Inhibition of Purified Recombinant Reverse Transcriptase from Wild-Type and Zidovudine-Resistant Clinical Isolates of Human Immunodeficiency Virus Type 1 by Zidovudine, Stavudine, and Lamivudine Triphosphates

• Published in: The Journal of infectious diseases Vol. 184; no. 10; pp. 1336 - 1340
• Main Authors: Duan, Chengying, Poticha, David, Stoeckli, Thomas C., Petropoulos, Christos J., Whitcomb, Jeannette M., McHenry, Charles S., Kuritzkes, Daniel R.
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 15.11.2001; The University of Chicago Press
• Subjects: Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antivirals; Biological and medical sciences; Codons; Concise Communications; Cross resistance; Cytidine Triphosphate - analogs & derivatives; Cytidine Triphosphate - pharmacology; Dideoxynucleotides; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Enzymes; Escherichia coli - genetics; Genetic mutation; HIV 1; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; Human immunodeficiency virus 1; Human viral diseases; Infectious diseases; Inhibitory concentration 50; Lamivudine - analogs & derivatives; Lamivudine - pharmacology; Medical sciences; Nucleosides; Pharmacology. Drug treatments; Recombinant Proteins - antagonists & inhibitors; Reverse Transcriptase Inhibitors - pharmacology; RNA-Directed DNA Polymerase - biosynthesis; RNA-Directed DNA Polymerase - genetics; Stavudine - pharmacology; Thymine Nucleotides - pharmacology; Transfection; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viruses; Zidovudine - analogs & derivatives; Zidovudine - pharmacology; Zidovudine - therapeutic use; RNA-directed DNA polymerase; HIV-1 virus; Stavudine; DNA-directed RNA polymerase; Reverse transcriptase inhibitor; Clinical isolate; Pyrimidine nucleoside; Human; Immunopathology; Enzyme; Transferases; Retroviridae; Enzyme inhibitor; Lamivudine; AIDS; Lentivirus; Immune deficiency; Infection; Virus; Resistance; Nucleotidyltransferases; Sensitivity; Viral disease; Dideoxynucleoside; Human immunodeficiency virus; Nucleosidic analog; Zidovudine
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/323995

Cross-resistance between zidovudine, stavudine, and lamivudine was studied, using purified recombinant reverse transcriptase from a zidovudine-susceptible and -resistant pair of clinical isolates of human immunodeficiency virus type 1. The zidovudine-resistant isolate exhibited low-level cross-resistance to both stavudine and lamivudine in drug susceptibility assays. Enzyme from the resistant isolate demonstrated reduced inhibition by zidovudine triphosphate and stavudine triphosphate and, to a lesser extent, lamivudine triphosphate. These findings provide additional evidence at the viral and enzyme level for cross-resistance between zidovudine and stavudine, and they suggest a possible effect of zidovudine resistance on susceptibility to lamivudine.