Vergne L, Peeters M, Mpoudi-Ngole E, Bourgeois A, Liegeois F, Toure-Kane C, Mboup S, Mulanga-Kabeya C, Saman E, Jourdan J, Reynes J, Delaporte E
Laboratoire Retrovirus, IRD, Montpellier, France.
J Clin Microbiol. 2000 Nov;38(11):3919-25. doi: 10.1128/JCM.38.11.3919-3925.2000.
Most human immunodeficiency virus (HIV) drug susceptibility studies have involved subtype B strains. Little information on the impact of viral diversity on natural susceptibility to antiretroviral drugs has been reported. However, the prevalence of non-subtype-B (non-B) HIV type 1 (HIV-1) strains continues to increase in industrialized countries, and antiretroviral treatments have recently become available in certain developing countries where non-B subtypes predominate. We sequenced the protease and reverse transcriptase (RT) genes of 142 HIV-1 isolates from antiretroviral-naive patients: 4 belonged to group O and 138 belonged to group M (9 subtype A, 13 subtype B, 2 subtype C, 5 subtype D, 2 subtype F1, 9 subtype F2, 4 subtype G, 5 subtype J, 2 subtype K, 3 subtype CRF01-AE, 67 subtype CRF02-AG, and 17 unclassified isolates). No major mutations associated with resistance to nucleoside reverse transcriptase inhibitors (NRTIs) or protease inhibitors were detected. Major mutations linked to resistance to non-NRTI agents were detected in all group O isolates (A98G and Y181C) and in one subtype J virus (V108I). In contrast, many accessory mutations were found, especially in the protease gene. Only 5.6% of the 142 strains, all belonging to subtype B or D, had no mutations in the protease gene. Sixty percent had one mutation, 22.5% had two mutations, 9.8% had three mutations, and 2.1% (all group O strains) had four mutations. In order of decreasing frequency, the following mutations were identified in the protease gene: M36I (86.6%), L10I/V (26%), L63P (12.6%), K20M/R (11.2%), V77I (5.6%), A71V (2.8%), L33F (0.7%), and M46I (0.7%). R211K, an accessory mutation associated with NRTI resistance, was also observed in 43.6% of the samples. Phenotypic and clinical studies are now required to determine whether multidrug-resistant viruses emerge more rapidly during antiretroviral therapy when minor resistance-conferring mutations are present before treatment initiation.
大多数人类免疫缺陷病毒（HIV）药物敏感性研究都涉及B亚型毒株。关于病毒多样性对抗逆转录病毒药物天然敏感性影响的信息报道较少。然而，在工业化国家，非B亚型HIV-1毒株的流行率持续上升，并且在某些以非B亚型为主的发展中国家，抗逆转录病毒治疗最近已可供使用。我们对142例未接受过抗逆转录病毒治疗患者的HIV-1分离株的蛋白酶和逆转录酶（RT）基因进行了测序：4株属于O组，138株属于M组（9株为A亚型，13株为B亚型，2株为C亚型，5株为D亚型，2株为F1亚型，9株为F2亚型，4株为G亚型，5株为J亚型，2株为K亚型，3株为CRF01-AE重组亚型，67株为CRF02-AG重组亚型，17株为未分类分离株）。未检测到与对核苷类逆转录酶抑制剂（NRTIs）或蛋白酶抑制剂耐药相关的主要突变。在所有O组分离株（A98G和Y181C）以及1株J亚型病毒（V108I）中检测到与对非核苷类逆转录酶抑制剂耐药相关的主要突变。相比之下，发现了许多辅助性突变，尤其是在蛋白酶基因中。142株毒株中只有5.6%（均属于B亚型或D亚型）的蛋白酶基因没有突变。60%有1个突变，22.5%有2个突变，9.8%有3个突变，2.1%（均为O组毒株）有4个突变。按频率递减顺序，在蛋白酶基因中鉴定出以下突变：M36I（86.6%）、L10I/V（26%）、L63P（12.6%）、K20M/R（11.2%）、V77I（5.6%）、A71V（2.8%）L33F（0.7%）和M46I（0.7%）。在43.6%的样本中还观察到与NRTI耐药相关的辅助性突变R211K。现在需要进行表型和临床研究，以确定在治疗开始前存在微小耐药性突变时，多药耐药病毒在抗逆转录病毒治疗期间是否会更快出现。
