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Antimicrobial Agents and Chemotherapy, March 2001, p. 976-980, Vol. 45, No. 3
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.35.3.976-980.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Zidovudine Phosphorylation Determined Sequentially over 12 Months in Human Immunodeficiency Virus-Infected Patients with or without Previous Exposure to Antiretroviral Agents

Patrick G. Hoggard,1,* Judy Lloyd,1 Save H. Khoo,1 Michael G. Barry,1,2 Louise Dann,3 Sara E. Gibbons,1 Edmund G. Wilkins,4 Clive Loveday,3 and David J. Back1

Department of Pharmacology & Therapeutics, University of Liverpool, Liverpool L69 3GE,1 Department of Retrovirology, The Royal Free Hospital School of Medicine, London, NW3 2QG,3 and Department of Infectious Diseases, North Manchester General Hospital, Manchester M8 5RB,4 United Kingdom, and Trinity College of Health Sciences, Department of Pharmacology & Therapeutics, St. James' Hospital, Dublin, Ireland2

Received 18 August 2000/Returned for modification 26 October 2000/Accepted 30 November 2000

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/mm3. 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.

* Corresponding author. Mailing address: Department of Pharmacology & Therapeutics, University of Liverpool, Liverpool L69 3GE, United Kingdom. Phone: 44 151 794 5565. Fax: 44 151 794 5540. E-mail: patrick{at}liv.ac.uk

Antimicrobial Agents and Chemotherapy, March 2001, p. 976-980, Vol. 45, No. 3
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.35.3.976-980.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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