Mulu Andargachew, Maier Melanie, Liebert Uwe Gerd
Institute of Virology, Faculty of Medicine, Leipzig University, Leipzig, Germany; Department of Microbiology, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.
Institute of Virology, Faculty of Medicine, Leipzig University, Leipzig, Germany.
PLoS One. 2015 Oct 29;10(10):e0141318. doi: 10.1371/journal.pone.0141318. eCollection 2015.
The emergence of HIV-1 drug resistance mutations has mainly been linked to the duration and composition of antiretroviral treatment (ART), as well as the level of adherence. This study reports the incidence and pattern of acquired antiretroviral drug resistance mutations and long-term outcomes of ART in a prospective cohort from Northwest Ethiopia. Two hundred and twenty HIV-1C infected treatment naïve patients were enrolled and 127 were followed-up for up to 38 months on ART. ART initiation and patients' monitoring was based on the WHO clinical and immunological parameters. HIV viral RNA measurement and drug resistance genotyping were done at baseline (N = 160) and after a median time of 30 (IQR, 27-38) months on ART (N = 127). Viral suppression rate (HIV RNA levels ≤ 400 copies/ml) after a median time of 30 months on ART was found to be 88.2% (112/127), which is in the range for HIV drug resistance prevention suggested by WHO. Of those 15 patients with viral load >400 copies/ml, six harboured one or more drug resistant associated mutations in the reverse transcriptase (RT) region. Observed NRTIs resistance associated mutations were the lamivudine-induced mutation M184V (n = 4) and tenofovir associated mutation K65R (n = 1). The NNRTIs resistance associated mutations were K103N (n = 2), V106M, Y181S, Y188L, V90I, K101E and G190A (n = 1 each). Thymidine analogue mutations and major drug resistance mutations in the protease (PR) region were not detected. Most of the patients (13/15) with virologic failure and accumulated drug resistance mutations had not met the WHO clinical and/or immunological failure criteria and continued the failing regimen. The incidence and pattern of acquired antiretroviral drug resistance mutations is lower and less complex than previous reports from sub Saharan Africa countries. Nevertheless, the data suggest the need for virological monitoring and resistance testing for early detection of failure. Moreover, adherence reinforcement will contribute to improving overall treatment outcomes.
HIV-1耐药性突变的出现主要与抗逆转录病毒治疗(ART)的持续时间、组成以及依从性水平有关。本研究报告了埃塞俄比亚西北部一个前瞻性队列中获得性抗逆转录病毒药物耐药性突变的发生率和模式以及ART的长期结果。招募了220例初治的HIV-1C感染患者,其中127例接受了长达38个月的ART随访。ART的启动和患者监测基于世界卫生组织的临床和免疫学参数。在基线时(N = 160)以及ART治疗中位时间30(四分位间距,27 - 38)个月后(N = 127)进行了HIV病毒RNA测量和耐药基因分型。在ART治疗中位时间30个月后,病毒抑制率(HIV RNA水平≤400拷贝/ml)为88.2%(112/127),这处于世界卫生组织建议的预防HIV耐药性的范围内。在那些病毒载量>400拷贝/ml的15例患者中,6例在逆转录酶(RT)区域携带一个或多个耐药相关突变。观察到的与核苷类逆转录酶抑制剂(NRTIs)耐药相关的突变是拉米夫定诱导的突变M184V(n = 4)和替诺福韦相关的突变K65R(n = 1)。与非核苷类逆转录酶抑制剂(NNRTIs)耐药相关的突变是K103N(n = 2)、V106M、Y181S、Y188L、V90I、K101E和G190A(各n = 1)。未检测到胸苷类似物突变和蛋白酶(PR)区域的主要耐药突变。大多数发生病毒学失败和累积耐药性突变的患者(13/15)未达到世界卫生组织的临床和/或免疫学失败标准,并继续使用无效方案。获得性抗逆转录病毒药物耐药性突变的发生率和模式低于撒哈拉以南非洲国家先前的报告且复杂性更低。然而,数据表明需要进行病毒学监测和耐药性检测以早期发现治疗失败。此外,加强依从性将有助于改善总体治疗结果。