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 (IC 90 ), obtained from checkerboard titrations of compound mixtures on CEM-T4 cells infected with HIV-i 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.