Bleomycin has antiviral properties against drug-resistant HIV strains and sensitises virus to currently used antiviral agents.

In this study we performed phenotypic assays to assess involvement of the cancer chemotherapeutic agent bleomycin (BLM) in replication inhibition of mutant HIV-1 viral strains. Three clinically relevant mutant HIV variants, including one containing the Q151M mutation conferring multinucleoside resistance, were equally as sensitive to BLM as the wild-type HXB2 strain. Long-term incubation of BLM with a wild-type HIV(Ba-L) strain did not alter the sensitivity of the strain to BLM (IC(50) of BLM 0.64 microM at the beginning of incubation to 0.58 microM). At the same point in time, resistance to lamivudine (3TC) and zidovudine (AZT) was noted. Interestingly, the BLM-treated virus showed hypersensitivity to both AZT and 3TC. Our results suggest a contribution of BLM in viral load reduction in patients receiving both anticancer and antiviral agents and harbouring both wild-type and resistant HIV strains.

Mechanism of inhibition of the human immunodeficiency virus type 1 by the oxygen radical generating agent bleomycin.

Alternative targets of attack of the human immunodeficiency virus (HIV) are necessary in light of infection persistence due to onset of resistance after conventional reverse transcriptase and protease inhibitor therapy. We have recently shown that the cancer chemotherapeutic agent bleomycin (BLM) dose-dependently inhibits HIV-1 replication. The mechanism of this viral inhibition in vitro was investigated. Cell-free wild-type virions were affected directly by BLM in the presence of H2O2, as shown by a 38% decrease of viral infectivity. Viral inhibition by BLM did not proceed via NF-kappaB inhibition. The viral R/U5 DNA product was reduced by 70% without any effect on reverse transcriptase activity. In both a cell-free system as well as two-cell systems the antiviral dependence of BLM on iron and oxidant species was demonstrated. Bleomycin seems to inhibit HIV-1 replication through the same properties that make it a suitable anti-cancer agent. The results presented in this study describe a novel mechanism of HIV-1 inhibition with potential application in viral infections. The anti-HIV effects of BLM in patients receiving this drug in combination with HAART should be carefully monitored in order to evaluate the clinical significance of the findings described in this study.