Evaluation of novel protease inhibitors against darunavir-resistant variants of HIV type 1

评估新型蛋白酶抑制剂对达芦那韦耐药的1型HIV变异株的疗效

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Abstract

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 (r)-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 (r)-lentivector, suggesting that these PIs may be the candidates as novel antiretroviral drugs against drug-resistant variants of HIV-1.

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