Lluita contra la SIDA Foundation, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
AIDS Rev. 2009 Oct-Dec;11(4):215-22.
Lopinavir/ritonavir has been the recommended boosted protease inhibitor for treatment-naive individuals in all guidelines since its approval in the year 2000. More recently, the rest of ritonavir-boosted protease inhibitors (namely lopinavir once-daily, fosamprenavir, saquinavir, atazanavir, and darunavir) have demonstrated non-inferior antiviral efficacy at 48 weeks than lopinavir twice-daily. Overall, all ritonavir-boosted protease inhibitors display a high genetic and pharmacological barrier to resistance development and protect the rest of the drugs on board in the regimen, achieving similar CD4 count gains among them. During the last year, studies conducted with atazanavir and darunavir have demonstrated superior virologic efficacy against lopinavir at 96 weeks in their pivotal trials. These two protease inhibitors provide significant improvements in triglycerides and gastrointestinal toxicity, together with simpler once-daily formulations, compared to lopinavir. In the case of atazanavir, this is mainly driven by a lower rate of discontinuations due to drug-related side effects, as pure antiviral efficacy is essentially similar to lopinavir. Furthermore, the gastrointestinal intolerance of lopinavir is actually compensated by an increased risk of hyperbilirubinemia and jaundice with atazanavir, but this is more a cosmetic problem and rarely a cause of drug withdrawal. Darunavir has been licensed to be taken once-daily in treatment-naive patients, and shows significantly better lipid and gastrointestinal tolerance than lopinavir. Robust sensitivity analysis with darunavir prove superior antiviral efficacy than lopinavir at 96 weeks also when non-virologic failures (toxicity and discontinuations) are censored, or when only patients receiving lopinavir twice-daily are included in the estimation. Moreover, darunavir has shown superior antiviral efficacy than lopinavir, particularly in three situations of particular clinical concern: high baseline viral load, low baseline CD4 counts, and suboptimal drug adherence. Over the last years, the treatment landscape with ritonavir-boosted protease inhibitors as initial HIV therapy has accomplished significant advances, with improved degrees of efficacy, tolerability, and convenience, that should be used to guide treatment choice in first-line antiretroviral therapy.
洛匹那韦利托那韦自 2000 年获得批准以来，一直是所有指南中推荐用于初治患者的首选增效蛋白酶抑制剂。最近，其他利托那韦增强型蛋白酶抑制剂（即洛匹那韦每日一次、福沙那韦、沙奎那韦、阿扎那韦和达芦那韦）在 48 周时显示出与洛匹那韦每日两次非劣效的抗病毒疗效。总的来说，所有利托那韦增强型蛋白酶抑制剂对耐药性的发展都具有较高的遗传和药理学屏障，并保护方案中的其他药物，在它们之间实现类似的 CD4 计数增加。在过去的一年中，阿扎那韦和达芦那韦的研究在其关键试验中显示，在 96 周时，与洛匹那韦相比，它们具有更好的病毒学疗效。与洛匹那韦相比，这两种蛋白酶抑制剂在甘油三酯和胃肠道毒性方面有显著改善，并且采用了更简单的每日一次的制剂。对于阿扎那韦，这主要是由于因药物相关副作用而停药的发生率较低，因为纯抗病毒疗效与洛匹那韦基本相似。此外，洛匹那韦的胃肠道不耐受实际上被阿扎那韦引起的高胆红素血症和黄疸的风险所抵消，但这更多是一个美容问题，很少导致停药。达芦那韦已被批准用于初治患者，每日一次服用，与洛匹那韦相比，具有明显更好的血脂和胃肠道耐受性。用达芦那韦进行的稳健敏感性分析证明，在 96 周时，即使将非病毒学失败（毒性和停药）进行 censoring，或者仅将接受洛匹那韦每日两次的患者纳入估计中，也具有优于洛匹那韦的抗病毒疗效。此外，达芦那韦在三种特别值得关注的临床情况下，表现出优于洛匹那韦的抗病毒疗效，特别是在基线病毒载量高、基线 CD4 计数低和药物依从性差的情况下。在过去的几年中，利托那韦增强型蛋白酶抑制剂作为初始 HIV 治疗的治疗领域取得了显著进展，提高了疗效、耐受性和便利性，这些都应该用于指导一线抗逆转录病毒治疗中的治疗选择。
