• Amprenavir (APV) and Ritonavir (RTV): Intra-Individual Comparison of Different Doses and Influence of Concomitant NNRTI on Steady-State Pharmacokinetics in HIV-Infected Patients (Poster 739)
  Authored by O. Degen, M. Kurowski, J. Van Lunzen, C. K. Schewe, and H.-J. Stellbrink
  View the original abstract

The use of low-dose ritonavir with amprenavir lowers the pill burden and significantly increases the drug level, improving the usefulness of amprenavir, both among protease-naive and protease-experienced patients. But efavirenz and nevirapine lower the levels of amprenavir. What happens when the three drugs are used together, as is often used in salvage regimens?

In this paper, German investigators examined the three-way interaction with non-nukes with two different combinations of ritonavir and amprenavir. The two regimens were the commonly used 600mg amprenavir with 100mg ritonavir, as well as amprenavir 450mg with 200mg ritonavir. The 450/200 dose was used initially, then either nevirapine or efavirenz were added. In 5/17 patients, the combination was then changed to 600/100 and levels were re checked.

The trough levels were lower in all of the patients when changed to 600/100. The investigators conclude that 100 mg of ritonavir may not be enough to counteract the effects of adding a non nuke, especially efavirenz. This phenomenon would be more likely to be an issue in salvage therapy.

This is a small study, and the design is not as rigorous as some. However, the results are consistent with what one might expect. It is reasonable to ask if 600/200 might not be a better regimen when a non-nuke is added in salvage regimens, but this combination was not studied. The uncertainty of these three-way interactions is a potential use of therapeutic drug monitoring in the future.