Fleury Herve J, Toni Thomas, Lan N T H, Hung P V, Deshpande Alaka, Recordon-Pinson Patricia, Boucher Sebastien, Lazaro Estibaliz, Jauvin Valerie, Lavignolle-Aurillac Valerie, Lebel-Binay Sophie, Cheret Arnaud, Masquelier Bernard
Laboratoire de Virologie UPRES EA 2968, Université de Bordeaux 2, 33076 Bordeaux France.
AIDS Res Hum Retroviruses. 2006 Apr;22(4):357-66. doi: 10.1089/aid.2006.22.357.
Non-B HIV-1 viruses are predominant in developing countries where access to antiretroviral drugs (ARVs) is progressively being intensified. It is important to obtain more data on the susceptibility of these viruses to available ARVs. CRF01_AE, CRF02_AG, and subtype C strains of HIV-1 obtained from untreated patients from Vietnam, Cote d'Ivoire, and India were analyzed for their in vitro susceptibility to NRTIs, NNRTIs, PIs, and an entry inhibitor (T-20) using a recombinant viral assay (PHENOSCRIPT). The corresponding viruses, which had been previously sequenced in reverse transcriptase (RT), protease (prot), plus envelope (env) C2/V3 genes and had therefore been fully characterized, were further sequenced in env HR1 + HR2 regions. CRF01_AE isolates are sensitive to NRTIs and NNRTIs with the exception of one isolate that exhibits a decreased susceptibility to NNRTIs associated with a I135T substitution in RT. CRF02_AG and subtype C viruses are sensitive to NRTIs and NNRTIs but some CRF02_AG isolates tend to be resistant to abacavir, potentially related to associated substitutions of RT at positions 123 (D123N) plus 135 (I135V). Whereas all but one CRF01_AE isolates are fully susceptible to PIs, some CRF02_AG and, more frequently, some subtype C isolates are resistant to atazanavir. The role of substitutions in prot at positions of secondary resistance mutations 20, 36, 63, and 82 is raised with a potentially crucial role of the V82I substitution. Finally, all viruses tested, regardless of the CRF or subtype, are fully susceptible to T-20.
在抗逆转录病毒药物（ARV）获取情况日益强化的发展中国家，非B型HIV-1病毒占主导地位。获取更多关于这些病毒对现有ARV药物敏感性的数据很重要。使用重组病毒检测法（PHENOSCRIPT），对从越南、科特迪瓦和印度未经治疗的患者中分离出的HIV-1的CRF01_AE、CRF02_AG和C亚型毒株进行了体外对核苷类逆转录酶抑制剂（NRTIs）、非核苷类逆转录酶抑制剂（NNRTIs）、蛋白酶抑制剂（PIs）和一种进入抑制剂（T-20）的敏感性分析。之前已对相应病毒的逆转录酶（RT）、蛋白酶（prot）以及包膜（env）C2/V3基因进行了测序，因此已得到充分表征，随后又对env HR1 + HR2区域进行了测序。CRF01_AE分离株对NRTIs和NNRTIs敏感，但有一个分离株除外，该分离株对NNRTIs的敏感性降低，与RT中的I135T替换有关。CRF02_AG和C亚型病毒对NRTIs和NNRTIs敏感，但一些CRF02_AG分离株往往对阿巴卡韦耐药，这可能与RT在123位（D123N）加135位（I135V）的相关替换有关。除一个CRF01_AE分离株外，所有其他分离株对PIs均完全敏感，一些CRF02_AG分离株，更常见的是一些C亚型分离株对阿扎那韦耐药。在prot的二线耐药突变位点20、36、63和82处替换的作用被提及，其中V82I替换可能起关键作用。最后，所有测试的病毒，无论属于哪种CRF或亚型，对T-20均完全敏感。
