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Predicting response to acute hepatitis C treatment in HIV/HCV co-infected people
Liz Highleyman, 2013-10-14 10:50:00
HIV/HCV co-infected people with higher HCV viral
load, lower CD4 cell counts, older age and unfavourable IL28B status may not
respond as well to interferon-based treatment for acute hepatitis C and may
benefit from adding a direct-acting antiviral agent, researchers reported at
the IDWeek 2013 meeting last week in San Francisco.
Up to 25% of people infected with hepatitis C
virus (HCV) clear it spontaneously without treatment, whilst the rest go on to
develop chronic hepatitis C lasting more than six months. Most people treated
with pegylated interferon and ribavirin during acute infection achieve
sustained virological response (SVR), considered a cure.
People with HIV/HCV co-infection are less
likely to clear HCV spontaneously and less likely to respond to treatment
during acute infection, making them more likely to develop chronic infection.
Leah Burke from Weill Cornell Medical Center, Daniel Fierer from Mt
Sinai School of Medicine and colleagues looked at factors that predict
treatment response amongst co-infected individuals treated during acute HCV
Clinicians do not want, unnecessarily, to treat
people who would have cleared HCV on their own, so therapy is typically
recommended if people have detectable HCV RNA 12 weeks after exposure. The
usual course of treatment for acute hepatitis C in HIV-negative people is
pegylated interferon/ribavirin for 24 weeks, but the European AIDS Treatment
Network recommends considering 48 weeks for co-infected people who do not
experience rapid virological response (RVR), or undetectable HCV at four weeks.
team has been following a cohort of HIV-positive gay men with presumed sexually
transmitted hepatitis C for several years, reporting that they appear to
experience rapid and aggressive liver disease progression.
this year's Conference on Retroviruses and Opportunistic Infections (CROI), Fierer reported that adding the
HCV protease inhibitor telaprevir (Incivo or Incivek) to pegylated
interferon/ribavirin shortens the duration of treatment for acute hepatitis C and
increases the likelihood of a cure for this group. But adding a direct-acting
antiviral increases cost, side-effects and the potential for drug interactions
with antiretrovirals, so it would be useful to predict which patients are most
likely to respond to interferon/ribavirin alone and who could use extra help.
This retrospective analysis
included 75 HIV-positive patients with acute HCV infection who were treated at
Weill Cornell or Mt Sinai in New York City between January 2004 and January
2013. Participants were identified through referral from primary care
and HIV physicians, city sexually transmitted disease and public health clinics
and community outreach in high-risk populations.
Acute HCV infection was
defined as having a first positive HCV antibody or HCV RNA test within the
previous six month after having a previous negative test, or symptoms of
acute infection such as jaundice or elevated alanine aminotransferase (ALT).
All but one of the participants were
men who have sex with men, 61% were white, 23% were Hispanic, 16% were black; the median age was 42 years; about one-third had a history of injecting drug
use. They had been HIV-positive for a median of seven years, had a median CD4
count of 551 cells/mm3, three-quarters were on antiretroviral
therapy (ART) and 63% had undetectable HIV viral load.
Most participants (92%) had HCV
genotype 1, the most difficult type to treat. A high proportion (41%) of those
tested had the favourable IL28B CC gene variant. Nearly half had high
pre-treatment HCV viral load (>1,000,000 IU/ml). All started treatment with
pegylated interferon and ribavirin.
The overall SVR rate at 12 or 24
weeks after finishing therapy was 71%. At four weeks, 45% of participants experienced
RVR, of whom 91% went on to achieve SVR; two patients relapsed and one did not
have follow-up data.
Amongst the 53% who did not
experience RVR, half nevertheless went on to achieve a cure. In addition, there
were eight non-responders, four people who had HCV rebound while still on
treatment, seven who experienced either relapse or reinfection and one with
Factors that significantly predicted
RVR in a multivariate analysis were pre-treatment HCV viral load <1,000,000
IU/ml (odds ratio [OR] 17.24, or 17-fold higher likelihood), peak pre-treatment
ALT >600 IU/ml (OR 5.69) and having a CD4 count greater than 500 cells/mm3
SVR, significant predictors in a multivariate analysis that controlled for
other factors were high baseline HCV viral load (OR 6.17) and being aged 40 or
older (OR 5.68). Achieving RVR was a strong predictor of SVR, with an
odds ratio of 13.50, or 13-fold higher likelihood.
Black race was a significant predictor
of RVR in a univariate analysis and was of borderline significance for
predicting SVR; being Hispanic was also
a significant predictor of SVR in a univariate analysis. The association
between race/ethnicity and treatment response has been shown to be primarily
attributable to differences in the IL28B gene, which plays a role in interferon
responsiveness. The favourable IL28B CC variant is less common amongst people
of African descent. The researchers explained that they used race/ethnicity in
their statistical analysis because data about IL28B – identified in 2009 – was
only available for a subset of participants.
"The majority of HIV-infected
patients respond favourably to treatment with [pegylated interferon] plus
ribavirin in the acute stage of HCV infection," the investigators
concluded. However, "there is a need for improved
identification and optimisation of therapy in those who are at high risk of
acute HCV treatment failure."
They recommended that clinicians consider adding
a direct-acting antiviral for patients with "poor prognostic
factors", including CD4 count below 500 cells/mm3, peak
pre-treatment ALT below 600 IU/mL, age greater than 40 years, baseline
pre-treatment HCV RNA >1,000,000 IU/mL or black race, or for anyone who does
not experience RVR.
adding telaprevir or boceprevir (Victrelis)
can substantially increase side-effects and risk of antiretroviral drug
interactions, next-generation direct-acting antivirals in the pipeline are
better tolerated and produce higher cure rates with a shorter course of
treatment. Interferon-free regimens are expected to be available within about