Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons.
BACKGROUND
Chronic hepatitis C virus (HCV) infection is a cause of major complications in persons who are also infected with the human immunodeficiency virus (HIV). However, the treatment of HCV infection in such persons has been associated with a high rate of intolerance and a low rate of response. We conducted a multicenter, randomized trial comparing peginterferon plus ribavirin with interferon plus ribavirin for the treatment of chronic hepatitis C in persons coinfected with HIV.


METHODS
A total of 66 subjects were randomly assigned to receive 180 microg of peginterferon alfa-2a weekly for 48 weeks, and 67 subjects were assigned to receive 6 million IU of interferon alfa-2a three times weekly for 12 weeks followed by 3 million IU three times weekly for 36 weeks. Both groups received ribavirin according to a dose-escalation schedule. At week 24, subjects who did not have a virologic response (those who had an HCV RNA level greater than or equal to 60 IU per milliliter) underwent liver biopsy, and medications were continued in subjects with either a virologic response or histologic improvement.


RESULTS
Treatment with peginterferon and ribavirin was associated with a significantly higher rate of sustained virologic response (an HCV RNA level of less than 60 IU per milliliter 24 weeks after completion of therapy) than was treatment with interferon and ribavirin (27 percent vs. 12 percent, P=0.03). In the group given peginterferon and ribavirin, only 14 percent of subjects with HCV genotype 1 infection had a sustained virologic response (7 of 51), as compared with 73 percent of subjects with an HCV genotype other than 1 (11 of 15, P<0.001). Histologic responses were observed in 35 percent of subjects with no virologic response who underwent liver biopsy.


CONCLUSIONS
In persons infected with HIV, the combination of peginterferon and ribavirin is superior to the combination of interferon and ribavirin in the treatment of chronic hepatitis C. These regimens may provide clinical benefit even in the absence of virologic clearance. The marked discrepancy in the rates of sustained virologic response between HCV genotypes indicates that strategies are needed to improve the outcome in persons infected with HCV genotype 1.
Massachusetts General Hospital, Boston, MA 02114, USA. rtchung@partners.org
Raymond T
RT
Chung
Janet
J
Andersen
Paul
P
Volberding
Gregory K
GK
Robbins
Tun
T
Liu
Kenneth E
KE
Sherman
Marion G
MG
Peters
Margaret J
MJ
Koziel
Atul K
AK
Bhan
Beverly
B
Alston
Dodi
D
Colquhoun
Tom
T
Nevin
George
G
Harb
Charles
C
van der Horst
D000328:Adult; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D018937:Hepatitis C Antibodies / Q000097:blood; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*
D000998:Antiviral Agents; D018937:Hepatitis C Antibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a