Abstract:
A status report on the development of antiviral therapy for human T-cell lymphotropic virus type III (HTLV-III)-induced diseases is presented. In particular, the theoretical basis is outlined for using antiviral agents in AIDS (acquired immunodeficiency syndrome). A strategy is described for identifying drugs that may be clinically useful, and the difficulties in determining whether an antiviral agent is clinically beneficial in patients with AIDS are described. In addition, several drugs under investigation are described, at least one of which--3-azido-3'-deoxythymidine (AZT)--has yielded immunological and clinical benefits during short-term administration, although it is still too early to know whether such short-term gains will have a lasting impact on the course of the disease. In the 2 years since HTLV-III was shown to be the etiologic agent of AIDS, almost a dozen drugs have been shown to have in vitro activity against this virus, and several of these are being evaluated in clinical trials. Most of them are believed to act by inhibition of reverse transcriptase, and several were originally studied in animal retroviral systems: suramin, HPA 23, AZT, dideoxycytidine, ribavirin, phosphonoformate, rifabutine, and drugs other than nucleoside analogs or reverse transcriptase inhibitors. In September 1986, the randomized double-blind placebo-controlled multicenter trial of AZT in patients with AIDS (who had Pneumocystis carinii pneumonia) or poor prognosis ARC (AIDS-related complex) was terminated prematurely by the Data Safety Monitoring Board because of a significant difference in mortality between patients taking AZT and those who received placebo; after 2-6 mo on the study, 1 of 140 patients taking AZT had died compared to 19 of 135 patients on placebo. Based on these results, AZT is being made available under a Treatment IND to AIDS patients who have had P carinii pneumonia and do not have other serious opportunistic infections. (119 Refs)
Keywords: Acquired Immunodeficiency Syndrome/*DRUG THERAPY Antimony/THERAPEUTIC USE Antiviral Agents/*THERAPEUTIC USE Human HIV/DRUG EFFECTS Nucleosides/THERAPEUTIC USE Suramin/THERAPEUTIC USE Thymidine/*ANALOGS & DERIVATIVES/THERAPEUTIC USE Tungsten/THERAPEUTIC USE Virus Replication/DRUG EFFECTS MONOGRAPH REVIEW REVIEW, TUTORIAL
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