Consensus symposium on combined antiviral therapy; Overview of interferon and IL-2 combinations for the treatment of HIV infection

Abstract

Among the immunomodulatory cytokines that have been evaluated for the treatment of HIV disease, α-interferon and interleukin-2 (IL-2) have been the most extensively studied. Monotherapy with α-interferon is effective therapy for HIV-associated Kaposi's sarcoma (KS) in patients with CD4 counts > 150 cells/mm 3. However, the doses necessary to achieve a significant anti-tumor effect are often poorly tolerated. Combination therapy with α-interferon and zidovudine is associated with dose-limiting toxicities and an anti-tumor effect similar to that of higher dose α-interferon monotherapy. The combination of α-interferon and zidovudine can synergistically inhibit HIV replication in vitro; however, in vivo results suggest the anti-HIV effect of this combination is no greater than that seen with zidovudine monotherapy. Whether combination of interferon-α and other antiviral drugs will be useful in the treatment of HIV infection remains to be seen. Recent studies employing intermittent courses of IL-2 combined with continuous antiretroviral therapy indicate that sustained rises in CD4 counts can be achieved. The ability of IL-2 therapy to result in a sustained rise in CD4 counts is critically dependent on the pre-treatment CD4 count. The immunologic and clinical significance of these IL-2-induced increases in CD4 counts is unknown. Larger, controlled trials are currently underway to evaluate the role of intermittent IL-2 therapy in HIV infection.