Pierre et Marie Curie University PARIS VI, Hospital Pitié-Salpêtrière, Department of Infectious Diseases, Paris, France.
Expert Opin Investig Drugs. 2012 Apr;21(4):523-30. doi: 10.1517/13543784.2012.661713. Epub 2012 Mar 2.
Development of new antiretroviral drugs which are highly potent, tolerable over the long term and with a high genetic barrier to resistance is essential for the treatment of a chronic viral disease that requires life-long therapy with near-perfect medication adherence. Integrase inhibitors (INI) are a new class of antiretroviral drugs that block the action of HIV integrase, which catalyses several key steps in the virus life cycle which are essential for insertion of the viral genome into the DNA of host cell.
Dolutegravir (DTG), a second-generation INI currently in the late stage of clinical development, is an effective orally available drug with a long half-life that does not need to be pharmacologically enhanced, is effective as a once daily drug in the absence of INI resistance mutations and twice daily in presence of INI resistance mutations.
DTG, as other drugs in the INI class, appears safe and well tolerated. Results from ongoing large Phase III studies will bring more generalizable and robust information on the long-term effects of DTG.
开发高效、长期耐受且具有高遗传耐药屏障的新型抗逆转录病毒药物对于治疗需要终身治疗且需要近乎完美的药物依从性的慢性病毒病至关重要。整合酶抑制剂（INI）是一类新型的抗逆转录病毒药物，可阻断 HIV 整合酶的作用，该酶催化病毒生命周期中的几个关键步骤，对于病毒基因组插入宿主细胞 DNA 至关重要。
目前处于临床开发后期的第二代 INI 药物多替拉韦（DTG）是一种有效的口服药物，半衰期长，无需药物增强，在没有 INI 耐药突变的情况下，每天一次有效，有 INI 耐药突变时，每天两次有效。
DTG 与 INI 类的其他药物一样，似乎安全且耐受良好。正在进行的大型 III 期研究的结果将提供关于 DTG 的长期效果的更具普遍性和更可靠的信息。
