NEW DEVELOPMENTS IN ANTIRETROVIRAL DRUG THERAPY FOR HUMAN IMMUNODEFICIENCY VIRUS INFECTIONS

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

NEW DEVELOPMENTS IN ANTIRETROVIRAL DRUG THERAPY FOR HUMAN IMMUNODEFICIENCY VIRUS INFECTIONS

AIDS Clinical Review 1990. Volberding P and Jacobson MA, eds. New York, Marcel Dekker, p. 235-72, 1990.. Unique Identifier : AIDSLINE ICDB/91675542
Johnson VA; Hirsch MS; Dept. of Medicine, Massachusetts General Hosp., Harvard Medical; Sch., Boston, MA

Abstract: Significant strides in the development of antiretroviral therapy have been made since the first reports of drugs capable of inhibiting HIV replication appeared in 1984-1985. There is now widespread recognition that the optimal management of HIV-1 infections probably will require combination antiretroviral therapy. Highlights of recent developments in anti-HIV-1 therapy are reviewed, including zidovudine and resistance, alternative antiretroviral agents (recombinant soluble CD4, reverse transcriptase inhibitors [2',3'-dideoxycytidine; 2',3'-dideoxyinosine; and 2',3'-didehydro-2',3'-dideoxythymidine], inhibitors of glycoprotein processing, and interferons [IFNs]), and combination therapy for HIV infection (drug combinations with synergistic activity against HIV replication in vitro, combination therapy that is antagonistic in vitro, and clinical trials of combination therapy). Numerous clinical trials of combination chemotherapy are in progress including several Phase I clinical trials of combined zidovudine and IFN-alpha for AIDS patients with Kaposi's sarcoma. Dose-limiting toxicities of zidovudine and IFN-alpha have included bone marrow suppression (both neutropenia and anemia) and transaminase elevations, particularly at the highest doses tested during escalation of each component. However, antitumor and antiviral effects were seen in several trials when zidovudine and IFN-alpha were combined at lower doses, and the response to combination therapy was equivalent or better than the response to either agent alone. The future approach to chronic HIV infections likely will include combination therapy for effective, nontoxic intervention. The employment of two- and three-drug regimens, either in combination or in sequence, may represent an important development in antiretroviral therapy. (181 Refs)

Keywords: Acquired Immunodeficiency Syndrome/DRUG THERAPY Antiviral Agents/*THERAPEUTIC USE AIDS-Related Complex/DRUG THERAPY Combined Modality Therapy Human HIV/*DRUG EFFECTS HIV Envelope Protein gp120/DRUG EFFECTS HIV Envelope Protein gp41/DRUG EFFECTS HIV Infections/*DRUG THERAPY Interferons/THERAPEUTIC USE Receptors, HIV/DRUG EFFECTS RNA-Directed DNA Polymerase/ANTAGONISTS & INHIB Virus Replication/*DRUG EFFECTS Zidovudine/THERAPEUTIC USE MONOGRAPH REVIEW
911030
M91A1114

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