Selective inhibition of HIV replication by adriamycin in macrophages but not in lymphocytes

Adriamycin (ADR) is an anticancer drug commonly used in the treatment of HIV-related cancers. Due to its effect on DNA metabolism, ADR might be able to modulate HIV replication in monocyte-macrophages (M/M), resting cells potentially less sensitive to the toxic effect of this drug. Thus, we assessed the efficacy of ADR against HIV replication in both lymphocytes and M/M. We further investigated the mechanism(s) of action of ADR and its potential synergistic activity with zidovudine (AZT) or alpha-interferon (IFNα). ADR consistently inhibited viral replication in M/M: 50% viral inhibition was obtained with 0.005 μg/ml ADR, while >90% viral inhibition was obtained with 0.05 μg/ml ADR. No cell toxicity was seen in M/M at concentrations up to 0.5 μg/ml. No anti-HIV activity was shown by ADR in lymphocytes at concentrations up to 0.05 μg/ml, that is also the toxic dose 50% (TCID50 for these cells). ADR neither inactivates HIV virions nor affects HIV binding with CD4 receptors. No inhibition of HIV reverse tran...