Anti-human immunodeficiency virus synergism by zidovudine (3'-azidothymidine) and didanosine (dideoxyinosine) contrasts with 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;ddI), alone and in combination, were assessed in a variety of cell types. AZT was more potent than ddI 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 ddI and AZT at appropriately modified doses may provide an enhanced degree of selectivity in anti-HIV chemotherapy.
Dornsife
R E
RE
Division of Experimental Therapy, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.
St Clair
M H
MH
Huang
A T
AT
Panella
T J
TJ
Koszalka
G W
GW
Burns
C L
CL
Averett
D R
DR
D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D016049:Didanosine / Q000494:pharmacology*; D004357:Drug Synergism; D015672:Erythroid Precursor Cells / Q000187:drug effects; D006678:HIV / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology*
D015215:Zidovudine; D012194:RNA-Directed DNA Polymerase; D016049:Didanosine