Yunnan Provincial Hospital of Infectious Disease, AIDS Care Center (YNACC), Kunming Medical University affiliated Infectious diseases hospital, 28 Shian Road, Taiping District, Kunming, 650301, China.
Virol J. 2019 Jan 8;16(1):5. doi: 10.1186/s12985-018-1112-6.
Understanding the prevalence and evolution of HIV-1 drug resistance (DR) and associated mutation patterns is critical to implementing free antiretroviral therapy in Yunnan, the first antiretroviral treatment location in China. Here We provide a basis for understanding the occurrence and development of HIV-1 resistance in Yunnan and a theoretical foundational for strategy to delay HIV-1 drug resistance and achieve successful individualized treatment.
Plasma samples from different cities/prefectures were collected at Yunnan Provincial Hospital of Infectious Disease from January 2010 to September 2016, and those from drug-resistant individuals were genotyped using in-house assays, 88 patients were selected for the study who had been on treatment for ≥6 months (and for whom drug resistance was then measured), and each patient had at least 3 genotype resistance tests and who were enrolled to analyze mutation and evolution of HIV resistance.
264 Pol sequences of 88 patients were obtained. Drug resistance levels to eight drugs increased to varying degrees with prolonged treatment. Resistance to efavirenz (EFV) and etravirine (ETR) showed the highest change, comparisons of resistant changes to second and first and to third and second agents showed altered level of drug resistance were 25 and 20 cases, 28 and 18 cases, respectively. The smallest change was Lopinavir/Ritonavir (LPV/r) present 2 and 3 cases; Resistance to lamivudine (3TC) and lopinavir/ritonavir (LPV/r) was high among patients detected thrice, whereas other drugs were distributed in all resistance levels. M184 V/I (26.14%), T69S (11.36%), and T215Y/I (10.23%) mutations were the most common in nucleoside reverse transcriptase inhibitors (NRTIs), and K103 N/R/S (21.59%), V179D/E (20.45%) in Non-NRTIs (NNRTIs). Furthermore, L10 V/F/I (6.82%), A71V (4.55%), and I54V (4.55%) mutations were common in protease inhibitors (PIs).
We found dynamic genotypic changes in HIV-1 drug-resistance in Yunnan, with prolonged treatment, and drug resistance was inevitable. However, resistance to different drugs occurred at varying times, and mutation site emergence was the main cause. These findings enhance our understanding of evolution and regulation, and are valuable for developing HIV-1 DR prevention strategies in Yunnan.
了解 HIV-1 耐药性（DR）的流行情况和演变，以及相关的突变模式，对于在中国开展免费抗逆转录病毒治疗至关重要，云南是中国第一个开始进行抗逆转录病毒治疗的地方。本研究为了解云南 HIV-1 耐药性的发生和发展提供了依据，为延迟 HIV-1 耐药性和实现个体化成功治疗的策略提供了理论基础。
2010 年 1 月至 2016 年 9 月，从云南省传染病医院收集不同城市/州的血浆样本，对耐药个体进行基因分型检测，选择 88 例治疗时间≥6 个月（并进行耐药性检测）的患者进行研究，每个患者至少进行了 3 次基因型耐药检测，以分析 HIV 耐药性的突变和演变。
共获得 88 例患者的 264 个 Pol 序列。随着治疗时间的延长，8 种药物的耐药水平呈不同程度的升高。对依非韦伦（EFV）和依曲韦林（ETR）的耐药性变化最高，与第二和第一、第三和第二种药物的耐药性变化相比，耐药性改变分别为 25 例和 20 例，28 例和 18 例。最小的变化是洛匹那韦/利托那韦（LPV/r），分别为 2 例和 3 例；检测了 3 次的患者中，拉米夫定（3TC）和洛匹那韦/利托那韦（LPV/r）耐药率较高，而其他药物则分布在所有耐药水平。核苷逆转录酶抑制剂（NRTIs）中最常见的突变是 M184V/I（26.14%）、T69S（11.36%）和 T215Y/I（10.23%），而非核苷逆转录酶抑制剂（NNRTIs）中最常见的突变是 K103N/R/S（21.59%）、V179D/E（20.45%）。此外，蛋白酶抑制剂（PIs）中常见的突变是 L10V/F/I（6.82%）、A71V（4.55%）和 I54V（4.55%）。
我们发现云南 HIV-1 耐药性随着治疗时间的延长发生了动态的基因型变化，耐药性不可避免。然而，不同药物的耐药性发生时间不同，突变位点的出现是主要原因。这些发现增强了我们对进化和调控的理解，为制定云南 HIV-1 耐药性预防策略提供了有价值的信息。
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