 Liver
Fibrosis Progression in HIV-HCV Coinfected Patients Treated with Interferon plus
Ribavirin
By
Liz Highleyman
Prior
research has shown that HIV-HCV coinfected patients tend to experience more rapid
liver fibrosis progression than HIV negative individuals with chronic hepatitis
C, though some data suggest that this is mainly a concern for people with advanced
HIV disease and low CD4 cell counts. In
the present study, reported in the March 1, 2008 issue of Clinical Infectious
Diseases, Firouze Bani-Sadr and colleagues assessed the prevalence of and
risk factors for progression of fibrosis in the French RIBAVIC study.
This
trial included about 400 HIV-HCV coinfected patients who were randomly assigned
to receive 1.5 mcg/kg once-weekly pegylated interferon alpha-2b (PegIntron) or
3 MU thrice-weekly conventional interferon alpha-2b, both with 800 mg daily ribavirin,
for 48 weeks.
As
previously reported, 27% of patients in the pegylated interferon arm achieved
sustained virological response (SVR) - somewhat lower than the rates of 40% in
the APRICOT trial and 44% in ACTG 5071, 2 other studies using similar regimens
conducted around the same time. It has since been demonstrated that higher weight-based
dosing of ribavirin produces better outcomes.
The present analysis included
383 coinfected patients who received at least 1 dose of study therapy, of whom
198 had interpretable paired pre- and post-treatment liver biopsy specimens (mean
interval between biopsies 109 weeks). Histological worsening of fibrosis was defined
as an increase of 2 or more points in patients with initial stage 4 or lower fibrosis,
or an increase of 1 point in those with initial stage 5.
 Results
•
Fibrosis worsened in 34 patients (17.1%).
•
In univariate analyses, worsening fibrosis was significantly associated with the
following factors; •
In
a multivariate analysis, lack of SVR (OR 9.05; P = .003) and use of ddI (OR 3.34;
P = .007) remained significantly associated with worsening fibrosis.
Conclusion
Based
on these findings, the authors hypothesized that, "The mitochondrial toxicity
of antiretrovirals, such as didanosine, seems to play a major role in worsening
of fibrosis during HCV therapy."
Therefore, they recommended, "anti-HCV
therapy should ideally be administered before antiretroviral treatment initiation.
If anti-HCV and anti-HIV treatments have to be administered concomitantly, then
nucleoside reverse transcriptase inhibitors with the lowest mitochondrial toxicity
should be preferred."
Current
international HIV-HCV coinfection treatment guidelines recommend that ddI
"should never be used" in combination with ribavirin due to the additive
risk of mitochondrial toxicity.
3/11/08
Reference
F Bani-Sadr,
N Lapidu, P Bedossa, and others (Viral Hepatitis-HC02-Ribavic Study Team). Progression
of fibrosis in HIV and hepatitis C virus-coinfected patients treated with interferon
plus ribavirin-based therapy: analysis of risk factors. Clinical Infectious
Diseases 46(5): 768-774. March 1, 2008. |
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