Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Canada.
HIV Med. 2010 Jul 1;11(6):404-11. doi: 10.1111/j.1468-1293.2009.00806.x. Epub 2010 Feb 8.
As access to antiretroviral drugs increases in developing countries, it will become increasingly important to monitor the emergence of resistance and to define the molecular pathways involved to identify optimal therapeutic regimens.
We performed genotypic resistance testing on plasma obtained from 101 HIV-infected treatment-naïve individuals from Mali. Genotyping was carried out using the Virco protocols and HXB2 was used as the reference strain.
CRF02_AG was the most common subtype, present in 71.3% of our patient population. Other subtypes included B, C, G, CRF06_CPX, CRF09_CPX, CRF01_AE, A2/CRF16_A2D, A1 and CRF13_CPX. A total of 9.9% [95% confidence interval (CI) 6.9-12.9%] of patients had at least one resistance mutation. The prevalences of mutations conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 5% (95% CI 0.7-9.2%), 6% (95% CI 1.3-10.6%) and 0%, respectively. The most frequent mutations were T215A/Y for NRTIs and K103N/T for NNRTIs. One patient harboured three NRTI resistance mutations and one NNRTI mutation. This is the first reported case of multi-drug-resistant viral transmission in Mali. Polymorphisms at protease codons 10I/V and 33F potentially associated with resistance were observed in 18.8% and 1% of patients, respectively. Several polymorphisms in the C-terminal domain of reverse transcriptase were observed: A371V (in 63.4% of patients), G335D (76.2%), E399D (10.9%) and G333E (1%).
Primary resistance was seen in 9.9% of subjects, which is higher than previously reported in Mali. Taking into consideration other polymorphisms in protease such as L10I/V and 33F, primary resistance could reach 28.7% (95% CI 19.9-37.5%). Our study reflects the need to monitor the evolution of resistance on a regular basis and trends of transmitted resistance.
随着发展中国家获得抗逆转录病毒药物的机会增加，监测耐药性的出现以及确定涉及的分子途径以确定最佳治疗方案将变得越来越重要。
我们对来自马里的 101 名未经治疗的 HIV 感染的治疗初治个体的血浆进行了基因型耐药性检测。使用 Virco 方案进行基因分型，并用 HXB2 作为参考株。
CRF02_AG 是最常见的亚型，在我们的患者人群中占 71.3%。其他亚型包括 B、C、G、CRF06_CPX、CRF09_CPX、CRF01_AE、A2/CRF16_A2D、A1 和 CRF13_CPX。共有 9.9%（95%置信区间 [95%CI] 6.9-12.9%）的患者至少有一种耐药突变。核苷逆转录酶抑制剂（NRTIs）、非核苷逆转录酶抑制剂（NNRTIs）和蛋白酶抑制剂（PIs）耐药相关突变的发生率分别为 5%（95%CI 0.7-9.2%）、6%（95%CI 1.3-10.6%）和 0%。最常见的突变是 NRTIs 的 T215A/Y 和 NNRTIs 的 K103N/T。一名患者携带三种 NRTI 耐药突变和一种 NNRTI 突变。这是马里首例多药耐药病毒传播的报告病例。在蛋白酶编码 10I/V 和 33F 处观察到的与耐药性相关的多态性分别在 18.8%和 1%的患者中存在。在逆转录酶 C 末端结构域观察到几种多态性：A371V（在 63.4%的患者中）、G335D（76.2%）、E399D（10.9%）和 G333E（1%）。
在 9.9%的受试者中观察到原发性耐药，这高于马里以前的报告。考虑到蛋白酶中的其他多态性，如 L10I/V 和 33F，原发性耐药率可能达到 28.7%（95%CI 19.9-37.5%）。我们的研究反映了需要定期监测耐药性的演变以及传播耐药性的趋势。
