Talwani R, Temesgen Z
Division of Infectious Diseases, Institute of Human Virology, University of Maryland, School of Medicine, Baltimore, Maryland, USA.
Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA.
Drugs Today (Barc). 2020 Feb;56(2):113-124. doi: 10.1358/dot.2020.56.2.3109966.
Doravirine is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) that was approved by the United States Food and Drug Administration (FDA) on August 30, 2018, for the treatment of HIV infection in adult patients. The product was also approved in the E.U. and Japan in November 2018 and January 2020, respectively. It is currently available as a single stand-alone tablet as well as part of a single-tablet regimen in a fixed-dose combination with tenofovir disoproxil and lamivudine. Similarly to other NNRTIs, doravirine exerts its antiviral effect through a noncompetitive inhibition of HIV-1 reverse transcriptase. It has a novel resistance pathway so that it retains in vitro activity against clinically relevant NNRTI viral mutations K103N, Y181C and G190A. In randomized clinical trials, doravirine was noninferior to efavirenz- and darunavir-based regimens, with fewer adverse events. Doravirine has a more favorable drug interaction profile compared with earlier NNRTIs as it neither inhibits nor induces the cytochrome P450 3A4 (CYP3A4) enzyme. Doravirine has been added to the category of Recommended Initial Regimens in Certain Clinical Situations in the United States Department of Health and Human Services Antiretroviral Guidelines for Adults and Adolescents.
多伟托是一种新型非核苷类逆转录酶抑制剂（NNRTI），于2018年8月30日获美国食品药品监督管理局（FDA）批准，用于治疗成年HIV感染患者。该产品分别于2018年11月和2020年1月在欧盟和日本获批。它目前有单一片剂剂型，也有与替诺福韦酯和拉米夫定组成的固定剂量复方单片治疗方案。与其他NNRTIs类似，多伟托通过非竞争性抑制HIV-1逆转录酶发挥抗病毒作用。它有一条新的耐药途径，因此对临床相关的NNRTI病毒突变K103N、Y181C和G190A在体外仍具有活性。在随机临床试验中，多伟托不劣于基于依非韦伦和达芦那韦的治疗方案，且不良事件较少。与早期的NNRTIs相比，多伟托具有更有利的药物相互作用情况，因为它既不抑制也不诱导细胞色素P450 3A4（CYP3A4）酶。多伟托已被纳入美国卫生与公众服务部《成人及青少年抗逆转录病毒治疗指南》中某些临床情况下的推荐初始治疗方案类别。
