Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.
STRATEGIES AND TARGETS FOR ANTI-HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 CHEMOTHERAPY
AIDS in Children, Adolescents, and Heterosexual Adults: An Interdisciplinary Approach to Prevention. Schinazi RF, Nahmias AJ, eds. New York, Elsevier, p. 126-43, 1988.. Unique Identifier : AIDSLINE ICDB/89649787 Schinazi RF; VA Medical Center, Atlanta, GA
Abstract:
The medical, social and economic impact of AIDS and associated diseases caused by HIV and the need to identify chemotherapeutic agents is self-evident. Strategies for prophylactic and therapeutic intervention to prevent, treat and control progression of the disease require understanding of the biologic and molecular properties of HIV. Antiviral chemotherapy applied to HIV-infected persons who have AIDS or AIDS-related complex (ARC) is discussed. Topics include the population targeted for antiviral therapy, the ideal antiviral agent, virus replication, targets for antiviral drugs, viral reverse transcriptase, other enzymes involved in viral biosynthesis, drug-resistant viruses, the molecular basis for developing drugs that target cell fusion, currently available antiviral drugs (for patients (pts) with ARC and AIDS and for pts with opportunistic infections), antiviral testing, toxicity testing, animal models, mechanism of action of 3'-azido-3'-deoxythymidine (AZT; zidovudine) and other nucleoside analogs, metabolism of AZT and 2',3'-dideoxycytidine, and clinical trials of AZT. Effective drug therapy against HIV is needed both for pts with AIDS and ARC and for possible prophylaxis of individuals who are still antibody negative but may have contacts with seropositive individuals. In a multicenter, placebo-controlled trial involving 281 pts, AZT reduced the risk of mortality in certain adult AIDS and advanced ARC pts. The overall mortality rate during 36 wk of treatment was 6.2% for those receiving AZT vs almost 40% for those given a placebo. The drug significantly reduced the risk of acquiring opportunistic infections associated with AIDS, and the severity of these infections also was reduced. Among the unresolved issues in HIV chemotherapy are drug interactions that may be detrimental to the pts, drug-resistant HIV, long-term effects of drug treatment on pts, and the effects of drug therapy on the relative risk of virus transmission. (85 Refs)
Keywords: Acquired Immunodeficiency Syndrome/*DRUG THERAPY Antiviral Agents/ADVERSE EFFECTS/*THERAPEUTIC USE AIDS-Related Complex/DRUG THERAPY Clinical Trials Drug Resistance, Microbial Human HIV-1/*DRUG EFFECTS/PHYSIOLOGY RNA-Directed DNA Polymerase/ANTAGONISTS & INHIB Structure-Activity Relationship Virus Replication/DRUG EFFECTS Zidovudine/THERAPEUTIC USE CLINICAL TRIAL 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.
