Their Additive Inhibition of Normal Human Marrow Progenitor Cells

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. Retrovir (zidovudine; 3'-azidothymidine; AZT) provides significant clinical benefit to patients at various stages of human immunodeficiency virus (HIV) disease (16, 17, 51, 55). However, AZT may induce anemia, neutropenia, and thrombocytopenia in treated AIDS patients (21, 22, 39, 53). These adverse effects are most frequently noted at higher doses and in those patients with more-advanced disease (12