We propose to study the potentiation of the inhibitory effect of azidothymidine (AZT) action to retrovirus infection in NIH 3T3 cells. First we shall determine whether Conrex Permeation Enhancer (CPE) has any in vitr toxicity to macrophages, T and B lymphocytes. We will subsequently determin whether CPE affects the functions of macrophages, T & B lymphocytes. Once we have established that CPE will not adversely affect the immunologically important cell, i.e. macrophages, T & B lymphocytes, we will then extend th study to evaluate the potentiation of the inhibitory effect of AZT bb CPE in NIH 3T3 cells in a model system. We will evaluate GP 70 expression, reverse transcriptase activity and virus titer in AZT-treated F-MuLV- infected NIH 3T3 cell cultures in the presence and absence of CPE. These data should allow us to design a formulation to reduce the quantity of AZT required for AIDS patient treatment, hence to reduce dramatically the adverse side-effects of AZT and improve its therapeutic index.
