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JAC Advance Access originally published online on March 10, 2006
Journal of Antimicrobial Chemotherapy 2006 57(5):806-809; doi:10.1093/jac/dkl045
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Leading article

Suboptimal CD4 gains in HIV-infected patients receiving didanosine plus tenofovir

Pablo Barreiro and Vincent Soriano*

Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain

* Corresponding author. Tel: +34-91-4532500; Fax: +34-91-7336614; E-mail: vsoriano{at}dragonet.es

The combination of nucleos(t)ide analogues (NAs) is essential for the design of effective antiretroviral regimens. Although there are currently many options for the selection of such drug backbones, not all combinations display optimal results. As the number of these compounds has increased, it has become clear that the concomitant administration of certain NAs should be avoided due to high rates of toxicity and/or greater risk of virological failure. As an example, the combination of didanosine and tenofovir has recently been associated with a paradoxical depletion of CD4+ T cells in the face of complete viral suppression. Interference between the pathways leading to the intracellular activation of didanosine and tenofovir, and their blocking of the purine nucleoside phosphorylase, seems to explain this phenomenon.

Keywords: CD4+ T lymphocytes , purines , purine nucleoside phosphorylase


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