Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.
THE LIFE-CYCLE OF HUMAN IMMUNODEFICIENCY VIRUS AS A GUIDE TO THE DESIGN OF NEW THERAPIES FOR AIDS
AIDS: Etiology, Diagnosis, Treatment, and Prevention. Second Edition. DeVita VT Jr et al, eds. Philadelphia, Lippincott, p. 79-86, 1988.. Unique Identifier : AIDSLINE ICDB/89650901 Broder S; Clinical Oncology Program, Div. of Cancer Treatment, NCI,; Bethesda, MD
Abstract:
Possible therapeutic interventions can be based on the emerging knowledge of the life cycle of the human immunodeficiency virus that causes AIDS and its related disorders. The characteristics of HIV as a retrovirus (cell binding and entry, integration, latency and reactivation, and protein production and assembly) are described, and the actions of dideoxynucleosides and 3'-azido-2',3'-dideoxythymidine (AZT, Retrovir) are discussed. 2',3'-Dideoxynucleosides analogs can be metabolized to become potent chain-terminating inhibitors of HIV reverse transcriptase. Even at large viral doses, these analogs can inhibit completely in vitro HIV replication and its capacity to destroy T-cell cultures at concentrations that are 10-20 times lower than those that impair the proliferation and survival of target cells. 2',3'-Dideoxycytidine has the capacity to suppress HIV replication in vivo as measured by p24 antigenemia. The dose-limiting toxicity is a painful peripheral neuropathy. The author's working explanation for the activity of dideoxynucleosides against pathogenic retroviruses is that, following anabolism to nucleoside-5'-triphosphates, they bind to viral DNA polymerase and/or bring about a selective chain termination as the RNA form of the virus attempts to make DNA copies of itself. AZT represents a first step in developing practical chemotherapy against pathogenic human retroviruses. Moreover, the development of AZT is a validation of the key assumptions underlying antiviral strategies against established AIDS: HIV replication can be suppressed in vivo and such suppression can lead to prolonged survival and improved quality of life for patients with HIV infections. (61 Refs)
Keywords: Acquired Immunodeficiency Syndrome/*DRUG THERAPY/MICROBIOLOGY Dideoxynucleosides/THERAPEUTIC USE DNA, Viral/GENETICS Human HIV/GENETICS/*PHYSIOLOGY/PATHOGENICITY Receptors, Virus/PHYSIOLOGY RNA-Directed DNA Polymerase/ANTAGONISTS & INHIB Transcription, Genetic/DRUG EFFECTS *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.
