IMMUNE-BASED THERAPEUTICS - SCIENTIFIC RATIONALE AND THE PROMISING APPROACHES TO THE TREATMENT OF THE HUMAN-IMMUNODEFICIENCY-VIRUS INFECTEDINDIVIDUAL

The primary approach to therapy for infection with human immunodeficie ncy virus (HIV) continues to be centered around antiretroviral agents that have conferred significant clinical benefits. The considerable de gree of immunologic dysfunction in HIV infection, however, has led to intense interest in methods of immune stimulation and reconstitution. Immunomodulatory intervention in HIV infection is highly controversial . Over the years a number of immunomodulatory agents-many with only a poor rationale for their clinical use-have been evaluated. In this rev iew we concentrate on immunomodulatory approaches that are currently b eing investigated. We group these interventions, reviewing the rationa le and clinical data for each category: passive immunity (administrati on of immunoglobulins and use of apheresis), thymic hormone treatment, cytokine treatment (administration of interleukins, tumor necrosis fa ctor, and interferons), adoptive cellular immunity, and therapeutic va ccination. At present, the only interventions supported by data from w ell-controlled studies are the parenteral administration of interferon alpha to patients with HIV-associated Kaposi's sarcoma and the admini stration of pooled immunoglobulin (to decrease the rate of bacterial i nfections) to children who cannot take trimethoprim-sulfamethoxazole. However, several other approaches under development show promise in re versing some of the immune deficits of HIV infection. Clinical evaluat ion of these approaches should yield valuable insights into the immuno pathogenesis of HIV infection, and these insights should facilitate th e formulation of new modalities of treatment.