title: Evaluation of novel protease inhibitors against darunavir-resistant variants of HIV type 1.
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) (DRVr-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 DRVr-lentivector, suggesting that these PIs may be the candidates as novel antiretroviral drugs against drug-resistant variants of HIV-1.
authors.affiliation: Department of International Health Kobe University Graduate School of Health Sciences Hyogo Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of International Health Kobe University Graduate School of Health Sciences Hyogo Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Oyama
authors.affiliation: Faculty of Pharmaceutical Sciences Kobe Gakuin University Hyogo Japan.
authors.forename: Koushi
authors.initials: K
authors.lastname: Hidaka
authors.affiliation: Department of International Health Kobe University Graduate School of Health Sciences Hyogo Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kameoka
keywords: HIV‐1; antiretroviral therapy; lentiviral vector; phenotypic drug susceptibility test; protease inhibitor