The anti-human immunodeficiency virus (HIV) activity and hemopoietic toxicity of zidovudine (AZT) and didanosine (dideoxyinosine; ddl), alone and in combination, were assessed in a variety of cell types. AZT was more potent than ddl as an inhibitor of HIV in vitro. Synergistic inhibition of HIV by the combination of these agents was observed in MT4 cells, peripheral blood lymphocytes, and macrophages. Toxicity assessment in vitro by using progenitor (erythroid and granulocyte-macrophage) colony-forming assays with normal human bone marrow showed ddI to be less toxic than AZT. Addition of inhibitory concentrations of ddI to AZT resulted in additive inhibition of progenitor CFUs. These in vitro findings suggest that combinations of ddl and AZT at appropriately modified doses may provide an enhanced degree of selectivity in anti-HIV chemotherapy.

Tissue macrophages are recognized as a cellular target for infection with the human immunodeficiency virus type 1 (HIV-1). To characterize the nature of this cell-retrovirus interaction within the lower respiratory tract we analyzed fluid and cells obtained by bronchoalveolar lavage (BAL) of eight individuals with acquired immunodeficiency syndrome (AIDS) who were undergoing diagnostic fiberoptic bronchoscopy. Of these eight individuals, seven had active infection with Pneumocystis carinii; one had suspected cytomegalovirus pneumonitis. At the time of study two were receiving the antiretroviral drug zidovudine (azidothymidine [AZT]). HIV-1 could not be isolated from any of the eight samples of BAL fluid concentrated by ultracentrifugation through 20% sucrose. HIV-1 antigen (p24) was detected in one of eight samples of concentrated BAL fluid but could not be found in eight samples of media conditioned by overnight incubation with adherent BAL cells. Despite the infrequent detection of HIV-1 antigen it was possible to identify HIV-1 genomic sequences by the use of a DNA amplification technique, the polymerase chain reaction, in all eight BAL cell preparations. In BAL cells adherent for up to 5 days in culture this method detected retroviral DNA that hybridized to a complementary pair of primers located in the env and gag gene regions of HIV-1. These studies demonstrate the uniform presence of HIV-1 harboring cells within the airways of the lung in individuals with AIDS and active respiratory infection and may have implications for local organ defense.(ABSTRACT TRUNCATED AT 250 WORDS)