Lack of Alteration of Lopinavir and Ritonavir Through Plasma Concentrations in HIV-Experienced Patients Treated With Kaletra and Tenofovir DF

• Lack of Alteration of Lopinavir and Ritonavir Through Plasma Concentrations in HIV-Experienced Patients Treated With Kaletra and Tenofovir DF (Abstract H-1715)
  Authored by J. Poirier, J. Meynard, J. Guiard-Schmid, P. Girard, W. Rozenbaum, P. Jaillon
  Poster Presentation: View the original abstract

We have come to realize how important it is to understand drug interactions. This is particularly important with protease inhibitors, but can affect many other HIV drugs as well. Drug interactions can lead to excessively high levels of one drug, which will in turn lead to side effects or worse. Interactions can also lower a drug's levels, possibly leading to treatment failure and resistance. Testing for all the possible interactions is a daunting task, and we often do not get all of the data we need until after a drug is on the market.

This study looked at the possibility of an interaction between lopinavir/ritonavir (Kaletra) and tenofovir DF (TDF, Viread). This is important since these two drugs are often used together in the setting of patients who have failed on multiple other combinations, and small changes in drug levels could spell trouble.

Investigators from Paris looked at 10 patients with extensive prior treatment experience who were on lopinavir/ritonavir and then subsequently added tenofovir. This study was a retrospective study, taking advantage of the fact that drug levels are routinely measured in France. Five were on standard dose (three capsules twice daily or 400/100) and five were on higher dose (four capsules or 500/133) along with efavirenz (EFV, Sustiva). Roughly 62 measurements were made in all. The conclusions were refreshingly simple. The levels of lopinavir and ritonavir did not change significantly when tenofovir was added.

Thus, the simple conclusion is that no dose alteration is needed when tenofovir is added to lopinavir/ritonavir. This is not true if efavirenz or nevirapine (NVP, Viramune) is added. In that case, the recommendation is to increase the dose of lopinavir/ritonavir from three to four Kaletra capsules twice daily.

This study, of course, does not address the difficult and controversial question of whether measuring drug levels in routine practice (also called therapeutic drug monitoring or TDM) is useful, nor when to do it. In the absence of good data, our European colleagues have adopted it wholeheartedly, while in the United States it is rarely or never done. Stay tuned, I hope, for better studies that will answer whether the expense and extra blood draws may in fact be worthwhile in at least some settings.