HIV Unit, Infectious Diseases Department, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
AIDS Rev. 2011 Jul-Sep;13(3):180-93.
Drug resistance is one of the key problems in the management of long-term HIV-1-infected patients. Due to cross-resistance patterns within classes, broad resistance to the three original antiretroviral classes can develop in some patients, mainly those with extensive antiretroviral treatment experience and multiple treatment failures. Triple-class-resistant HIV-1 infection has been associated with a higher risk of clinical progression and death. Additionally, it increases the probability of transmission of multidrug-resistant HIV-1 strains. Over the last years, the availability of new antiretroviral agents against novel targets (integrase inhibitors and CCR5 antagonists), and new drugs within old classes (nonnucleoside reverse transcriptase inhibitors and protease inhibitors) has opened a range of new therapeutic options for patients with multiclass drug-resistant HIV-1 infection and scarce therapeutic options with previous drugs. In randomized clinical trials, each of these new drugs has shown exceptional efficacy results, especially in patients who received other fully active drugs in the regimen. Indeed, in nonrandomized trials and observational studies, unprecedented rates of virologic suppression similar to those obtained in naive patients have been achieved when three of the currently available new drugs were combined, even in heavily experienced patients who had no viable salvage options with the previous classes. Thus, the goal of suppression and maintenance (plasma HIV-1 RNA < 50 copies/ml) is now also attainable in patients with multidrug-resistant HIV-1 infection. Treatment failure can still occur, however, and the management of patients with multidrug-resistant HIV-1 infection remains a challenge. Clinicians are encouraged to optimize use of the new drugs to obtain better control of HIV infection while avoiding emergence of new resistance-associated mutations. The aim of this article is to summarize current knowledge on the management of salvage therapy for patients with multidrug-resistant HIV-1 infection by analyzing the evidence extracted from clinical trials, and to review the information on the effectiveness of triple combinations of new drugs provided by non-comparative trials and observational studies.
耐药性是长期感染 HIV-1 的患者管理中的关键问题之一。由于类内的交叉耐药模式，一些患者（主要是那些具有广泛抗病毒治疗经验和多次治疗失败的患者）可能会广泛耐药于三种原始抗逆转录病毒药物。对三种抗逆转录病毒药物均耐药的 HIV-1 感染与更高的临床进展和死亡风险相关。此外，它增加了传播多种耐药性 HIV-1 株的可能性。在过去的几年中，针对新靶标的新型抗逆转录病毒药物（整合酶抑制剂和 CCR5 拮抗剂）以及旧类别的新药（非核苷类逆转录酶抑制剂和蛋白酶抑制剂）的出现，为多药耐药 HIV-1 感染且以前的药物治疗选择有限的患者提供了一系列新的治疗选择。在随机临床试验中，这些新药中的每一种都显示出了出色的疗效结果，尤其是在方案中使用了其他完全有效的药物的患者中。事实上，在非随机试验和观察性研究中，即使在没有以前类药物可行的挽救方案的经验丰富的患者中，当联合使用目前三种可用的新药时，也可以实现与初治患者相似的空前的病毒学抑制率。因此，抑制和维持（血浆 HIV-1 RNA<50 拷贝/ml）的目标现在也可以在多药耐药 HIV-1 感染的患者中实现。然而，治疗失败仍然可能发生，多药耐药 HIV-1 感染患者的管理仍然是一个挑战。鼓励临床医生优化新药物的使用，以更好地控制 HIV 感染，同时避免新的耐药相关突变的出现。本文的目的是通过分析临床试验中提取的证据，总结当前关于多药耐药 HIV-1 感染患者挽救治疗管理的知识，并综述非比较性试验和观察性研究提供的新药三联治疗的有效性信息。
