To evaluate the pharmacokinetic interaction between tenofovir and didanosine when used in combination as a highly active antiretroviral therapy regimen. Literature retrieval was accessed through MEDLINE (1966-January 2003) using the terms tenofovir and didanosine. Abstracts from recent meetings, including the International AIDS Society, Interscience Conference on Antimicrobial Agents and Chemotherapy, and the Infectious Diseases Society of America, were reviewed for relevant abstracts and poster presentations. Pharmacokinetic studies evaluating the concurrent use of tenofovir and didanosine have been performed in healthy volunteers. Tenofovir 300 mg administered concurrently with 400 mg didanosine results in a 48-64% increase in the didanosine maximum plasma concentration and AUC with no significant alterations in the tenofovir pharmacokinetic parameters. Tenofovir 300 mg and didanosine 250 mg has been compared with didanosine 400 mg alone. The results demonstrated equivalent didanosine AUCs. When used concurrently, tenofovir significantly increases the maximum plasma concentration and the AUC of didanosine. Additional data in HIV-infected patients are needed to determine the long-term toxicities of this combination therapy. Didanosine dose reduction should be considered when these 2 agents are used concurrently.