Synergistic drug combinations in AIDS therapy. Dipyridamole/3'-azido-3'-deoxythymidine in particular and principles of analysis in general

Combination chemotherapy has been prominent for more than a generation in the treatment of such diseases as cancer, hypertension, and bacterial infections. In the case of viral infections, combinations are coming rapidly into focus for the human immunodeficiency virus (HIV). Reasons for combination chemotherapy of HIV include synergy of antiviral effects, antagonism of toxicities, distribution of toxicities among organ systems, prevention of emergence of resistant variants, enhancement of immune function, and treatment of concurrent opportunistic infections. In the present paper two stories will be intertwined: a brief summary of our studies on combinations of the drug dipyridamole (DPM) with 3'-azido-3'-deoxythymidine (zidovudine, AZT) and other 2',3'-dideoxynucleosides; and presentation of a new approach to the analysis of drug combinations, as embodied in a computer program package called COMBO.