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The Body Covers: The 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy

A Look at Tenofovir Drug-Drug Interactions

Coverage provided by Paul E. Sax, M.D.

September 16, 2003

Tenofovir (TDF, Viread) is generally a well tolerated medication with a low pill burden and demonstrates potent antiretroviral activity. These characteristics have led to its widespread use in clinical practice. Unlike other NRTIs, however, tenofovir use is associated with several drug interactions, most notably the reduction in levels of atazanavir (ATV, Reyataz) and an increase in levels of ddI (didanosine, Videx). These pharmacokinetic studies presented here explore further potential drug interactions related to tenofovir, specifically related to lopinavir/ritonavir (LPV/r, Kaletra), abacavir (ABC, Ziagen) and oral contraceptives.

The triple-NRTI combination of tenofovir, abacavir and 3TC (lamivudine, Epivir) has shown surprisingly poor antiviral activity in two prospective studies: a single-arm study presented previously at this year's IAS meeting in Paris (for a summary of this study, click here), and a comparative study presented at ICAAC. Potential (but still unproven) explanations for this include: 1) a tenofovir-abacavir pharmacokinetic drug interaction; 2) intracellular interaction, such as competition for a critical intracellular enzyme; or 3) low barrier to resistance via the K65R mutation. This pharmacokinetic study explored the first of these potential explanations.

Eight non-HIV-infected volunteers received a single 300-mg dose of abacavir while receiving either no other treatment or tenofovir 300-mg daily. Tenofovir and abacavir concentrations in plasma were measured, with calculated Cmax, Cmin, and area under the curve. The results showed that abacavir plasma levels were not affected by tenofovir, and that similarly, tenofovir levels did not differ from historical controls.

The results of this small pilot study suggest it is unlikely that a tenofovir-abacavir drug interaction is the cause of the suboptimal antiviral responses seen in abacavir-tenofovir-3TC treated patients, and that other explanations should be pursued. Furthermore, it enables clinicians to use abacavir and tenofovir together as part of a more comprehensive salvage regimen using other active drugs.

The above three studies provide important data on use of tenofovir with three commonly used drugs. The precise mechanism of action accounting for the various tenofovir drug interactions remains under investigation, as does the explanation for the suboptimal response to the abacavir-tenofovir-3TC regimen.

Read the poster or view the slide show of abstract A-1615.

Read the poster or view the slide show of abstract A-1617.

Read the poster or view the slide show of abstract A-1618.

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