In vitro inhibition of the infectivity and replication of human immunodeficiency virus type 1 by combination of antiretroviral 2',3'-dideoxynucleosides and virus-binding inhibitors.
We tested the in vitro inhibitory activities of three 2',3'-dideoxynucleosides and two inhibitors of viral binding in combinations against the infectivity and cytopathic effect of human immunodeficiency virus type 1. 3'-Azido-2',3'-dideoxythymidine, 2',3'-dideoxyinosine, or 2',3'-dideoxycytidine, combined with recombinant soluble CD4 (sCD4), brought about synergistic antiretroviral activity without toxicity at clinically achievable concentrations. Combinations of 2',3'-dideoxynucleosides plus dextran sulfate exerted similar synergistic antiviral effects without concomitant increases in toxicities. When sCD4 and dextran sulfate were combined, apparent antagonism was observed. We confirmed that no combination of sCD4 plus 3'-azido-2',3'-dideoxythymidine, 2',3'-dideoxyinosine, or 2',3'-dideoxycytidine significantly increased the inhibitory effect on colony formation of human myeloid-monocytic bone marrow cells in vitro at the concentrations used in this study. These data might have clinical relevance for the treatment of patients infected with human immunodeficiency virus.
Clinical Oncology Program, National Cancer Institute, Bethesda, Maryland 20892.
S
S
Hayashi
R L
RL
Fine
T C
TC
Chou
M J
MJ
Currens
S
S
Broder
H
H
Mitsuya
D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D001855:Bone Marrow Diseases / Q000139:chemically induced; D015704:CD4 Antigens / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology; D016049:Didanosine / Q000494:pharmacology; D015224:Dideoxynucleosides / Q000494:pharmacology* / Q000633:toxicity; D004357:Drug Synergism; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D011994:Recombinant Proteins / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D015704:CD4 Antigens; D003911:Dextrans; D015224:Dideoxynucleosides; D011994:Recombinant Proteins; D016264:Dextran Sulfate; D016049:Didanosine