Hepatitis C treatment responses in patients
co-infected with HIV are better in patients infected with hepatitis C subtype-1b than 1a, according to Spanish research published in the online edition of the Journal of Acquired Immune Deficiency
Syndromes. The research also showed that the presence of the IL28B gene
influenced treatment responses.
“We noticed that on treatment responses and
SVR [sustained virological response] rates were uniformly worse in HCV-1a as
compared to HCV-1b patients,” comment the authors. “Another important finding
of our study was that early viral kinetics in HCV-1 patients was significantly
HIV and hepatitis C share modes of
transmission, and liver disease caused by hepatitis C is now an important cause
of death in co-infected patients.
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.
Standard therapy for hepatitis C consists
of pegylated interferon and ribavirin. Only a minority of co-infected patients
with chronic hepatitis C infection have a successful response to this therapy.
However, several factors are known to be associated with treatment with
One of these is hepatitis C genotype.
Poorer responses are seen in patients infected with genotypes 1 and 4 compared
to genotypes 2 and 3. In addition, it is possible that viral subtype may also have
an impact on outcomes.
Studies conducted in both hepatitis
C-mono-infected patients and co-infected individuals have also shown that the
IL28B gene also influences treatment responses.
Two protease inhibitors were recently
approved for the treatment of hepatitis C mono-infection. These drugs works
directly against hepatitis C and other such directly acting agents are in
development. However, these new protease inhibitors are combined with the
existing standard therapy, so an understanding of the importance of viral
subtype and genetics to treatment outcomes remains important.
Therefore Spanish investigators designed a
retrospective study involving 331 co-infected patients treated with pegylated
interferon and weight-based ribavirin. All had a CD4 cell count above 300
cells/mm3, were receiving their first course of hepatitis C therapy,
and none had decompensated liver disease or abused alcohol.
The patients’ were tested at baseline to
determine their hepatitis C genotype and subtype and to see if they carried the
Treatment responses were assessed at weeks
four and twelve, the end of therapy and then 24 weeks later.
There was a wide distribution of
geno/subtypes, with 29% of patients infected with genotype-1 subtype a, 19%
with genotype-1 subtype b, 37% with genotype-3 and 15% with genotype-4.
Patients infected with genotype 1 had
higher hepatitis C viral loads compared to patients infected with the other
genotypes (p = 0.02). Viral load also differed according to subtype, and was
slightly higher for patients with subtype 1a infection compared to those with
subtype 1b. However, similar proportions of patients with subtype 1a and 1b
infection carried the IL28B gene (33% vs. 24%).
Treatment responses at all time points
differed according to genotype and subtype.
As expected, response rates were better for
patients with genotype-3 infection compared to those with genotypes-1 and -4.
However, responses also differed between
subtypes-1a and -1b. Patients with subtype-1b were significantly more likely
than those with subtype-1a to have a response at week twelve (p = 0.009), the
end of treatment (p = 0.005) and to achieve a sustained virological response (p
Therapeutic response also differed
according to IL28B status.
Restricting analysis to patients with
genotype-1 infections showed that the lowest response was seen in individuals
with subtype-1a infection who did not carry the IL28B gene and the best
response in those with subtype-1b infection who carried this gene (p <
After controlling for potentially
confounding factors, the investigators confirmed that subtype-1b and carriage
of IL28B were associated with improved treatment responses.
“This is the first study demonstrating an
important role for both IL28B variant and HCV-1 subtype in predicting
on-treatment virological responses to pegylated interferon/ribavirin in
HIV/HCV-co-infected individuals,” comment the investigators. They explain:
“this effect is largely mediated by an enhancement in viral kinetics during the
first twelve weeks of therapy.”
The authors conclude: “Baseline IL28B
testing may helpfully assist treatment decisions
in the new era of triple combination therapy, including directly acting agents.”