Caride E, Hertogs K, Larder B, Dehertogh P, Brindeiro R, Machado E, de Sá C A, Eyer-Silva W A, Sion F S, Passioni L F, Menezes J A, Calazans A R, Tanuri A
Genetic Department, UFRJ, Rio de Janeiro, Brazil.
Virus Genes. 2001;23(2):193-202. doi: 10.1023/a:1011812810397.
We have investigated the phenotypic and genotypic susceptibility of 14 HIV-1 strains isolated from individuals failing HAART therapy to protease inhibitors (PI). Proviral and plasma viral pol gene fragment were amplified, sequenced and subtyped. Nine samples clustered with protease subtype B reference strains and the remaining samples were classified as non-B subtype corresponding to subtype F (n = 4) and subtype A (n = 1). Although all patients were treated with similar P1 drug regimen, the non-B subtype isolates did not present the L90M and 184V mutations and used mainly G48V and V82A/F to achieve drug resistance. A strong cross-resistance phenotype among all four PI was associated with the mutation L90M in the subtype-B isolates, and with G48V and V82A/F in the non-B counterparts. This observation revealed that the non-B viruses tested had specific genotypic characteristics contrasting with the subtype-B isolates.
我们研究了从接受高效抗逆转录病毒治疗(HAART)失败的个体中分离出的14株HIV-1毒株对蛋白酶抑制剂(PI)的表型和基因型敏感性。对前病毒和血浆病毒pol基因片段进行扩增、测序和亚型分析。9个样本与蛋白酶B亚型参考毒株聚类,其余样本被分类为非B亚型,分别对应F亚型(n = 4)和A亚型(n = 1)。尽管所有患者均接受相似的PI药物治疗方案,但非B亚型分离株未出现L90M和184V突变,主要通过G48V和V82A/F实现耐药。B亚型分离株中的L90M突变以及非B亚型对应毒株中的G48V和V82A/F与所有四种PI之间的强交叉耐药表型相关。这一观察结果表明,所检测的非B病毒具有与B亚型分离株不同的特定基因型特征。