March 9, 2011
From CROI, March 2011: One of the main concerns with treating hepatitis C (HCV) disease in people living with HIV is the possible drug interactions among the various medicines. HCV drugs may increase or decrease the levels of HIV meds, and vice versa. At a minimum, people taking regimens for both diseases would take five to six medicines over 48 weeks.
Much is already known about the interactions of standard HCV treatment (interferon and ribavirin) with HIV meds, but less is known about the interactions from the new HCV drug telaprevir. In earlier study, blood levels of telaprevir increased 30% when using Viread (tenofovir).
In three studies reported on at CROI, telaprevir was given to HIV/HCV-negative volunteers together with the NNRTI Sustiva (efavirenz) as well as with the protease inhibitors boosted Reyataz (atazanavir), boosted Prezista (darunavir), boosted Lexiva (fosamprenavir) and Kaletra (lopinavir + ritonavir).
In the first study, telaprevir was taken for 10 days, followed by a one-day “washout”, and then it was taken with one of the protease inhibitors for 20 days. All drugs were taken with food. In the second study, the regimens were reversed. In the third, telaprevir was taken for 7 days, with a washout day, then Sustiva + Viread was taken for 7 days, which was followed by telaprevir given 3x or 2x/day with Sustiva + Viread for another 7 days. Again, telaprevir was taken with food but not with Sustiva + Viread.
The results showed that there were interactions between telaprevir and the boosted protease inhibitors. Reyataz levels only slightly increased while telaprevir levels slightly decreased, so dose adjustments are probably not needed. With the other boosted protease inhibitors — Prezista, Lexiva and Kaletra — significant interactions occurred, and the right doses are not yet known.
As for Sustiva, it reduced the blood level of telaprevir, so a higher dose of telaprevir (1,125mg vs. 750mg) could partly offset that interaction. In a separate study, ritonavir did not “boost” the effects of telaprevir, as is seen when it’s taken with HIV protease inhibitors. Both Reyataz and Sustiva are now being studied with telaprevir in co-infected individuals.
Pharmacokinetic Interactions between ARV Agents and the Investigational HCV Protease Inhibitor TVR in Healthy Volunteers. Van Heeswijk R, et al. Abstract #119.
Low-dose RTV and the Pharmacokinetics of the Investigational HCV Protease Inhibitor TVR in Healthy Volunteers. Garg V, et al. Abstract #629.