The presence of a genetic variation in the IL28B gene is associated with better
response rates to hepatitis C therapy in patients who are co-infected with HIV
and hepatitis C, Spanish investigators report in the online edition of AIDS.
However, the beneficial effect of the variation in the IL28B gene was
restricted to patients who were infected with hepatitis C gentoypes 1 and 4,
which are generally harder to treat.
Separate research conducted at the same hospital showed that
the genetic variation, or polymorphism, also affected response rates in co-infected patients being re-treated
with anti-hepatitis C drugs.
An inherited gene which all individuals have. There are three genotypes of IL28B; these influence response to hepatitis C and its treatment. People with CC genotype are more likely to spontaneously clear acute infection or (during chronic infection) respond well to interferon-based treatment. The other two genotypes are known as CT and TT.
- rapid virological response (RVR)
An undetectable hepatitis C RNA viral load within 4 weeks of starting treatment. An extended rapid virological response (eRVR) is when viral load is undetectable within 4 weeks and remains undetectable until at least week 12.
- sustained virological response (SVR)
Undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 24 weeks (six months) after ending treatment and is considered to be a cure. SVR4 and SVR12 refer to RNA remaining undetectable for 4 and 12 weeks respectively.
The researchers believe that their findings will help to guide
decisions about hepatitis C therapy.
HIV and hepatitis C have shared modes of transmission and in some regions of the wrold a
large proportion of HIV-positive patients are co-infected with hepatitis C.
Liver disease caused by hepatitis C is a leading cause of serious illness and
death in co-infected patients.
Standard therapy for hepatitis C consists of pegylated
interferon and ribavirin. It can cause unpleasant side-effects and only a
minority of HIV-positive patients with chronic hepatitis C successfully respond
to this treatment.
In hepatitis C mono-infected patients, the IL28B genetic variation has
been associated with better treatment outcomes. Several studies in HIV/HCV co-infected patients have also shown that the IL28B polymorphism predicts treatment response.
Investigators from the Carlos III Hospital in Madrid wished
to see if the genetic variant also influenced therapeutic responses in co-infected
They therefore tested stored blood samples obtained from 196
co-infected people who had completed hepatitis C therapy and analysed the
response rates of their patients.
All the patients were of European origin, 75% were men
and their average age was 42.
Median CD4 cell count was 483 cells/mm3, and
three-quarters of patients treated with anti-HIV drugs had an undetectable
Over two-thirds (69%) of patients were infected with the
harder to treat hepatitis C genotypes. However, 70% of patients had only mild
Analysis of frozen blood samples showed that 44% of patients
carried the IL28B genetic variation.
Overall, 54% of patients had a successful response to
treatment – an undetectable hepatitis C viral load six months after the completion
of therapy, or sustained virological response (SVR).
A rapid virological response (RVR) – an undetectable
hepatitis C viral load after four weeks of treatment – was observed in 21% of
patients. An early virological response (EVR, 2 log drop in viral load at week
12) was achieved by 80% of patients, and 59% had undetectable hepatitis C at
this time (complete early virological response, or cEVR). On the completion of
therapy (EOTR), 65% of patients had an undetectable hepatitis C viral load.
Patients carrying the IL28B polymorphism had higher treatment
response rates at all time intervals than those who did not have this gene.
RVR = 51 vs 17%, p < 0.0001.
EVR = 100 vs 62%, p < 0.0001.
cEVR = 82 vs 41%, p < 0.0001.
EOTR = 87 vs 48%, p < 0.0001.
SVR = 76 vs 36&, p < 0.0001.
However, higher treatment response rates were only seen in
patients with the IL28B polymorphism who were infected with hepatitis C genotypes 1 and
4 (p < 0.0001 at all time points). Treatment outcomes rates for patients
with genotypes 2 and 3 were comparable regardless of carriage of the gene.
The beneficial effect of the IL28B gene for patients with
genotypes 1 and 4 appeared to be associated with early responses to therapy.
Patients carrying the gene had significantly greater
declines in hepatitis C viral load at weeks 4 and 12 than individuals who did
not (both p < 0.0001).
Nevertheless, presence of the IL28B polymorphism was associated with
higher sustained treatment response rates even in patients who did not achieve
an early response to therapy (64 vs 27%, p = 0.001).
“Our results suggest that although the effect of the IL28B
polymorphism on SVR is largely mediated by its impact on early viral responses
on treatment, as RVR and EVR they exert its action beyond that, influencing the
SVR regardless of the achievement of RVR,” write the authors.
They conclude, “our study demonstrates an important role for
IL28B genotypes in predicting on-treatment virological responses to therapy in
HIV/HCV-coinfected individuals…knowledge at baseline of the IL28B genotype may
helpfully assist in treatment decisions.”