Viral Decline during Hepatitis C Treatment in HIV/HCV Coinfected
People with Favorable IL28B Pattern
HIV/HCV coinfected patients with the C/C IL28B gene
pattern experience larger decreases in hepatitis C
virus (HCV) levels during the first phase of viral
decline after starting treatment with pegylated interferon
plus ribavirin, and were more likely to achieve virological
response, researchers reported in the December
19, 2010 advance online edition of the Journal
of Acquired Immune Deficiency Syndromes. A
similar effect was seen for second-phase viral decline
in people with HCV genotype 1, but not genotype 3.
is now well recognized that the pattern of genetic variations
on chromosome 19 near the IL28B gene, which controls production
of interferon lambda, is strongly
associated with outcomes in people with hepatitis C. A single
nucleotide polymorphism (SNP), or substitution of a single genetic
building block, known as rs12979860 has been implicated most
This SNP has 2 natural variations -- dubbed "C" and
"T" -- and each individual carries 2 copies, one from
each parent. People with the C/C pattern are more likely to
spontaneously clear HCV and respond better to interferon-based
therapy than those with the C/T or T/T patterns. This association
is strong in people with HCV alone. It has also been demonstrated,
but may be weaker, in people with HIV/HCV coinfection.
In the present study, Evaldo Stanislau Affonso de Araoejo from
the University of Sao Paulo in Brazil and colleagues examined
the association between IL28B rs12979860 pattern and HCV kinetics
(changes in virus levels) in this population during treatment
with pegylated interferon
analysis included 26 HIV/HCV coinfected patients from South
America who were treated with pegylated
interferon alfa-2a (Pegasys) and ribavirin. The researchers
measured serum HCV RNA and interferon concentrations frequently
during the first 12 weeks of therapy.
and white patients had a similar distribution of IL28B genetic
variations (P = 0.5), in contrast with prior research suggesting
that lower frequency of the favorable C/C pattern may help
explain why blacks respond less well to interferon.
C/C gene pattern was over-represented among people with
HCV genotype 3 compared with genotype 1 (P = 0.015).
patients with HCV genotype 1 and genotype 3, first-phase
viral decline immediately after starting therapy was larger
-- and interferon effectiveness was greater -- in individuals
with the C/C pattern compared with C/T or T/T.
genotype 1 patients, the slower second-phase viral decline
during days 2-29 was also larger, and infected cells were
lost at a greater rate, in those with the C/C pattern.
associations were not observed, however, in people with
HCV genotype 3.
virological response (week 2) and complete early virological
response (week 12) were significantly associated with the
C/C gene pattern.
of 11 patients with C/T or T/T patterns failed to achieve
sustained virological response (SVR), but the association
between the C/C pattern and SVR did not reach statistical
Overall, in HIV/HCV coinfected patients, the IL28B rs12979860
C/C gene pattern "was most strongly associated with a higher
first-phase viral decline and greater average [pegyalted interferon]
effectiveness during the first week of therapy," the study
authors concluded. "These findings indicate that [pegyalted
interferon] has greater efficacy in blocking HCV production/release
in patients with the favorable IL28B CC-genotype."
added that pharmacodynamic analysis showed that the IL28B C/C
pattern "conferred increased sensitivity to [pegyalted
interferon]," as shown by a lower EC50, or 50% effective
kinetic findings raise the possibility that the IL28B C/C genotype
favorably affects viral response by augmenting [interferon lambda]
mediated activation of the [interferon] signaling cascade, leading
to increased effectiveness in blocking virion production/release,"
they explained. "Notably, as we approach a new era of combination
therapy with [pegyalted interferon] and direct antiviral agents,
a better understanding of factors associated with [pegyalted
interferon]-related viral kinetics will provide the basis to
develop optimal treatment strategies for HCV."
affiliations: University of Sao Paulo Hospital das Clinicas,
Sao Paulo, Brazil; Department of Medicine, University of Illinois
at Chicago, Chicago, IL; Bar Ilan University, Life Sciences
Faculty, Ramat Gan, Israel.
Affonso de Araoejo, H Dahari, SJ Cotler, and others. Pharmacodynamics
of PEG-IFN alpha-2a and HCV response as a function of IL28B
polymorphism in HIV/HCV co-infected patients. Journal of
Acquired Immune Deficiency Syndromes (Abstract).
December 19, 2010 (Epub ahead of print).