ENHANCING AZIDOTHYMIDINE ACTION ON RETROVIRUS INFECTION

THIS PROJECT WILL STUDY THE POTENTIATION OF THE INHIBITORY EFFECT OF AZIDOTHYMIDINE (AZT) ACTION TO RETROVIRUS INFECTION IN NIH 3T3 CELLS. FIRST, IT WILL BE DETERMINED WHETHER THE CONREX PHARMACEUTICAL CORPORATION'S PERMEATION ENHANCER HAS ANY IN VITRO TOXICITY TO 3T3 CELLS, MACROPHAGES, AND T AND B LYMPHOCYTES. IT WILL SUBSEQUENTLY BE DETERMINED WHETHER THE ENHANCER AFFECTS THE FUNCTIONS OF MACROPHAGES AND T AND B LYMPHOCYTES. ONCE IT HAS BEEN ESTABLISHED THAT THE ENHANCER WILL NOT ADVERSELY AFFECT THE IMMUNOLOGICALLY IMPORTANT CELLS (I.E., MACROPHAGES AND T AND B LYMPHOCYTES), THE STUDY WILL BE EXTENDED TO EVALUATE THE POTENTIATION OF THE INHIBITORY EFFECT OF AZT BY THE ENHANCER IN NIH 3T3 CELLS IN A MODEL SYSTEM. GP70 EXPRESSION, REVERSE TRANSCRIPTASE ACTIVITY, AND VIRUS TITER IN AZT-TREATED FV-INFECTED NIH 3T3 CELL CULTURES IN THE PRESENCE AND ABSENCE OF THE ENHANCER WILL BEEVALUATED. THESE DATA WILL LEAD TO THE DESIGN OF A FORMULATION TO REDUCE THE QUANTITY OF AZT REQUIRED FOR AIDS PATIENT TREATMENT, AND HENCE REDUCE THE ADVERSE SIDE EFFECTSOF AZT AND IMPROVE ITS THERAPEUTIC INDEX.