Gallant Joel E, Gerondelis Peter Z, Wainberg Mark A, Shulman Nancy S, Haubrich Richard H, St Clair Marty, Lanier Ernest R, Hellmann Nicholas S, Richman Douglas D
The Johns Hopkins University, Baltimore, Md., USA.
Antivir Ther. 2003 Dec;8(6):489-506.
Although advances in highly active antiretroviral therapy (HAART) have made long-term suppression of HIV an achievable goal of therapy, a substantial proportion of first-line regimens will eventually fail. Successful longterm treatment requires consideration of downstream treatment options at the time of initiating or changing regimens. An understanding of the patterns and interactions of resistance mutations, and the appropriate use of genotypic and phenotypic testing is an important component of successful drug sequencing. Resistance to multiple nucleoside reverse transcriptase inhibitors (NRTIs) may result from several genotypically distinct pathways, including the Q151M (151 complex), the 69 insertion complex, two distinct thymidine analogue mutational pathways and the K65R mutation. Knowledge of the clinical implications of these and other resistance pathways, as well as the antagonism or synergy between mutations, helps guide individualized treatment choices from initial therapy in the treatment-naive patient to salvage therapy in the highly treatment-experienced individual. The development of effective sequencing strategies will depend upon the continued understanding of drug resistance mutation patterns and their associations with specific HAART combinations. This review summarizes research advances that further the understanding of nucleoside and nucleotide analogue resistance mutations, and their interplay.
尽管高活性抗逆转录病毒疗法（HAART）的进展已使长期抑制HIV成为可实现的治疗目标，但相当一部分一线治疗方案最终会失败。成功的长期治疗需要在开始或改变治疗方案时考虑后续的治疗选择。了解耐药突变的模式和相互作用，以及基因型和表型检测的合理使用，是成功进行药物排序的重要组成部分。对多种核苷类逆转录酶抑制剂（NRTIs）的耐药可能由几种基因型不同的途径引起，包括Q151M（151复合体）、69插入复合体、两种不同的胸苷类似物突变途径以及K65R突变。了解这些及其他耐药途径的临床意义，以及突变之间的拮抗或协同作用，有助于指导从初治患者的初始治疗到高度经治个体的挽救治疗的个体化治疗选择。有效排序策略的发展将取决于对耐药突变模式及其与特定HAART组合之间关联的持续了解。本综述总结了有助于进一步理解核苷和核苷酸类似物耐药突变及其相互作用的研究进展。
