Immune-based therapeutics: scientific rationale and the promising approaches to the treatment of the human immunodeficiency virus-infected individual

Abstract

The primary approach to therapy for infection with human immunodeficiency virus (HIV) continues to be centered around antiretroviral agents that have conferred significant clinical benefits. The considerable degree 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 review we concentrate on immunomodulatory approaches that are currently being investigated. We group these interventions, reviewing the rationale and clinical data for each category: passive immunity (administration of immunoglobulins and use of apheresis), thymic hormone treatment, cytokine treatment (administration of interleukins, tumor necrosis factor, and interferons), adoptive cellular immunity, and therapeutic vaccination. At present, the only interventions supported by data from well-controlled studies are the parenteral administration of interferon alpha to patients with HIV-associated Kaposi's sarcoma and the administration of pooled immunoglobulin (to decrease the rate of bacterial infections) to children who cannot take trimethoprim-sulfamethoxazole. However, several other approaches under development show promise in reversing some of the immune deficits of HIV infection. Clinical evaluation of these approaches should yield valuable insights into the immunopathogenesis of HIV infection, and these insights should facilitate the formulation of new modalities of treatment.