Combinations of isoprinosine and 3'-azido-3'-deoxythymidine in lymphocytes infected with human immunodeficiency virus type 1.

Since clinical trials are being planned with the immunomodulating drug isoprinosine combined with the antiviral drug 3'-azido-3'-deoxythymidine (AZT) in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex, it is important to determine the type of antiviral interaction produced by these drugs in vitro. Such a combined modality may not only produce enhanced antiviral effects but also may have a valuable immunorestorative action. The interaction of several ratios of AZT and isoprinosine on the replication of human immunodeficiency virus type 1 in human peripheral blood mononuclear cells was determined by reverse transcriptase assay of disrupted virus obtained from supernatants of cells that were exposed to virus and the drugs separately and in combination and by a human immunodeficiency virus type 1 p24 enzyme immunoassay of the same supernatants. The correlation between the reverse transcriptase and enzyme immunoassay data was high. The antiviral activity of AZT alone was neither diminished nor augmented when AZT was used in combination with isoprinosine. Isoprinosine did not enhance virus yield when used alone or in combination with AZT in peripheral blood mononuclear cells, nor did it affect the growth of uninfected cells. The in vitro results indicate that this combination did not decrease the efficacy of AZT or exacerbate virus replication.