Kantor Rami, Fessel W Jeffrey, Zolopa Andrew R, Israelski Dennis, Shulman Nancy, Montoya Jose G, Harbour Michael, Schapiro Jonathan M, Shafer Robert W
Division of Infectious Diseases and AIDS Research, Stanford University, Stanford, California 94301, USA.
Antimicrob Agents Chemother. 2002 Apr;46(4):1086-92. doi: 10.1128/AAC.46.4.1086-1092.2002.
In order to track the evolution of primary protease inhibitor (PI) resistance mutations in human immunodeficiency virus type 1 (HIV-1) isolates, baseline and follow-up protease sequences were obtained from patients undergoing salvage PI therapy who presented initially with isolates containing a single primary PI resistance mutation. Among 78 patients meeting study selection criteria, baseline primary PI resistance mutations included L90M (42% of patients), V82A/F/T (27%), D30N (21%), G48V (6%), and I84V (4%). Despite the switching of treatment to a new PI, primary PI resistance mutations present at the baseline persisted in 66 of 78 (85%) patients. D30N persisted less frequently than L90M (50% versus 100%, respectively; P < 0.001) and V82A/F/T (50% versus 81%, respectively; P = 0.05). HIV-1 isolates from 38 (49%) patients failing PI salvage therapy developed new primary PI resistance mutations including L90M, I84V, V82A, and G48V. Common combinations of primary and secondary PI resistance mutations after salvage therapy included mutations at amino acid positions 10, 82, and 46 and/or 54 in 16 patients; 10, 90, and 71 and/or 73 in 14 patients; 10, 73, 84, 90, and 46 and/or 54 in 5 patients; 10, 48, and 82 in 5 patients; and 30, 88 and 90 in 5 patients. In summary, during salvage PI therapy, most HIV-1 isolates with a single primary PI resistance mutation maintained their original mutations, and 49% developed additional primary PI resistance mutations. The persistence of L90M, V82A/F/T, G48V, and I84V during salvage therapy suggests that these mutations play a role in clinical resistance to multiple PIs.
为了追踪1型人类免疫缺陷病毒（HIV-1）分离株中主要蛋白酶抑制剂（PI）耐药突变的演变情况，从接受挽救性PI治疗的患者中获取基线和随访蛋白酶序列，这些患者最初呈现含有单一主要PI耐药突变的分离株。在符合研究选择标准的78例患者中，基线主要PI耐药突变包括L90M（42%的患者）、V82A/F/T（27%）、D30N（21%）、G48V（6%）和I84V（4%）。尽管治疗更换为新的PI，但基线时存在的主要PI耐药突变在78例患者中的66例（85%）持续存在。D30N持续存在的频率低于L90M（分别为50%对100%；P<0.001）和V82A/F/T（分别为50%对81%；P = 0.05）。来自38例（49%）PI挽救治疗失败患者的HIV-1分离株出现了新的主要PI耐药突变，包括L90M、I84V、V82A和G48V。挽救治疗后主要和次要PI耐药突变的常见组合包括16例患者在氨基酸位置10、82和46和/或54处的突变；14例患者在10、90和71和/或73处的突变；5例患者在10、73、84、90和46和/或54处的突变；5例患者在10、48和82处的突变；以及5例患者在30、88和90处的突变。总之，在挽救性PI治疗期间，大多数具有单一主要PI耐药突变的HIV-1分离株维持其原始突变，49%出现了额外的主要PI耐药突变。挽救治疗期间L90M、V82A/F/T、G48V和I84V的持续存在表明这些突变在对多种PI的临床耐药中起作用。
