Budayanti Nyoman Sri, Merati Tuti Parwati, Bela Budiman, Mahardika Gusti Ngurah
Microbiology Department, Faculty of Medicine, Udayana University, Jl. PB Sudirman, Denpasar, Bali, Indonesia.
Internal Medicine Department, Faculty of Medicine, Udayana University, Jl. PB Sudirman, Denpasar, Bali, Indonesia.
Curr HIV Res. 2018;16(5):374-382. doi: 10.2174/1570162X17666190204101154.
Molecular epidemiological study of human immunodeficiency virus drugresistant (HIVDR) markers is challenging in areas where the dominant subtype is non-B.
Here we provide molecular data for HIVDR in the CRF01_AE subtype in Bali, Indonesia.
Seventy patients were enrolled in this study and grouped into treatment failure and treatment naïve groups. The full-length pol gene was amplified using nested reverse transcriptase polymerase chain reaction and the product was then sequenced. The readable sequence was then subjected to Stanford HIV Drug Resistance Database genotyping.
We found that clinical classification was in accordance with the presence of HIVDR markers in the pol gene. Independent of therapy history, the treatment failure group showed resistance markers against nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI), ranging from 72%-100% of patients. Only a small proportion of naïve patients harbored HIV with drug resistance markers to NNRTI. No protease inhibitor-resistant marker was found in either patient group. Molecular marker mutations, which were found in more than 50% of treatment failure patients, were M184V (100%), T215A/Y/F (88.2%), D67N/G (76.5%), and M41L (58.8%).
The protocol used in this study to determine genetic markers of HIVDR based on subtype B can be applied for the rapid determination of resistance of the CRF01_AE subtype. All patients with progressive clinical signs and increased viral load should be recommended to undergo second-line treatment of the ARV regimen.
在主要亚型为非B型的地区,对人类免疫缺陷病毒耐药(HIVDR)标志物进行分子流行病学研究具有挑战性。
在此,我们提供印度尼西亚巴厘岛CRF01_AE亚型HIVDR的分子数据。
本研究纳入70例患者,分为治疗失败组和初治组。使用巢式逆转录聚合酶链反应扩增全长pol基因,然后对产物进行测序。将可读序列提交至斯坦福HIV耐药数据库进行基因分型。
我们发现临床分类与pol基因中HIVDR标志物的存在情况相符。无论治疗史如何,治疗失败组中对核苷类逆转录酶抑制剂(NRTI)和非核苷类逆转录酶抑制剂(NNRTI)显示耐药标志物的患者比例为72%-100%。只有一小部分初治患者携带对NNRTI有耐药标志物的HIV。在两组患者中均未发现蛋白酶抑制剂耐药标志物。在超过50%的治疗失败患者中发现的分子标志物突变有M184V(100%)、T215A/Y/F(88.2%)、D67N/G(76.5%)和M41L(58.8%)。
本研究中基于B亚型确定HIVDR基因标志物的方案可用于快速确定CRF01_AE亚型的耐药性。所有具有进行性临床体征和病毒载量增加的患者均应建议接受抗逆转录病毒治疗方案的二线治疗。