This project began with the discovery in our laboratory group of a new possible """"""""modulatory"""""""" combination therapy for AIDS (dideoxynucleoside plus nucleoside transport inhibitor), which we and our collaborators developed through Phase I clinical trials. When we could not find any published method appropriate for the design and analysis of our experiments on this combination therapy, we decided to develop our own. The result was a set of new concepts, algorithms, and computer programs, incorporated into a package called COMBO. The COMBO algorithms for design and analysis of combination therapy now form the central portion of this project, albeit a small fraction of overall effort in the research group. We have used the new algorithms and programs (in both cancer and AIDS research) to design and analyze experiments on combinations involving such agents as suramin, tumor necrosis factor, taxol, dipyridamole, AZT, ddI, ddC, CD4-pseudomonas exotoxin, HIV protease inhibitors, and hydroxyurea, among others. Fairly recent published analyses have included those on combinations of AZT or ddi with protease inhibitor KNI-272 (in collaboration with H. Mitsuya and colleagues, AIDS Research and Human Retroviruses 1994;38:1036) and on combinations of dideoxynucleosides and hydroxyurea (in collaboration with R. Gallo and colleagues, e.g., Science 1994;266:801).
