IMMUNOLOGIC APPROACHES TO THE THERAPY OF HIV-1 INFECTION

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An intensive effort was directed toward studying the potential therapeutic aspects of immunologic approaches to human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome. Adoptive immunotherapy utilizing peripheral blood lymphocytes and bone marrow from gpl60-primed syngeneic donors in association with combination antiretroviral agents was continued. One of three recipients demonstrated persistent elevations in CD4 counts after adoptive transfer. A phase I clinical trial administering a nef-specific CTL clone to its donor with IL-2 infusions was initiated. The CTL infusions were well tolerated, and modest antiretroviral activity was observed. Active immunotherapy protocols utilizing gpl60 and p24 immunogens in seropositive patients were continued. Both recombinant proteins were well tolerated and produced lymphoproliferative responses. A study generating random recombinatorial libraries of human immunoglobulin genes from HIV infected individuals was initiated in an effort to produce human monoclonal antibodies for use in passive immunotherapy. Phase I studies of the combinations of zidovudine (ZDV) and interleukin-2 (IL-2) and interferon-alpha and IL-2 were continued. The maximum tolerated dose of IL-2 when administered with ZDV has been defined, and the study has been modified to evaluate the immunologic and antiviral effects of the repeated administration of these agents. A protocol evaluating the safety and pharmacokinetics of N-acetylcysteine is nearing completion. No new toxicities have been observed, and oral bioavailability appears so low that oral dosing may be impractical. No antiretroviral effects have been seen.