Ramkumar Kavya, Neamati Nouri
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, USA.
Core Evid. 2010 Jun 15;4:131-47. doi: 10.2147/ce.s6004.
The antiretroviral treatment paradigm for human immunodeficiency virus-1 (HIV-1) infection has undergone a significant change with the addition of a new class of therapeutic agents targeting HIV-1 integrase (IN). IN inhibitors prevent the integration of viral DNA into the human genome and terminate the viral life cycle. As the first member of this new class of anti-HIV drugs, raltegravir has shown promising results in the clinic.
To review the emerging evidence for the use of the IN inhibitor raltegravir in the treatment of HIV-1 infection.
Strong evidence shows that raltegravir is effective in reducing the viral load to less than 50 copies/mL and increasing CD4 cell count in treatment-experienced patients with triple-drug class-resistant HIV-1 infection. Substantial evidence also indicates that while raltegravir is able to achieve treatment response in patients with drug-resistant HIV-1, it is susceptible to development of resistance. Raltegravir should be used with at least one other active drug. In addition to its use in salvage therapy upon failure of first-line antiretroviral treatment, a raltegravir-based treatment regimen may also be effective as initial therapy. Substantial evidence also shows that raltegravir-based treatment regimen is well tolerated with minimal clinically severe adverse events and toxicities. Modeling studies suggest a cost-effectiveness of US$21,339 per quality-adjusted life year gained with raltegravir use, though further direct evidence on quality of life and cost-effectiveness is needed.
Raltegravir shows significant and sustained virologic and immunologic response in combination with other antiretrovirals in treatment-experienced HIV-1 infected patients who show evidence of viral replication or multidrug-resistant HIV-1 strains, without any significant tolerability issues.
随着一类针对人类免疫缺陷病毒1型（HIV-1）整合酶（IN）的新型治疗药物的加入，HIV-1感染的抗逆转录病毒治疗模式发生了重大变化。IN抑制剂可阻止病毒DNA整合到人类基因组中，从而终止病毒生命周期。作为这类新型抗HIV药物的首个成员，raltegravir（雷特格韦）在临床上已显示出令人期待的结果。
综述关于IN抑制剂raltegravir用于治疗HIV-1感染的新证据。
有力证据表明，raltegravir在治疗经历过三种药物类别耐药的HIV-1感染的患者中，能有效将病毒载量降至50拷贝/毫升以下并增加CD4细胞计数。大量证据还表明，虽然raltegravir能够使耐药HIV-1患者获得治疗反应，但它易产生耐药性。Raltegravir应与至少一种其他活性药物联合使用。除了在一线抗逆转录病毒治疗失败后用于挽救治疗外，基于raltegravir的治疗方案作为初始治疗也可能有效。大量证据还表明，基于raltegravir的治疗方案耐受性良好，临床严重不良事件和毒性最小。模型研究表明，使用raltegravir每获得一个质量调整生命年的成本效益为21,339美元，不过还需要关于生活质量和成本效益的进一步直接证据。
Raltegravir与其他抗逆转录病毒药物联合使用时，在有病毒复制证据或感染多药耐药HIV-1毒株的有治疗经验的HIV-1感染患者中显示出显著且持续的病毒学和免疫学反应，且无任何明显的耐受性问题。
