Pandey Krishan K
1100 South Grand Boulevard, E. A. Doisy Research Center, Institute for Molecular Virology Saint Louis University Health Sciences Center, Saint Louis, MO 63104 USA.
Clin Med Rev Ther. 2011 Dec 20;2012(4):13-30. doi: 10.4137/CMRT.S5022.
The hunt for a compound which inhibits the HIV-1 integrase had been painstakingly difficult. Integrase is essential for viral replication as it mediates the integration of the viral DNA genome into the host DNA resulting in the establishment of the permanent provirus. Persistent efforts have resulted in the discovery of Raltegravir (Isentress, MK-0518), the first integrase inhibitor approved by US Food and Drug Administration for the treatment in HIV-1 infected patients. Numerous clinical studies with raltegravir have found it to be safe and effective in treatment naïve as well as treatment experienced patients. Adverse events associated with raltegravir based therapy are milder compared to previously available regimens. Raltegravir is metabolized primarily via glucuronidation mediated by uridine diphosphate glucuronosyltransferase and has a favorable pharmacokinetics independent of age, gender, race, food, and drug-drug interactions. Within a short period of time of its introduction, raltegravir has been included as one of DHHS recommended preferred regimen for the treatment of HIV-1 infection in treatment naïve patients.
寻找一种能够抑制HIV-1整合酶的化合物一直极为困难。整合酶对于病毒复制至关重要，因为它介导病毒DNA基因组整合到宿主DNA中，从而形成永久性的前病毒。经过不懈努力，发现了拉替拉韦（艾生特，MK-0518），这是美国食品药品监督管理局批准的首个用于治疗HIV-1感染患者的整合酶抑制剂。多项关于拉替拉韦的临床研究发现，它在初治患者和经治患者中均安全有效。与基于拉替拉韦的治疗相关的不良事件比以前的治疗方案更为轻微。拉替拉韦主要通过尿苷二磷酸葡萄糖醛酸基转移酶介导的葡萄糖醛酸化进行代谢，并且具有良好的药代动力学，不受年龄、性别、种族、食物和药物相互作用的影响。在引入后的短时间内，拉替拉韦已被纳入美国卫生与公众服务部推荐的初治HIV-1感染患者首选治疗方案之一。
