SYNERGISTIC INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INVITRO BY INTERFERON ALPHA AND COUMERMYCIN-A1

Interferon alpha, either leukocyte derived or the recombinant form, and the DNA gyrase inhibitor coumermycin Al both inhibited human immunodeficiency virus type 1 (HIV) replication in vitro. We have found that combinations of these two agents synergistically inhibited HIV replication in human peripheral blood leucocytes (PBL). Significant inhibition was detected when both virion-associated reverse transcriptase activity and p24 levels were used as markers of replication. Mathematical analysis of data using the procedure of Chou and Chou (1987) produced combination indices of less than 1.0 for most effect levels at several combination ratios. Synergy was also evident when the classical isobologram technique was used for data analysis. Synergistic drug interactions were observed at concentrations not associated with cytotoxicity or anti-proliferative effects, and were seen at concentrations achievable in vivo.