Cochrane Review of Pegylated Interferon plus Ribavirin for Hepatitis C Treatment in People with HIV

Pegylated interferon (Pegasys or PegIntron) plus ribavirin is an appropriate standard of care for HIV-HCV coinfected patients, with sustained virological response rates of 26% for hepatitis C virus (HCV) genotypes 1 or 4 and 57% for genotyes 2 or 3, according to a meta-analysis by the Cochrane Hepato-Biliary Group published in the September 2009 American Journal of Gastroenterology.

By Liz Highleyman

Pegylated interferon plus ribavirin is considered standard therapy for hepatitis C for both HIV negative and HIV positive individuals, but studies of coinfected patients have produced inconsistent response rates.

Lise Lotte Gluud and colleagues with the Cochrane Hepato-Biliary Group performed an analysis of trials to assess the efficacy of this regimen in coinfected individuals. The Cochrane Collaboration is an independent, non-profit network of experts that produces and disseminates systematic reviews of healthcare interventions and promotes evidence-based medicine.

Through manual and electronic searches, the authors identified randomized clinical trials comparing pegylated interferon plus ribavirin versus other antiviral treatments for HIV positive patients with chronic hepatitis C.

The primary outcome measure was virological response at the end of treatment (EOT) and sustained virological response (SVR) measured 6 months after completion of therapy. The investigators performed intention-to-treat meta-analyses using data from all randomized patients.

Results

	The researchers found 7 randomized trials that were eligible for inclusion.
	The included patients had stable HIV disease, chronic hepatitis C, and were treatment-naive, having not previously been treated with interferon or ribavirin.
	Mean dosages used were 180 mcg/week for pegylated interferon alfa-2a (Pegasys) or 1.5 mcg/kg/week for pegylated interferon alfa-2b (PegIntron) -- the standard of care for both HIV negative and HIV positive patients.
	The mean dose of ribavirin was 800 mg/day, which is now considered low (standard is 1000-12000 mg/day adjusted according to body weight).
	Treatment duration ranged from 24 to 48 weeks (for HIV negative people, standard duration is 24 weeks for genotypes 2 or 3 and 48 weeks for genotypes 1 or 4, but many experts recommend 48 weeks for all HIV positive patients regardless of genotype).
	Pegylated interferon plus ribavirin increased the proportion of patients who achieved end-of-treatment or sustained virological response compared with conventional interferon plus ribavirin or pegylated interferon monotherapy.
	In subgroup analyses of trials comparing pegylated interferon plus ribavirin versus conventional interferon plus ribavirin, the proportion of patients achieving SVR was 26% for genotypes 1 or 4 and 57% for genotypes 2 or 3 (compared with rates of about 70%-80% and 50%, respectively, for HIV monoinfected people).
	Several adverse events occurred, including fatal lactic acidosis and liver failure.
	However, there were no significant differences in mortality rates between treatment groups.

Based on these findings, the study authors concluded, "Peginterferon plus ribavirin may be considered for treatment-naive patients with HIV and chronic hepatitis C. Adverse events should be monitored carefully."

Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark; Department of Internal Medicine, Gentofte University Hospital, Hellerup, Denmark; Section of Internal and Vascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy.

10/27/09

Reference
L Gluud, E Marchesini, and A Iorio. Lise Lotte Gluud. Peginterferon Plus Ribavirin for Chronic Hepatitis C in Patients With Human Immunodeficiency Virus. American Journal of Gastroenterology 104(9): 2335-2341. (Abstract).