Synergistic inhibition of human immunodeficiency virus type 1 (HIV-1) replication in vitro by recombinant soluble CD4 and 3'-azido-3'-deoxythymidine.
A combination of antiviral therapies that target different sites in the human immunodeficiency virus type 1 (HIV-1) replicative cycle may be necessary for optimal treatment of HIV-1 infections. We evaluated the interactions of a soluble virus receptor (recombinant soluble CD4 or rsT4) and a reverse transcriptase inhibitor (azidothymidine, AZT) against HIV-1 replication in vitro. A variety of cell types was studied including peripheral blood mononuclear cells, a CD4-positive T-cell line, and a CD4-positive human monocyte cell line. The combination of rsT4 and AZT inhibited HIV-1 synergistically over a broad range of drug concentrations and multiplicities of infection in several different HIV-1 replication assays. Drug interactions were evaluated by the median-effect principle and the isobologram technique using a computer analysis. In all of the cell types tested, combinations of rsT4 and AZT were synergistic in vitro, without additive cytotoxicity.
Johnson
V A
VA
Infectious Disease Unit, Massachusetts General Hospital, Boston 02114.
Barlow
M A
MA
Chou
T C
TC
Fisher
R A
RA
Walker
B D
BD
Hirsch
M S
MS
Schooley
R T
RT
D000945:Antigens, Differentiation, T-Lymphocyte; D002999:Clone Cells; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D015728:Receptors, HIV; D011991:Receptors, Virus; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology*
D000945:Antigens, Differentiation, T-Lymphocyte; D015728:Receptors, HIV; D011991:Receptors, Virus; D011994:Recombinant Proteins; D015215:Zidovudine