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.
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.