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.