September 29, 2012

High-dose ribavirin induction shows no benefit in HIV/HCV coinfection

Labarga P. J Infect Dis. 2012;206:961-968.

September 24, 2012

Researchers from Spain have found that high ribavirin induction did not improve sustained virological response rates among patients with HIV and hepatitis C virus coinfection.

The Peginterferon Ribavirin in Coinfection (PERICO) trial was a randomized prospective trial of the safety and efficacy of peginterferon alpha-2a with two different doses of ribavirin in coinfected patients. Patients received the standard dose or ribavirin according to weight, or a high fixed dose of 2,000 mg/day during the first 4 weeks of therapy. Those who received the high dose also received erythropoietin beta.

“Whereas the use of higher dosing of peginterferon alpha has not shown any benefit in terms of treatment success, the use of higher ribavirin exposure has led to improvements in the rate of HCV clearance, although the development of anemia is a major limitation of this approach,” the researchers wrote.

The study included 357 patients, of whom 160 attained a sustained virological response. There were no differences found in the rate of sustained virological response between the two groups. The level of undetectable HCV RNA and the mean ribavirin trough concentration were similar in both groups at week 4.

Ninety-one patients discontinued treatment due to nonresponse and 29 discontinued due to adverse effects. HCV genotypes 2 and 3, IL28B CC variants, nonadvanced liver fibrosis and rapid virological response were predictors of sustained virological response.

“The use of preemptive erythropoietin may have blunted the increased disposition of free ribavirin by promoting erythrocyte sequestration,” the researchers wrote. “While awaiting the arrival of new direct acting antivirals against HCV, it seems worthwhile to ensure maximal ribavirin exposure when treating HIV/HCV-coinfected patients, limiting the indication of erythropoietin only to patients who develop severe anemia on therapy.”

Disclosure: The researchers report no relevant financial disclosures.


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