Joly Véronique, Descamps Diane, Yeni Patrick
Hôpital Bichat-Claude Bernard 16 rue Henri Huchard 75877 Paris, France.
AIDS Rev. 2002 Jul-Sep;4(3):128-39.
Although not yet recommended, regimens combining both a non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitors (PI) can be used as first-line therapy, or as second-line or salvage therapy in patients who need to change antiretroviral treatment because of nucleoside reverse transcriptase inhibitors (NRTI) intolerance or virological failure with resistance to NRTI. Such combinations should not be used in patients infected with HIV-1 group O and HIV-2, due to the natural resistance to NNRTI of these subtypes. Dual NNRTI and PI combinations used as first-line therapy allow to spare NRTI, leaving a fully active class of drugs for later use, and delaying the risk of toxicity related to NRTI exposure, particularly mitochondrial toxicity. Several studies have shown that adding a NNRTI improves the efficacy of a second-line or salvage therapy based on a new combination of PI(s) and new or recycled NRTI(s). A possible explanation for the efficacy of NNRTI-containing regimens in NRTI-pretreated patients is that mutations conferring resistance to NRTI can increase the susceptibility of the viruses to the NNRTI. However, the decision to use a NNRTI in a salvage regimen needs to be weighed against the concern that subsequent failure will exhaust therapeutic options with any compound of this class, due the large degree of cross-resistance between the three available NNRTI. NNRTI and PIs are extensively metabolized in the liver through cytochrome P450, leading to pharmacokinetic interactions. The decrease in PIs plasma concentrations observed when they are combined with nevirapine or efavirenz is reduced when low doses of ritonavir, which strongly inhibits cytochrome P450, are associated with the combination of PI and NNRTI.
虽然尚未得到推荐，但将非核苷类逆转录酶抑制剂（NNRTI）与蛋白酶抑制剂（PI）联合使用的方案可作为一线治疗，或用于因对核苷类逆转录酶抑制剂（NRTI）不耐受或对NRTI耐药导致病毒学失败而需要更换抗逆转录病毒治疗的患者的二线或挽救治疗。由于HIV-1 O组和HIV-2亚型对NNRTI天然耐药，因此这类联合方案不应在感染这些亚型的患者中使用。将双重NNRTI与PI联合用作一线治疗可节省NRTI，为后续使用保留一类完全有效的药物，并降低与NRTI暴露相关的毒性风险，尤其是线粒体毒性。多项研究表明，添加一种NNRTI可提高基于新的PI组合以及新的或循环使用的NRTI的二线或挽救治疗的疗效。含NNRTI方案在接受过NRTI预处理的患者中疗效较好的一个可能解释是，赋予对NRTI耐药性的突变可增加病毒对NNRTI的敏感性。然而，在挽救治疗方案中使用NNRTI的决定需要权衡这样一个担忧，即由于三种可用的NNRTI之间存在很大程度的交叉耐药性，后续治疗失败将耗尽该类任何化合物的治疗选择。NNRTI和PI在肝脏中通过细胞色素P450进行广泛代谢，从而导致药代动力学相互作用。当低剂量的ritonavir（强烈抑制细胞色素P450）与PI和NNRTI联合使用时，PI与奈韦拉平或依非韦伦联合使用时观察到的PI血浆浓度降低情况会减少。
