ANTIVIRAL SYNERGY BETWEEN INHIBITORS OF HIV PROTEINASE AND REVERSE-TRANSCRIPTASE

Ro 31-8959, a potent and specific inhibitor of HIV proteinases, is shown to interact synergistically in combination with nucleoside analogue inhibitors of HIV reverse transcriptase (AZT, ddC, 2'-FddC). Ninety per cent inhibition endpoints (IC90), obtained from checkerboard titrations of compound mixtures on CEM-T4 cells infected with HIV-1 strain GB8, have been further analysed. Compared with concentrations needed when inhibitors are used individually, reductions of between 2- and 30-fold were observed in combination, depending on the nucleoside analogue and the ratio of concentrations employed. The results suggest that combinations of AZT or ddC with Ro 31-8959 should be considered for development as candidate antiviral treatments of patients with HIV infection.