Hulskotte from Merck and colleagues presented a poster looking at drug-drug
interactions between the HCV protease inhibitor boceprevir (Victrelis)
– one of the first two
approved hepatitis C DAAs
– and the widely used ritonavir-boosted HIV protease
inhibitors atazanavir (Reyataz),
darunavir (Prezista) and
In this study 39 healthy adult
volunteers with neither HCV nor HIV first received 800mg
three-times-daily boceprevir for six days. They then took 300/100mg once-daily
atazanavir/ritonavir, 600/100mg twice-daily darunavir or 400/100mg twice-daily
lopinavir/ritonavir for about two weeks, adding boceprevir during the last five
Co-administration of boceprevir with the boosted HIV
protease inhibitor was generally well-tolerated with no serious adverse events, but the
researchers saw some significant changes in blood drug levels.
Total, maximum and minimum (trough) concentrations of all
three HIV protease inhibitors fell, with decreases ranging from about 25% to
about 60%. Average total exposure (known as AUC) of atazanavir decreased by
35%, darunavir by 44% and lopinavir by 34%. Boceprevir also decreased ritonavir
exposure in all three combinations.
Co-administration with atazanavir/ritonavir did not
significantly alter total boceprevir levels. However, lopinavir/ritonavir
decreased the total concentration of boceprevir by 45% and darunavir/ritonavir
did so by 32%.
interactions had already come to light in February when
Merck issued a Dear Health Care Professional letter describing the findings and
stating that the company "does not recommend" co-administration of
boceprevir with ritonavir-boosted HIV protease inhibitors.
However, as described in another presentation at CROI, boceprevir combined with pegylated interferon and ribavirin appeared
safe and effective for HIV/HCV coinfected people taking boosted HIV protease
inhibitors. A small number of participants experienced HIV viral breakthrough
– which could be a consequence of reduced antiretroviral drug levels
this occurred in both the boceprevir arm (three of 64 patients) and the group
receiving pegylated interferon/ribavirin alone (four of 34 patients).
These conflicting results make it difficult to know
how to manage HIV/HCV-coinfected patients today. At a CROI symposium on this
topic Jürgen Rockstroh from University
of Bonn said, "For
now the only recommendation we can give is that patients not newly start
boceprevir-based therapy with any of the listed HIV protease inhibitors."
However, Douglas Dieterich from Mt Sinai Medical Center suggested in an
interview that "it's perfectly appropriate to use either
boceprevir or telaprevir as long as you're cognisant of drug-drug
interactions" and frequently monitor both HIV and HCV viral load.
Another option, favoured by both Rockstroh and
Dieterich, would be to use boceprevir with the HIV integrase inhibitor
In another poster at CROI, Clara de Kanter and
colleagues from University of Nijmegen in the Netherlands reported findings from
a drug-drug interaction study of 24 healthy volunteers who either received 800mg three-times-daily boceprevir for ten days then added
400mg raltegravir once-daily, or else took the same drugs in the reverse order.
No interactions were expected based on how the drugs are
processed in the body and concentrations of raltegravir fell within normal range,
leading the researchers to conclude that boceprevir has "no clinically
meaningful effect" on raltegravir pharmacokinetics.
to the absence of a clinically significant drug interaction," they
continued, "raltegravir can be recommended for combined HIV/HCV treatment