Tsai Hung-Chin, Chen I-Tzu, Chang Hui-Min, Lee Susan Shin-Jung, Chen Yao-Shen
Division of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Infect Drug Resist. 2022 Jul 20;15:3857-3869. doi: 10.2147/IDR.S361012. eCollection 2022.
This study aimed to investigate the prevalence of resistance to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based single-tablet regimen (STR) in Taiwanese patients and clarify the clinical implications of using doravirine in patients who fail NNRTI treatment.
Taiwanese patients infected with HIV-1 who failed NNRTI-based STR treatment were enrolled in this retrospective cohort study from 2015 to 2020. Mutations associated with drug resistance were identified using the 2019 International Antiviral Society-USA list of drug-resistant mutations in HIV, and drug susceptibility was assessed according to the Stanford HIV Drug Resistance Database version 9. Median values of continuous variables were compared between two groups using the Mann-Whitney -test, and categorical variables were compared using the chi-square test or Fisher's exact test.
A total of 107 patients were included, of whom 29 were treatment failure to the initial STRs, and 78 failed treatment after switching to an STR. Seventy-four patients failed treatment with TDF/FTC/EFV (Atripla), 30 with TDF/FTC/RPV (Complera) and 3 with TAF/FTC/RPV (Odefsey). The prevalence rates of resistance to nucleoside reverse transcriptase inhibitors (NRTIs), NNRTIs, protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) were 76%, 86%, 3% and 2%, respectively. Among the 29 patients failure to the initial STRs, 62% developed doravirine resistance, compared to 64% of the 78 the patients who failed treatment after switching to an STR. There were no significant differences in the prevalence of specific NNRTI or doravirine resistance-associated mutations between these two groups. The patients with K65R mutations were more likely to have NNRTI resistance (p = 0.037) and doravirine resistance (p < 0.001).
Our findings showed a high rate of doravirine cross-resistance in patients with NNRTI-based STR treatment failure. Doravirine should be used cautiously as a salvage regimen in patients who fail NNRTI treatment.
本研究旨在调查台湾患者中对基于非核苷类逆转录酶抑制剂（NNRTI）的单片复方制剂（STR）耐药的发生率，并阐明在接受NNRTI治疗失败的患者中使用多拉韦林的临床意义。
本回顾性队列研究纳入了2015年至2020年期间接受基于NNRTI的STR治疗失败的台湾HIV-1感染患者。使用2019年美国国际抗病毒协会的HIV耐药突变列表鉴定与耐药相关的突变，并根据斯坦福HIV耐药数据库第9版评估药物敏感性。连续变量的中位数在两组之间使用Mann-Whitney检验进行比较，分类变量使用卡方检验或Fisher精确检验进行比较。
共纳入107例患者，其中29例对初始STR治疗失败，78例在换用STR后治疗失败。74例患者使用替诺福韦酯/恩曲他滨/依非韦伦（Atripla）治疗失败，30例使用替诺福韦酯/恩曲他滨/利匹韦林（Complera）治疗失败，3例使用丙酚替诺福韦/恩曲他滨/利匹韦林（Odefsey）治疗失败。对核苷类逆转录酶抑制剂（NRTIs）、NNRTIs、蛋白酶抑制剂（PIs）和整合酶链转移抑制剂（INSTIs）的耐药率分别为76%、86%、3%和2%。在29例对初始STR治疗失败的患者中，62%出现了对多拉韦林的耐药，而在78例换用STR后治疗失败的患者中这一比例为64%。两组之间特定NNRTI或多拉韦林耐药相关突变的发生率无显著差异。携带K65R突变的患者更有可能出现NNRTI耐药（p = 0.037）和多拉韦林耐药（p < 0.001）。
我们的研究结果显示，接受基于NNRTI的STR治疗失败的患者中多拉韦林交叉耐药率较高。在接受NNRTI治疗失败的患者中，应谨慎使用多拉韦林作为挽救治疗方案。
