Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.
STRATEGIES FOR THE PHARMACOLOGICAL INTERVENTION AGAINST HTLV-III/LAV
AIDS: Modern Concepts and Therapeutic Challenges. Broder S, ed. New York, Marcel Dekker, p. 335-60, 1987.. Unique Identifier : AIDSLINE ICDB/89650449 Yarchoan R; Broder S; Clinical Oncology Program, NCI, Bethesda, MD
Abstract:
The rationale for the use of antiviral agents against human T-lymphotropic virus-III/lymphadenopathy-associated virus (HTLV-III/LAV) infection is discussed; a strategy is outlined that has been used to develop drugs with potential clinical application; and the status is reported of several drugs (suramin, 3'-azido-3'-deoxythymidine [AZT], ribavirin, phosphonoformate, rifabutine) that are currently being investigated. In the brief period since HTLV-III/LAV was identified as the etiological agent of AIDS, a number of drugs already have been shown to have activity against the virus and at least one, AZT, has induced immunological improvement when administered over a short period of time. The general field of antiviral drug development is in its infancy, and HTLV-III has several characteristics that make it potentially difficult to control, namely, its ability to integrate into the host genome and lie dormant, its tendency to mutate, and its ability to infect at least one organ (the brain) with limited regenerative potential. Initial clinical trials most likely will be targeted at determining whether single agents have a clinical effect. Because of the ability of HTLV-III to lie dormant and mutate, it is possible that combination drug therapy may be more effective in these patients. Using two or more drugs together may allow simultaneous interference with two steps of viral replication, lessen the chance of viral resistance developing by mutation, and permit additive antiviral activity without additive toxicity of the drugs. Such therapy has been essential in the treatment of certain cancers and Mycobacterium infections. Combination antiviral therapy depends on the finding of single antiviral agents that are effective against the virus. A good start has been made in this area. (94 Refs)
Keywords: Acquired Immunodeficiency Syndrome/*DRUG THERAPY Antimony/THERAPEUTIC USE Antiviral Agents/*THERAPEUTIC USE Cytopathogenic Effect, Viral/DRUG EFFECTS Human HIV/*DRUG EFFECTS Sarcoma, Kaposi's/DRUG THERAPY Skin Neoplasms/DRUG THERAPY Suramin/THERAPEUTIC USE Tungsten/THERAPEUTIC USE Virus Replication/DRUG EFFECTS Zidovudine/THERAPEUTIC USE MONOGRAPH REVIEW REVIEW, TUTORIAL
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Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.
