AASLD 2012: Low viral load in hepatitis C treatment: Is a third drug necessary? – ELPA – European Liver Patients Association

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2012-11-26 08:50

When resources for hepatitis C treatment with new directly acting antivirals are limited, findings from the United States suggest that previously untreated patients with low viral load 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 HCV genotype 1 patients 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 genotype 1 patients 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 patients with low viral load. An abbreviated treatment course that does not include a directly ating 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 response.

The study recruited therapy-naïve patients 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 (800 mg 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) (SVR12).

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%).

HCV genotype 1b patients achieved higher SVR rates in 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 these patients with low viral load who achieve RVR success at 4 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.

Reference

Brian Pearlman et al. Hepatitis C virus (HCV) genotype 1 (G1) infection with low viral load (LVL) and rapid virologic response (RVR) to peginterferon and ribavirin (PEG/RBV) can be treated without a protease inhibitor (PI), irrespective of IL-28B status or patient ethnicity. Parallel session 22, Abstract 151. The 63rd Annual Meeting of the Amercian Association of the Study of Liver Diseases, Boston USA, 9-13 November 2012.

News also posted at: http://www.aidsmap.com/Low-viral-load-in-hepatitis-C-treatment-Is-a-third-drug-necessary/page/2553324/