Inoue Mari, Oyama Daiki, Hidaka Koushi, Kameoka Masanori
Department of International Health Kobe University Graduate School of Health Sciences Hyogo Japan.
Faculty of Pharmaceutical Sciences Kobe Gakuin University Hyogo Japan.
FEBS Open Bio. 2016 Nov 24;7(1):88-95. doi: 10.1002/2211-5463.12160. eCollection 2017 Jan.
HIV disease became a manageable chronic disease since combination antiretroviral therapy (cART) was introduced as the standard treatment regimen. However, the emergence of drug-resistant viruses is a major problem associated with cART. A phenotypic drug susceptibility test using a lentiviral vector was established and applied to evaluate new protease inhibitors (PIs). Lentiviral vectors representing a wild-type (WT-lentivector) and darunavir (DRV)-resistant HIV type 1 (HIV-1) (DRV -lentivector) were generated. Nine clinically approved protease inhibitors (PIs) inhibited the transduction ability of WT-lentivector similar to their inhibitory effects on the replication of WT HIV-1. Three new PIs reduced the transduction ability of WT- and DRV -lentivector, suggesting that these PIs may be the candidates as novel antiretroviral drugs against drug-resistant variants of HIV-1.
自从联合抗逆转录病毒疗法（cART）被引入作为标准治疗方案以来，HIV疾病已成为一种可控制的慢性疾病。然而，耐药病毒的出现是与cART相关的一个主要问题。一种使用慢病毒载体的表型药物敏感性试验被建立并应用于评估新型蛋白酶抑制剂（PIs）。构建了代表野生型（WT-慢病毒载体）和对达芦那韦（DRV）耐药的1型HIV（HIV-1）（DRV-慢病毒载体）的慢病毒载体。九种临床批准的蛋白酶抑制剂（PIs）抑制WT-慢病毒载体的转导能力，类似于它们对WT HIV-1复制的抑制作用。三种新型PIs降低了WT-和DRV-慢病毒载体的转导能力，表明这些PIs可能是针对HIV-1耐药变体的新型抗逆转录病毒药物的候选药物。
