Low prevalence of doravirine-associated resistance mutations among polish human immunodeficiency-1 (HIV-1)-infected patients.

IF 1.3 4区 医学 Q4 INFECTIOUS DISEASES
Kaja Scheibe, A. Urbańska, P. Jakubowski, M. Hlebowicz, M. Bociąga-Jasik, A. Raczyńska, A. Szymczak, B. Szetela, W. Łojewski, M. Parczewski
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引用次数: 3

Abstract

INTRODUCTION 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. METHODS 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. RESULTS 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%; p = 0.0013) and rilpivirine (5.40%; p < 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%; p < 0.0001) and NVP (26.0%; p < 0.0001). CONCLUSIONS 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.
波兰人免疫缺陷病毒1型(HIV-1)感染患者中多拉韦林相关耐药性突变的低患病率。
多啦韦林(DOR)是一种新型的非核苷逆转录酶抑制剂(NNRTI),对常见的NNRTI耐药性突变保持活性。在这项研究中,我们旨在调查波兰有经验和天真的HIV-1感染治疗患者中DOR耐药性突变与其他NNRTI耐药性突变的患病率。方法在两个数据集中评估对DOR和其他NNRTI的耐药性:1760名接受抗逆转录病毒治疗的幼稚HIV-1患者和200名有治疗经验的患者。所有1960个序列都是使用批量测序从患者中获得的。耐药性分析采用斯坦福大学HIV耐药性数据库评分。结果总体而言,32例(1.62%)患者存在DOR耐药性,其中13例(0.74%)为幼稚患者,19例(9.50%)有治疗经验。在幼稚患者中观察到的最常见的DOR耐药性突变是A98G和K101E(各0.2%),而在经历cART的患者中,这些突变是L100I(2.0%)、K101E、V108I、H221Y和P225H(各1.5%)。此外,在幼稚患者中,观察到对DOR的常见耐药性(0.7%)低于对奈韦拉平(NVP)(2.1%;p=0.0013)和利匹韦林(5.40%;p<0.0001)。从有治疗经验的患者获得的序列中,对DOR的耐药性发生率(9.5%)低于依非韦伦(25.5%;p<0.0001)和NVP(26.0%;p<0.001)。结论对DOR传播耐药性的发生率较低,可以有效治疗未接受抗逆转录病毒治疗的患者并快速开始治疗。在有cART经验的患者中,这种药物仍然是一种有吸引力的NNRTI选择,具有更高的耐药性遗传屏障。
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来源期刊
Antiviral Therapy
Antiviral Therapy 医学-病毒学
CiteScore
2.60
自引率
8.30%
发文量
35
审稿时长
4-8 weeks
期刊介绍: Antiviral Therapy (an official publication of the International Society of Antiviral Research) is an international, peer-reviewed journal devoted to publishing articles on the clinical development and use of antiviral agents and vaccines, and the treatment of all viral diseases. Antiviral Therapy is one of the leading journals in virology and infectious diseases. The journal is comprehensive, and publishes articles concerning all clinical aspects of antiviral therapy. It features editorials, original research papers, specially commissioned review articles, letters and book reviews. The journal is aimed at physicians and specialists interested in clinical and basic research.
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