In vitro Selection of Human Immunodeficiency Virus Type 1 Resistant to Ro 31-8959 Proteinase Inhibitor

Abstract

Human immunodeficiency virus type I (HIV-1) resistant to the proteinase inhibitor Ro 31–8959 has been obtained by growing HIV-IIIB in C8166 cell cultures in the presence of inhibitory concentrations of the drug. Ro 31-8959-resistant HIV-1 obtained after five passages in the presence of the drug was capable of replicating, as measured by infectious virus yield, in the presence of concentrations of Ro 31-8959 able to inhibit completely the replication of the parental HIV-IIIB. Cloning of the Ro 31–8959-resistant viral preparations revealed that a number of different strains of HIV-1 with various degrees of sensitivity to Ro 31–8959 emerged during propagation of HIV-IIIB in C8166 cells in the presence of the drug. The most resistant strain shows an ID₅₀ value of 21.8 nM that is 13.2 fold higher than the value observed in HIV-IIIB infected C8166 cells.