Interim results presented at the Infectious Diseases Society of America (IDSA) conference yesterday show that 70.5% of 98 patients with HIV and hepatitis C who took the hepatitis C protease inhibitor (PI) drug boceprevir (Victrelis), plus pegylated interferon and ribavirin (pIFN/RBV) had an undetectable hepatitis C viral load by week 24 of the 48-week placebo-controlled study. This compares with 34.4% on placebo.
These results compare with a 68% response rate seen for the other licensed hepatitis C PI telaprevir (Incivo in the EU or Incivek in the US) in co-infected patients, which were presented at the Conference on Retroviruses and Opportunistic Infections (CROI) this February. In the case of telaprevir, these results were at week twelve of a 48-week study.
One difference in results between the two drugs was that only 5% of patients receiving placebo in the telaprevir study had an undetectable viral load at week 12.
There were two other differences. Firstly, in the boceprevir study every patient was on antiretroviral therapy (ART) for HIV and had an HIV viral load of under 50 copies/ml, while in the telaprevir study 22% of patients were not on ART (but responded equally well to telaprevir). Secondly, in the telaprevir study patients on ART took either the NNRTI drug efavirenz or the HIV PI drug boosted atazanavir, while in the boceprevir study any PI was allowed but no NNRTIs. The nucleoside (NRTI) drugs AZT, d4T or ddI were also excluded.
Two things are important to emphasise. First, in both cases these are interim results and do not show what proportion of patients achieved a sustained viral response (SVR), indicating complete clearance of hepatitis C from the body, at the study’s end. In the studies of mono-infected patients, both drugs achieved an SVR in about 80% of patients but given that a proportion of patients who achieve undetectable viral loads on hepatitis C treatment relapse after it is stopped, SVR rates are likely to be lower in co-infected patients.
Secondly, the patient group in both studies were those patients most likely to respond. They were all treatment-naive for hepatitis C treatment (had not taken treatment before) and had genotype 1 of hepatitis C. Boceprevir and telaprevir are both currently licensed only for treatment of hepatitis C genotype 1 in Europe and the USA; genotype 1 is the most common hepatitis C genotype and one of the hardest to treat, but these PIs have little activity against some of the other genotypes.
In terms of side-effects, those more common with boceprevir rather than placebo were neutropenia (low white blood cells – 13% versus 3%), bad taste (25% versus 15%), vomiting (25% versus 15%), fever (34% vs 21%) headache (28% versus 12%) and poor appetite (28% versus 12%). Study discontinuations for clinical adverse events occurred in 14% of patients on boceprevir and 9% on placebo. However clinical adverse events classed as ‘serious’ occurred in 8% of patients on boceprevir and 21% on placebo. In telaprevir studies, the most notable side-effect has been rash, classed as ‘severe’ in 7% and 15% of mono-infected patients in the two licensing studies of telaprevir.
The treatment regimen used in the study was 800mg of boceprevir three times a day. There was a four-week lead-in period on pIFN/RBV alone: the idea of this is to reduce the initial size of the HCV viral load sufficiently to avoid the generation of resistance to boceprevir.
Full results from the study are expected next year.
Sulkowski M et al. Boceprevir plus peginterferon/ribavirin for the treatment of HCV/HIV co-infected patients: interim on-treatment results. 49th Annual Meeting of the Infectious Diseases Society of America, Boston, abstract LB-37, 2011. See http://idsa.confex.com/idsa/2011/webprogram/Paper33020.html