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The optimal use of biological response modifiers (BRMs) in human immunodeficiency virus (HIV)-related disease depends on knowledge of the molecular basis of the immune deficiencies and dysregulations that occur during the course of the infection; evidence for the role of viral products and cytokines in the suppression of immune function is discussed. Immunebased therapies are currently being explored alone and in combination with drugs targeted to HIV and associated opportunistic infections and malignancies. These therapies include hematopoietic growth factors for the management of drug toxicities, cytokines, antigen- and cell-based therapies, and synthetic immunomodulators. The entry of additional BRMs into clinical trials for HIV-disease can be facilitated by well-designed preclinical studies that address special problems related to the disease. including the need for concomitant therapy for the spectrum of disease manifestations encountered.

The goal of a prophylactic human immunodeficiency (HIV) vaccine is to elicit immune response(s) that will, upon subsequent exposure to HIV. prevent lnfection and/or disease. On the other hand. therapeutic administration of a vaccine to an individual in whom infection is already established might benefit the individual by augmenting existing functional immune responses or inducing new ones. Development of vaccines for the prevention of AIDS offers unique challenges. Concerns regarding the safely of attenuated and whole-killed products have led to the pursuit of alternativc designs. including recombinant proteins, vectors and particles, synthetic peptides and naked DNA. Seven recombinant envelope. two recombinant vector and four other candidate vaccines that have entered into phase 1 trials in noninfected individuals have proven safe to date, and have differed In their ability lo induce functional antibody and Cytotoxic T lymphocytes. Two recombinant envelope products have recently progressed to phase 2 testing, Five envelope-based and six other products have entered trial in HIV-infected and individuals and have appeared to be safe, Evidence of new antibody, increased T cell proliferation and lncreased cytotoxic T lymphocyte activity have been reported. Additional placebo controlled trials will be required to evaluate the impact of therapeutic vaccination on CD4 cell count. viral burdrn and clinical end-points. The status of HIV/AIDS vaccine development is reviewed. with emphasis on the challenging task of finding an effieacious, safe, prophylactic vaccine.