案、药物相互作用以及成本。
