Reuters Health Information (2012-07-30): High-dose ribavirin plus EPO no extra help against HCV in HIV
Drug & Device Development
High-dose ribavirin plus EPO no extra help against HCV in HIV
Last Updated: 2012-07-30 14:00:14 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Intensified ribavirin dosing given along with erythropoietin (EPO) does not improve virologic response in patients with chronic hepatitis C virus and coexisting HIV infection, Spanish researchers have found.
The effect of ribavirin on sustained virologic response that was seen in many prior studies was not seen in the PERICO trial, co-investigator Dr. Pablo Barreiro told Reuters Health. "Nor was (there) a benefit of greater RBV doses," he added.
Dr. Barreiro, of Hospital Carlos III, Madrid, and colleagues point out in their paper in the Journal of Infectious Diseases online July 17 that the combination of peginterferon-alpha and ribavirin for treating chronic hepatitis C leads to cures in 25%-50% of HCV/HIV-coinfected patients.
Higher ribavirin exposure can improve this rate, but anemia often limits that strategy, prompting the PERICO researchers to explore the preemptive use of erythropoietin while doubling the first few doses of ribavirin.
They randomly assigned 357 patients with HCV and HIV infection who were naive to interferon to receive peginterferon-alpha-2a and either standard ribavirin (1,000 or 1,200 mg/day depending on weight) or ribavirin induction at 2,000 mg/day along with subcutaneous erythropoietin during the first four weeks. Thereafter, standard ribavirin was given until completion of therapy.
A total of 251 patients completed the planned course of treatment, and 160 attained a sustained virologic response. On an intention-to-treat basis, the SVR rate was 43% in the induction arm and 47% in the standard arm (p=0.4), the investigators found.
"Unexpectedly, mean ribavirin trough concentration at week four was comparable in both treatment arms," they report. Erythropoietin (EPO) may be the reason for this and for the lack of difference in virologic response, Dr. Barreiro explained in his emailed comments.
"Use of EPO may have blunted (the) ribavirin effect, as red cells sequester free-active ribavirin," he said. "Practical lessons may be that the association between anemia and SVR could be related to greater ribavirin exposure. Therefore EPO should be used with caution, particularly in the first weeks of hepatitis C therapy."
He and his colleagues conclude: "While awaiting ... the arrival of new direct-acting antivirals against HCV, it seems worth to ensure maximal ribavirin exposure when treating HIV/HCV-coinfected patients, limiting the indication of erythropoietin only to patients that develop severe anemia on therapy."
Asked for his take on the study, Dr. Amalio Telenti told Reuters Health, "It represents a valid, if minor addition to the field."
Dr. Telenti, Professor of Medical Virology at the University of Lausanne, Switzerland, has extensive experience of HCV coinfection in the Swiss HIV Cohort Study.
The current study, he explained in his emailed remarks, "includes both viral genotypes 1/4 and 2/3 infected individuals. The majority are actually genotype 1, for whom the treatment paradigm has been profoundly changed by the recent availability of the HCV protease inhibitors."
Thus, he concluded, "The paper will have limited impact on that particular difficult-to-treat group of individuals."
J Infect Dis 2012.