IN-VITRO SELECTION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 RESISTANT TO RO 31-8959 PROTEINASE-INHIBITOR

Human immunodeficiency virus type I (HIV-1) resistant to the proteinas e 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 prese nce of the drug was capable of replicating, as measured by infectious virus yield, in the presence of concentrations of Ro 31-8959 able to i nhibit 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 p resence 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 i nfected C8166 cells.