Today’s lecture focused on the complex drug-drug interactions of coinfected patients (HCV/HIV) who undergo treatment for HCV with the new protease inhibitors. First, a bit of background: since the introduction of antiretroviral therapy, the number of deaths from HIV/AIDS has plummeted, while the incidence of deaths from end stage liver disease has skyrocketed. This is because the time to cirrhosis in a coinfected patient (vs. a HCV monoinfected patient) is significantly shorter, on the order of 10 vs. 23 years.
Therefore, treating these patients should be a priority. Relying on liver transplant is not a great strategy. We’ve learned recently that post-transplant survival of coinfected patients is below average, particularly if 1) they need a liver-kidney transplant, 2) their BMI is < 21, 3) the donor liver is HCV+ and 4) donor liver comes from an older patient.
When considering the initiation of a PI, raltegravir poses the least risk for drug-drug interaction. However, it has a low-threshold of HIV resistance so should not be used for someone with a history of HIV drug resistance. Also, before starting the PI, you must think about several other potential drug-drug interactions in commonly used drugs, such as methadone, viagra, statins, antibiotics etc.
Lastly, we also talked about use of PI in the post-transplant setting. One important take home message was that with the initiation of a PI, you can expect the FK level of tacrolimus to skyrocket. Therefore, tacrolimus should be dosed very low (o.5 mg) and only once or twice weekly. This is best done with close monitoring in a hospital. The use of boceprevir has not been well-studied in the post-transplant setting (with PI) and no data was available for review.