A Preliminary Evaluation of Nelfinavir Mesylate, an Inhibitor of Human Immunodeficiency Virus (HIV)-l Protease, to Treat HIV Infection

A phase I/II dose-ranging open-label 28-day monotherapy study of the safety, pharmacokinetics, and antiviral activity of nelfinavir mesylate (Viracept), an inhibitor of human immunodeficiency virus (HIV)-l protease, was done in 65 HIV-1-infected subjects. After 28 days, 54 responding subjects entere...

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Bibliographic Details
Published in:The Journal of infectious diseases 1998-06, Vol.177 (6), p.1533-1540
Main Authors: Markowitz, Martin, Conant, Marcus, Hurley, Arlene, Schluger, Rosemary, Duran, Margarita, Peterkin, Joanna, Chapman, Sharon, Patick, Amy, Hendricks, Amy, Yuen, Geoffrey J., Hoskins, William, Clendeninn, Neil, Ho, David D.
Format: Article
Language:English
Subjects:
AIDS
Antiretrovirals
Antivirals
Blood plasma
Dosage
HIV
HIV 1
HIV infections
Major Articles
Protease inhibitors
RNA
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Summary:A phase I/II dose-ranging open-label 28-day monotherapy study of the safety, pharmacokinetics, and antiviral activity of nelfinavir mesylate (Viracept), an inhibitor of human immunodeficiency virus (HIV)-l protease, was done in 65 HIV-1-infected subjects. After 28 days, 54 responding subjects entered an open-label extension that allowed for the addition of nucleoside inhibitors of reverse transcriptase and dose escalation to maintain durability. The drug was well-tolerated and demonstrated robust antiviral activity, with demonstrable superiority of the 750 mg and 1000 mg three times daily regimens. Thirty subjects who continued to receive therapy at 12 months attained a persistent 1.6 logto reduction in HIV RNA, accompanied by a mean increase in CD4 cells of 180-200/mm³. Studies of viral genotype and phenotype after virus rebound revealed that the initial active site mutation allowing for nelfinavir resistance is mediated by a unique amino acid substitution in the HIV-1 protease D30N, which does not confer in vitro phenotypic cross-resistance to the currently available protease inhibitors.
ISSN:0022-1899