title: Zidovudine phosphorylation determined sequentially over 12 months in human immunodeficiency virus-infected patients with or without previous exposure to antiretroviral agents.
abstract: We sought to determine whether the intracellular activation of zidovudine (ZDV) varied over time and with previous antiretroviral exposure in human immunodeficiency virus-infected individuals and to examine whether there is an association between virological responses and intracellular phosphorylation. A total of 23 patients (12 treatment naïve, 11 previously treated with ZDV) who commenced ZDV as part of dual nucleoside therapy were prospectively monitored for 12 months or until withdrawal from the study. No association was observed between virological responses at 2 weeks and 3 months and ZDV phosphorylation. The mean intracellular concentrations of ZDV mono-, di-, and triphosphates did not change significantly over time or with previous ZDV exposure. The rate of formation of total ZDV phosphates was increased in patients with CD4 counts <100 cells/mm(3). Previous reports from in vitro cell culture experiments or cross-sectional cohort studies suggesting alterations of ZDV phosphorylation over time are not confirmed by this longitudinal study.
authors.affiliation: Department of Pharmacology & Therapeutics, University of Liverpool, Liverpool L69 3GE, United Kingdom. patrick@liv.ac.uk
authors.forename: P G
authors.initials: PG
authors.lastname: Hoggard
authors.forename: J
authors.initials: J
authors.lastname: Lloyd
authors.forename: S H
authors.initials: SH
authors.lastname: Khoo
authors.forename: M G
authors.initials: MG
authors.lastname: Barry
authors.forename: L
authors.initials: L
authors.lastname: Dann
authors.forename: S E
authors.initials: SE
authors.lastname: Gibbons
authors.forename: E G
authors.initials: EG
authors.lastname: Wilkins
authors.forename: C
authors.initials: C
authors.lastname: Loveday
authors.forename: D J
authors.initials: DJ
authors.lastname: Back
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000378:metabolism* / Q000494:pharmacology; D054306:Dideoxynucleotides; D005260:Female; D006678:HIV / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D013942:Thymine Nucleotides / Q000032:analysis; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D054306:Dideoxynucleotides; D013942:Thymine Nucleotides; C057287:3'-azido-3'-deoxythymidine 5'phosphate; D015215:Zidovudine; C052873:zidovudine triphosphate