Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development

作者：Elizabeth A. Martin, Ming‐Tain Lai, Winnie Ngo, Meizhen Feng, Donald J. Graham, Daria J. Hazuda, Sushma Kumar, Carey Hwang, Peter Sklar, Ernest Asante‐Appiah · 发表于：JAIDS Journal of Acquired Immune Deficiency Syndromes · 年份：2020 · DOI：10.1097/qai.0000000000002496 · 被引用次数：49 · 研究领域：HIV/AIDS drug development and treatment、Biochemical and Molecular Research、HIV Research and Treatment

BACKGROUND: Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) approved for the treatment of HIV-1 infection in patients with no known DOR resistance-associated mutations. DOR was rationally designed to address limitations associated with other approved NNRTIs, particularly resistance from common NNRTI resistance-associated mutants containing K103N, Y181C, or G190A reverse transcriptase substitutions. SETTING: Data to date from both in vitro studies and clinical trials have been compiled to summarize the resistance profile of DOR. METHODS: We analyzed data from in vitro studies and phase 2 and 3 trials to assess the emergence of resistance-associated mutations and their impact on efficacy among participants treated with DOR. RESULTS: DOR exhibited a distinct resistance profile compared with efavirenz and rilpivirine in vitro and in vivo; mutant viruses that were resistant to DOR showed limited cross-resistance to efavirenz and rilpivirine. In clinical trials, the development of DOR resistance-associated substitutions in reverse transcriptase was uncommon. CONCLUSION: Overall, minimal cross-resistance across NNRTIs was observed for DOR and limited development of DOR-related resistance. These data should assist clinicians in further understanding the resistance profile of DOR, so appropriate treatment decisions can be made for their patients.