Prolonging hepatitis C therapy by an additional 20 weeks has few benefits

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Prolonging the duration of hepatitis C therapy in HIV-positive patients chronically coinfected with hepatitis C virus only has a long-term benefit for individuals infected with the easier-to-treat genotypes of hepatitis C, according to data presented to the Third International Workshop on HIV and Hepatitis Coinfection held in Paris last week.

HIV-positive individuals chronically coinfected with hepatitis C virus typically have a poor response to anti-hepatitis C therapy. Of the third or so of patients who do achieve a sustained virological response (an undetectable hepatitis C viral load six months after hepatitis C therapy has been completed) many experience a subsequent relapse of their hepatitis C infection. Some doctors have suggested that prolonging anti-hepatitis C therapy by up to six months may increase the chances of coinfected patients achieving a sustained response to their therapy.

Italian investigators therefore designed the ROMANCE study involving coinfected patients. All achieved an end of treatment response to hepatitis C therapy consisting of pegylated-interferon and doses of ribavirin adjusted by weight. The standard duration of treatment was initially provided: patients infected with the easier-to-treat hepatitis C genotypes 2 and 3 received 24 weeks of hepatitis C therapy, and those with genotypes 1 and 4, which are harder-to-treat, received 48 weeks treatment.

Glossary

odds ratio (OR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 

adjusted odds ratio (AOR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 

on treatment analysis

Participants in a clinical trial are only included in the final analysis if they complete the full course of treatment they were originally assigned to. 

statistical significance

Statistical tests are used to judge whether the results of a study could be due to chance and would not be confirmed if the study was repeated. If result is probably not due to chance, the results are ‘statistically significant’. 

intent to treat analysis

All participants in a clinical trial are included in the final analysis, in the groups they were originally assigned to, whether or not they actually completed their course of treatment. This method provides a better estimate of the real-world effect of a treatment than an ‘on treatment’ analysis.

Patients were then randomised to either stop therapy (Arm A) or to receive an additional 20 weeks of anti-hepatitis C treatment (Arm B). The investigators then compared the proportion of patients who achieved a sustained virological response.

The study enrolled 123 patients between 2002 and 2004. Most of the patients (77%) were men, and 41% had advanced fibrosis.

Over a third (21 patients, 38%) of patients who received prolonged duration of therapy stopped treatment early, either because of side-effects or because they dropped out of the study.

Intent-to-treat analysis showed that continuing treatment conferred no additional benefit. There was no difference in the proportion of patients between Arm A and Arm B (60% versus 60%) who achieved a sustained virological response. As expected, significantly more patients with

genotypes 2 and 3 achieved a sustained treatment response than those with genotypes 1 and 4 (80% versus 64%).

The investigators then performed an on-treatment analysis which was restricted to the patients who completed treatment. This showed that 90% of patients with genotypes 2 and 3 achieved a sustained virological response compared to 60% of those with genotypes 1 and 4, a statistically significant difference (p = 0.04).

Factors significantly associated with an improved odds of a sustained virological response for patients with genotypes 2 and 3 were a higher hepatitis C viral load at baseline (above 600, 000 copies/ml, adjusted odds ratio, 0.15), and a rapid response to anti-hepatitis C therapy (undetectable viral load after four weeks, adjusted odds ratio, 1.08).

The investigators concluded that providing an additional 20 weeks of anti-hepatitis C therapy did not increase the chances of HIV-positive patients coinfected with hepatitis C virus genotypes 1 and 4 achieving a sustained virological response. Continuing treatment for an additional 20 weeks was beneficial for patients with genotypes 2 and 3, provided that they had a higher hepatitis C viral load at baseline, and an undetectable hepatitis C viral load after four weeks of treatment.

References

Puoti M et al. Results of randomised controlled trial on the impact of prolonged combination anti HCV treatment on relapse rate in HIV/HCV coinfected patients with HCV RNA negativization at the end of 24 - 48 weeks course of treatment: The ROMANCE study. Third International Workshop on HIV and Hepatitis Coinfection, abstract 1, Paris, 2007.