Department for Infectious and Tropical Diseases, University of Brescia, Brescia, Italy.
Drugs. 2012 Jun 18;72(9):1161-73. doi: 10.2165/11631070-000000000-00000.
Atazanavir (Reyataz®) is a protease inhibitor (PI) for the treatment of HIV infection. Several trials have demonstrated the good efficacy and toxicity profile of atazanavir boosted by ritonavir (atazanavir/r). However, several toxicity events and pharmacokinetic issues due to drug-to-drug interactions (partly related to ritonavir) may complicate atazanavir/r therapy. This is why regimens with unboosted atazanavir have been experimented with and are used in clinical practice. The aim of this article is to identify the clinical settings in which unboosted atazanavir may be a safe and effective option for the long-term control of HIV replication. Despite the fact that a favourable lipid profile and good gastrointestinal tolerability have been reported in comparative trials, unboosted atazanavir should not be considered an optimal choice for treatment-naive patients. In fact, boosting with ritonavir produces higher atazanavir plasma levels, which are beneficial in terms of efficacy, especially in untreated patients with high plasma HIV RNA. Clinical data indicate that, in patients with sustained undetectable HIV RNA and without previous virological failure or HIV drug resistance-associated mutations, a switch to unboosted atazanavir-based regimens is a feasible option to control and prevent toxicity events, especially in patients who cannot tolerate ritonavir and in those with severe hyperbilirubinaemia on atazanavir/r. Moreover, while unboosted atazanavir must not be used in pregnant women, it is a recommended option in special populations, such as patients with moderate liver insufficiency. Lastly, unboosted atazanavir in combination with raltegravir may allow the construction of a well tolerated and effective regimen without nucleoside reverse transcriptase inhibitors in patients for whom these drugs are contraindicated. In conclusion, there is a good rationale, significant clinical interest and accumulating clinical experience with unboosted atazanavir-based regimens, although this formulation should be used only in specific situations and as a maintenance strategy. Moreover, therapeutic drug monitoring could be useful in specific circumstances (such as in patients with liver impairment or in case of potential drug-drug interactions).
阿扎那韦（Reyataz®）是一种用于治疗 HIV 感染的蛋白酶抑制剂（PI）。多项试验已经证明，阿扎那韦与利托那韦（atazanavir/r）联合使用具有良好的疗效和毒性特征。然而，由于药物相互作用（部分与利托那韦有关）引起的一些毒性事件和药代动力学问题可能会使阿扎那韦/r 治疗复杂化。这就是为什么人们尝试使用未增强的阿扎那韦方案，并在临床实践中使用这些方案。本文的目的是确定在哪些临床情况下，未增强的阿扎那韦可能是长期控制 HIV 复制的安全有效的选择。尽管在比较试验中已经报道了有利的血脂谱和良好的胃肠道耐受性，但未增强的阿扎那韦不应被视为治疗初治患者的最佳选择。事实上，与利托那韦联合使用可提高阿扎那韦的血浆水平，这在疗效方面是有益的，特别是在未经治疗的、高血浆 HIV RNA 的患者中。临床数据表明，对于 HIV RNA 持续不可检测且无先前病毒学失败或 HIV 耐药相关突变的患者，转换为基于未增强的阿扎那韦的方案是控制和预防毒性事件的可行选择，特别是在不能耐受利托那韦的患者和阿扎那韦/r 治疗时胆红素升高严重的患者中。此外，虽然不能在孕妇中使用未增强的阿扎那韦，但在某些特殊人群中，如中度肝功能不全的患者，它是一种推荐的选择。最后，未增强的阿扎那韦与拉替拉韦联合使用可在不能使用这些药物的患者中构建一种耐受良好且有效的方案，而无需使用核苷逆转录酶抑制剂。总之，未增强的阿扎那韦方案具有良好的理论基础、重要的临床意义和不断积累的临床经验，但这种制剂仅应在特定情况下使用，并且作为维持治疗策略。此外，在特定情况下（如肝功能受损或潜在药物相互作用的情况下），治疗药物监测可能会很有用。
