LITHIUM AND ANTIVIRAL DRUG TOXICITY .1. FURTHER-STUDIES ON THE ABILITY OF LITHIUM TO MODULATE THE HEMATOPOIETIC TOXICITY ASSOCIATED WITH THE ANTIVIRAL DRUG ZIDOVUDINE (AZT)

Lithium influences many aspects of blood cell production, in particula r, the formation of granulocytes. Lithium has been demonstrated to be an effective agent whenever granulocyte production is either faulty or inadequate. The antiviral drug zidovudine (AZT) has been used extensi vely in the treatment of acquired immune deficiency syndrome (AIDS). I ts effectiveness is limited because of associated myelosuppression and bone marrow toxicity. We have previously demonstrated that lithium, w hen combined with AZT in vitro with normal bone marrow cells or when a dministered in vivo to mice receiving dose-escalation AZT, reduced the myelosuppression and marrow toxicity of AZT significantly. Further st udies evaluated lithium's capacity to modulate AZT toxicity by investi gating the ability of lithium to influence blood cell production when administered to normal mice following an initial exposure to AZT. C57B L6 were administered dose-escalation AZT (1.0 mg/ml and 2.5 mg/ml) for a period of 4-weeks. This was followed by an additional 4-week period during which mice received continued AZT with the addition of lithium carbonate (1 mM). Animals were analyzed weekly for their peripheral b lood indices. Animals receiving AZT showed anemia, thrombocytopenia, a nd neutropenia which was dose-related. During combination lithium/AZT, there was significantly less anemia, thrombocytopenia, and neutropeni a. These studies provide further evidence supporting the potential rol e that lithium might play in the treatment of HIV-infected patients re ceiving anti-viral therapy.