Consensus symposium on combined antiviral therapy; overview of interferon and IL-2 combinations for the treatment of HIV infection.
Among the immunomodulatory cytokines that have been evaluated for the treatment of HIV disease, alpha-interferon and interleukin-2 (IL-2) have been the most extensively studied. Monotherapy with alpha-interferon is effective therapy for HIV-associated Kaposi's sarcoma (KS) in patients with CD4 counts > 150 cells/mm3. However, the doses necessary to achieve a significant anti-tumor effect are often poorly tolerated. Combination therapy with alpha-interferon and zidovudine is associated with dose-limiting toxicities and an anti-tumor effect similar to that of higher dose alpha-interferon monotherapy. The combination of alpha-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-alpha 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.
Sneller
M C
MC
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D012514:Sarcoma, Kaposi / Q000188:drug therapy; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
D000998:Antiviral Agents; D016898:Interferon-alpha; D007376:Interleukin-2; D015215:Zidovudine