The chemotherapeutic agent bleomycin in a two-drug combination with zidovudine, ritonavir or indinavir synergistically inhibits HIV Type-1 replication in peripheral blood lymphocytes.
It has been suggested that the combination of cancer chemotherapy with antiviral therapy is helpful for the containment of lymphomas in HIV-infected patients. Since we have recently shown that the nucleic acid binding chemotherapeutic agent bleomycin in itself has antiviral properties, we looked to see if there was any possible synergy with current anti-HIV agents. Combinations of zidovudine, indinavir or ritonavir with bleomycin, synergistically inhibited HIV-1(AT) replication in stimulated peripheral blood lymphocytes (combination index at 50% virus inhibition was 0.427, 0.604 and 0.535, respectively) and this synergism was not accompanied by any synergistic effects on cytotoxicity. We conclude from these data that further studies to investigate the clinical efficacy of combinations of antiviral and cancer chemotherapeutic agents are warranted in relation to viral load improvement.
Georgiou
N A
NA
Department of Internal Medicine, Room F02.126, University Medical Center Utrecht, Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.
van der Bruggen
T
T
Jansen
C A
CA
Oudshoorn
M
M
Nottet
H S
HS
Marx
J J
JJ
van Asbeck
B S
BS
D019380:Anti-HIV Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019469:Indinavir / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000821:virology; D008826:Microbial Sensitivity Tests; D019438:Ritonavir / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology*
D019380:Anti-HIV Agents; D000903:Antibiotics, Antineoplastic; D004338:Drug Combinations; D001761:Bleomycin; D015215:Zidovudine; D019469:Indinavir; D019438:Ritonavir