When resources for hepatitis C treatment with new directly acting
antivirals are limited, findings from the United States suggest that previously
untreated people with low viral loads may stand a good chance of achieving a
sustained virologic response without adding telaprevir or boceprevir to
pegylated interferon and ribavirin, researchers from Atlanta reported at the 63rd
annual meeting of the American Association for the Study of Liver Diseases in Boston this month.
Presenter Brian Pearlman told
the conference that people with hepatitic C genotype 1 with low viral loads, represent
about 20% of all genotype 1 infections and that an abbreviated 24-week course
of pegylated interferon plus ribavirin is recommended for those who achieve
an RVR (rapid virologic response, at 4 weeks), which is observed in up to
half of patients with low viral load.
While the current
standard-of-care for people with genotype 1 is pegylated interferon plus
ribavirin plus an oral protease inhibitor, no prospective trial has yet
evaluated whether the use of a protease inhibitor results in superior
virological outcomes in people with low viral loads. An abbreviated treatment course that does not include a directly acting antiviral may prove to be better tolerated, but may be less effective in achieving sustained virologic response. It is also unclear if
African American patients can benefit from this same treatment abbreviation strategy, mainly due to the lower frequency among
African-Americans of the IL-28B 'CC' host genotype that predicts interferon
The study recruited treatment-naive people with
viral loads of less than 600,000 IU/ml at two Atlanta clinics. Participants received four
weeks of pegylated interferon alfa-2b (1.5 mcg/kg/wk) plus weight-based
ribavirin (1-1.2 gm/day). If they achieved a rapid virological response at week
4, they were randomised 1:1 to receive
either 24 weeks of additional pegylated interferon plus ribavirin plus
boceprevir (800mg three times a day) (28 weeks total therapy) or a further
20 weeks of pegylated interferon plus ribavirin (24 weeks total therapy).
Patients were stratified by IL-28B host genotype. The primary endpoint was a
sustained virologic response (undetectable HCV RNA at 12 weeks post-therapy)
Of the 198 patients reported who
started treatment, 49% (n = 101) achieved undetectability at 4 weeks (RVR) and
were randomised to add boceprevir (n = 49) or not (n = 52).
There were no significant
differences in baseline characteristics between the groups. Participants were
in their mid-50s and, had a high BMI (28 vs 29). Almost two-thirds were male,
one-third had HCV genotype 1a and two-thirds had the IL-28B 'CC' host
genotype. Approximately 20% had advanced liver disease (F3/F4 fibrosis) and
one third were African-American.
Overall, SVR12 rates did
not differ significantly between the two arms (90% vs 89%), and nor did
relapse rates (4% triple therapy vs 6% pegylated interferon / ribavirin).
When stratified by IL-28B host genotype SVR12 rates were similar by treatment
allocation (96% in both CC groups; 77% in both non-CC groups). There was no
significant difference in treatment outcomes among the African-American
sub-set of the trial population (82% vs 84%).
People with hepatitis C genotype 1b achieved
higher SVR rates both arms (triple therapy genotype 1b 93%, 1a 84%; double
therapy genotype 1b 93%, 1a 85%). Dose reductions (33% in both arms) and
discontinuations were similar between arms.
This prospective, randomised trial shows that for
genotype 1 patients with low viral load (below 600,000 copies) who achieve a
rapid response with pegylated interferon plus ribavirin, the addition of
boceprevir does not result in a higher success rate, irrespective of IL-28B
genotype, viral subtype or African-American ethnicity.
Since people with low viral
load who achieve RVR success at four weeks comprise approximately 10% of all
genotype 1 infections, this treatment strategy of not using a protease
inhibitor could mean substantial cost savings. Dr Pearlman said that the Atlanta group planned
to evaluate the impact of raising the “low viral load” threshold to 800,000
copies to see if they can repeat these results in more people.
The present study is ongoing, and
results will need to be duplicated in larger, multicentre trials before this
strategy can be considered for wider adoption.