Scheibe Kaja, Urbańska Anna, Jakubowski Paweł, Hlebowicz Maria, Bociąga-Jasik Monika, Raczyńska Aleksandra, Szymczak Aleksandra, Szetela Bartosz, Łojewski Władysław, Parczewski Miłosz
Department of Infectious, Tropical Diseases and Immune Deficiency, 175603Pomeranian Medical University in Szczecin, Szczecin, Poland.
Pomeranian Hospital, Gdańsk, Poland.
Antivir Ther. 2021 May;26(3-5):69-78. doi: 10.1177/13596535211043044. Epub 2021 Oct 20.
Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) that retains activity against common NNRTI resistance mutations. In this study, we aimed to investigate the prevalence of DOR resistance mutations compared with that of resistance mutations for other NNRTIs among HIV-1-infected treatment-experienced and -naïve patients from Poland.
Resistance to DOR and other NNRTIs was assessed in two datasets: 1760 antiretroviral treatment-naïve HIV-1 patients and 200 treatment-experienced patients. All 1960 sequences were derived from the patients using bulk sequencing. For resistance analyses, Stanford HIV drug resistance database scores were used.
Overall, DOR resistance was present in 32 patients (1.62%), of whom 13 (0.74%) were naïve and 19 (9.50%) were treatment-experienced. The most common DOR resistance mutations observed among the naïve patients were A98G and K101E (0.2% each), and those among cART-experienced patients were L100I (2.0%), K101E, V108I, H221Y, and P225H (1.5% each). Furthermore, among the naïve patients, less common resistance to DOR (0.7%) compared with that to nevirapine (NVP) (2.1%; = 0.0013) and rilpivirine (5.40%; < 0.0001) was observed. For sequences obtained from treatment-experienced patients, the frequency of resistance to DOR (9.5%) was lower than that for efavirenz (25.5%; < 0.0001) and NVP (26.0%; < 0.0001).
The frequency of transmitted drug resistance to DOR is low, allowing for effective treatment of antiretroviral treatment-naïve patients and rapid treatment initiation. In cART-experienced patients, this agent remains an attractive NNRTI option with a higher genetic barrier to resistance.
多瑞韦（DOR）是一种新型非核苷类逆转录酶抑制剂（NNRTI），对常见的NNRTI耐药突变仍具有活性。在本研究中，我们旨在调查波兰HIV-1感染的有治疗经验和无治疗经验患者中，多瑞韦耐药突变的流行情况，并与其他NNRTI的耐药突变情况进行比较。
在两个数据集中评估对多瑞韦和其他NNRTI的耐药性：1760例未接受过抗逆转录病毒治疗的HIV-1患者和200例有治疗经验的患者。所有1960个序列均通过二代测序从患者中获得。对于耐药性分析，使用斯坦福HIV耐药数据库评分。
总体而言，32例患者（1.62%）存在多瑞韦耐药，其中13例（0.74%）为未接受过治疗的患者，19例（9.50%）为有治疗经验的患者。在未接受过治疗的患者中观察到的最常见多瑞韦耐药突变是A98G和K101E（各0.2%），在接受过cART治疗的患者中是L100I（2.0%）、K101E、V108I、H221Y和P225H（各1.5%）。此外，在未接受过治疗的患者中，与奈韦拉平（NVP）（2.1%；P = 0.0013）和利匹韦林（5.40%；P < 0.0001）相比，多瑞韦耐药的情况较少见（0.7%）。对于有治疗经验的患者获得的序列，多瑞韦耐药频率（9.5%）低于依非韦伦（25.5%；P < 0.0001）和奈韦拉平（26.0%；P < 0.0001）。
多瑞韦的传播耐药频率较低，这使得未接受过抗逆转录病毒治疗的患者能够得到有效治疗并迅速开始治疗。在接受过cART治疗的患者中，这种药物仍然是一种有吸引力的NNRTI选择，对耐药具有更高的遗传屏障。
