Sargin Altunok Elif, Sayan Murat, Akhan Sila, Aygen Bilgehan, Yildiz Orhan, Tekin Koruk Suda, Mistik Resit, Demirturk Nese, Ural Onur, Kose Şükran, Aynioglu Aynur, Korkmaz Fatime, Ersoz Gülden, Tuna Nazan, Ayaz Celal, Karakecili Faruk, Keten Derya, Inan Dilara, Yazici Saadet, Koculu Safiye, Yildirmak Taner
Infectious Diseases and Clinical Microbiology, Bitlis Public Hospital, Bitlis 13000, Turkey.
Clinical Laboratory, Kocaeli University Faculty of Medicine, Kocaeli 41380, Turkey; Near East University, Research Center of Experimental Health Sciences, Nicosia, Northern Cyprus.
Int J Infect Dis. 2016 Sep;50:1-5. doi: 10.1016/j.ijid.2016.07.003. Epub 2016 Jul 9.
Drug resistance development is an expected problem during treatment with protease inhibitors (PIs), this is largely due to the fact that Pls are low-genetic barrier drugs. Resistance-associated variants (RAVs) however may also occur naturally, and prior to treatment with Pls, the clinical impact of this basal resistance remains unknown. In Turkey, there is yet to be an investigation into the hepatitis C (HCV) drug associated resistance to oral antivirals.
178 antiviral-naïve patients infected with HCV genotype 1 were selected from 27 clinical centers of various geographical regions in Turkey and included in the current study. The basal NS3 Pls resistance mutations of these patients were analyzed.
In 33 (18.5%) of the patients included in the study, at least one mutation pattern that can cause drug resistance was identified. The most frequently detected mutation pattern was T54S while R109K was the second most frequently detected. Following a more general examination of the patients studied, telaprevir (TVR) resistance in 27 patients (15.2%), boceprevir (BOC) resistance in 26 (14.6%) patients, simeprevir (SMV) resistance in 11 (6.2%) patients and faldaprevir resistance in 13 (7.3%) patients were detected. Our investigation also revealed that rebound developed in the presence of a Q80K mutation and amongst two V55A mutations following treatment with TVR, while no response to treatment was detected in a patient with a R55K mutation.
We are of the opinion that drug resistance analyses can be beneficial and necessary in revealing which variants are responsible for pre-treatment natural resistance and which mutations are responsible for the viral breakthrough that may develop during the treatment.
在使用蛋白酶抑制剂（PIs）治疗期间，耐药性的产生是一个预期会出现的问题，这主要是因为PIs是低遗传屏障药物。然而，耐药相关变异（RAVs）也可能自然发生，在使用PIs治疗之前，这种基础耐药性的临床影响尚不清楚。在土耳其，尚未对丙型肝炎（HCV）药物相关的口服抗病毒药物耐药性进行调查。
从土耳其不同地理区域的27个临床中心选取178例初治的HCV基因1型感染患者纳入本研究。分析这些患者的基础NS3 PIs耐药突变。
在纳入研究的患者中，有33例（18.5%）至少检测到一种可导致耐药的突变模式。最常检测到的突变模式是T54S，而R109K是第二常检测到的。在对研究患者进行更全面的检查后，检测到27例患者（15.2%）存在替拉瑞韦（TVR）耐药，26例患者（14.6%）存在博赛匹韦（BOC）耐药，11例患者（6.2%）存在simeprevir（SMV）耐药，13例患者（7.3%）存在法达瑞韦耐药。我们的研究还发现，在使用TVR治疗后，Q80K突变以及两个V55A突变之一的情况下会出现病毒反弹，而一名携带R55K突变的患者未检测到治疗反应。
我们认为耐药性分析有助于揭示哪些变异导致治疗前的自然耐药，哪些突变导致治疗期间可能出现的病毒突破，因此是有益且必要的。
