Shafer Robert W
Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California 94305, USA.
Clin Microbiol Rev. 2002 Apr;15(2):247-77. doi: 10.1128/CMR.15.2.247-277.2002.
There are 16 approved human immunodeficiency virus type 1 (HIV-1) drugs belonging to three mechanistic classes: protease inhibitors, nucleoside and nucleotide reverse transcriptase (RT) inhibitors, and nonnucleoside RT inhibitors. HIV-1 resistance to these drugs is caused by mutations in the protease and RT enzymes, the molecular targets of these drugs. Drug resistance mutations arise most often in treated individuals, resulting from selective drug pressure in the presence of incompletely suppressed virus replication. HIV-1 isolates with drug resistance mutations, however, may also be transmitted to newly infected individuals. Three expert panels have recommended that HIV-1 protease and RT susceptibility testing should be used to help select HIV drug therapy. Although genotypic testing is more complex than typical antimicrobial susceptibility tests, there is a rich literature supporting the prognostic value of HIV-1 protease and RT mutations. This review describes the genetic mechanisms of HIV-1 drug resistance and summarizes published data linking individual RT and protease mutations to in vitro and in vivo resistance to the currently available HIV drugs.
有16种已获批的1型人类免疫缺陷病毒（HIV-1）药物，分属三类作用机制：蛋白酶抑制剂、核苷和核苷酸逆转录酶（RT）抑制剂以及非核苷RT抑制剂。HIV-1对这些药物产生耐药性是由蛋白酶和RT酶（这些药物的分子靶点）发生突变所致。耐药性突变最常出现在接受治疗的个体中，这是在病毒复制未被完全抑制的情况下选择性药物压力导致的结果。然而，带有耐药性突变的HIV-1毒株也可能传播给新感染的个体。三个专家小组建议，应使用HIV-1蛋白酶和RT药敏试验来辅助选择HIV药物治疗方案。尽管基因检测比典型的抗菌药敏试验更为复杂，但有大量文献支持HIV-1蛋白酶和RT突变的预后价值。本综述描述了HIV-1耐药性的遗传机制，并总结了已发表的数据，这些数据将单个RT和蛋白酶突变与对现有HIV药物的体外和体内耐药性联系起来。
