A Preliminary Evaluation of Nelfinavir Mesylate, an Inhibitor of Human Immunodeficiency Virus (HIV)‐1 Protease, to Treat HIV Infection
| Autor: | Geoffrey J. Yuen, Amy Hendricks, Margarita Duran, William J. Hoskins, Joanna Peterkin, Marcus A. Conant, Arlene Hurley, David D. Ho, Martin Markowitz, Sharon Chapman, Amy Patick, Rosemary Schluger, Neil Clendeninn |
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| Rok vydání: | 1998 |
| Předmět: |
Adult
Male Anti-HIV Agents medicine.medical_treatment HIV Infections Virus Acquired immunodeficiency syndrome (AIDS) medicine Humans Immunology and Allergy Nelfinavir Protease biology Drug Resistance Microbial HIV Protease Inhibitors medicine.disease biology.organism_classification Virology CD4 Lymphocyte Count Infectious Diseases Enzyme inhibitor Lentivirus HIV-1 biology.protein Drug Evaluation RNA Viral Female Viral disease Follow-Up Studies medicine.drug Nelfinavir mesylate |
| Zdroj: | The Journal of Infectious Diseases. 177:1533-1540 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1086/515312 |
| Popis: | 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)-1 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 log10 reduction in HIV RNA, accompanied by a mean increase in CD4 cells of 180 ‐ 200/mm 3 . 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. The treatment of human immunodeficiency virus (HIV) in- Each of these drugs, however, has inherent limitations because |
| Databáze: | OpenAIRE |
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