Treatment Effective for HIV+ Men with Acute HCV
Acute hepatitis C treatment with pegylated interferon plus
ribavirin was highly effective for HIV positive gay and
bisexual men, even with a shorter 24-week duration of therapy.
around 2000 clinicians in large European cities began to report
outbreaks of apparently sexually transmitted acute hepatitis
C virus (HCV) among HIV positive
men who have sex with men (MSM). Similar cases have since been
seen in Australia and the U.S.
of HCV monoinfected people have
shown that treatment during the acute stage of infection is
very effective, resulting in higher sustained virological response
(SVR) rates than later treatment during chronic infection.
HCV infection is often asymptomatic, however, and is usually
not detected during this early period in HIV negative individuals.
But HIV positive people taking antiretroviral
therapy (ART) typically receive regular liver function monitoring,
which can reveal liver enzyme elevations indicative of new HCV
described in the June
19, 2011, issue of AIDS, Femke Lambers and fellow
investigators with the Dutch MOSAIC (MSM Observational Study
of Acute Infection with Hepatitis C) study group evaluated the
efficacy of treatment and the effect of duration of therapy
in HIV positive men with acute hepatitis C.
For HCV monoinfected people, the standard duration of therapy
for chronic hepatitis C is 24 weeks for those with genotypes
2 or 3, and 48 weeks for those with difficult-to-treat genotypes
1 or 4; 24 weeks is usually considered sufficient for acute
infection regardless of genotype. For HIV positive people, however,
many experts recommend the longer 48-week course for all genotypes,
for both acute and chronic infection.
The present analysis included 50 HIV positive MSM at 2 hospitals
in Amsterdam. All had acute HCV infection, defined as less than
2 years between the last negative HCV antibody or RNA test and
the first positive test, and less than 2 years between the estimated
time of infection (midpoint between the last negative and first
positive test) and the start of treatment; 2 additional men
met the inclusion criteria but spontaneously cleared HCV and
were excluded from further analysis.
The participants' median age was 42 years. Most (68%) had HCV
genotype 1, 26% had genotype 4, and just 6% had genotypes 2
or 3. About two-thirds were on antiretroviral therapy for HIV
and the average CD4 cell count was high (about one-third each
with < 380, 380-550, and > 550 cells/mm3).
All participants were treated with 180 mcg/week pegylated interferon
alfa-2a (Pegasys) plus daily weight-adjusted ribavirin. The
21 patients (42%) at one hospital were to be treated for 24
weeks, while the 29 patients (58%) at the other were to be treated
for 48 weeks. In actuality, not everyone was treated for the
planned duration, with the shorter-duration group ranging from
22 to 36 weeks (median 24) and the longer-duration group ranging
from 47 to 58 weeks (median 48).
patients (6%) stopped treatment around week 12 due to non-response.
3 (6%) stopped prematurely due to side effects.
patients with available data at 4 weeks, 54% achieved rapid
virological response (RVR).
those with available data at 12 weeks, 87% achieved early
virological response (EVR).
patients (88%) had undetectable HCV RNA at the end of treatment.
38 people (76%) achieved SVR, or continued undetectable
HCV RNA after completion of treatment.
and EVR were both highly predictive of SVR:
predictive values were 95% and 85%, respectively;
predictive values were 44% and 100%, respectively.
likelihood of SVR was higher with longer duration of therapy,
but the difference did not reach statistical significance:
a univariate analysis, SVR was not significantly associated
with treatment duration overall (odds ratio 1.53 for
48 vs 24 weeks).
a multivariate analysis adjusting for genotype and
other factors, the effect of treatment duration was
larger but still not significant (adjusted odds ratio
patients without RVR, 40% of those treated for 24
weeks and 64% treated for 48 weeks achieved SVR, but
the numbers were small and the difference again did
not reach statistical significance.
high SVR rate of 76% in this study confirms that treatment of
HCV infection can be successful in HIV-infected patients when
started in the acute phase and should encourage clinicians to
treat this complicated patient group," the study authors
"Although the adjusted odds of attaining SVR was 2.2 times
higher for 48 weeks of treatment compared with 24 weeks, this
difference was not statistically significant," they continued.
"This suggests that 24 weeks of treatment might be sufficient.
This result strengthens the evidence for recommendations in
current treatment guidelines for acute HCV infection in HIV
coinfected patients. The shorter regimen would be of great advantage
for patients, as both peginterferon and ribavirin can cause
serious side effects."
Since this study was done, the advent of direct-acting antiviral
agents has increased treatment response rates for people with
chronic hepatitis C, when used in combination with pegyalted
interferon/ribavirin. These new drugs have not yet been extensively
studied for acute infection, but could potentially lead to higher
response rates than current standard therapy alone.
affiliations: Department of Research, Public Health Service
of Amsterdam, Cluster of Infectious Diseases, Netherlands; Department
of Internal Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam,
Netherlands; Section of Clinical Virology, Department of Medical
Microbiology, Academic Medical Center, Amsterdam, Netherlands;
Department of Medical Microbiology, Onze Lieve Vrouwe Gasthuis,
Amsterdam, Netherlands; National Institute of Public Health
and the Environment, Bilthoven, Netherlands; Division of Infectious
Diseases, Tropical Medicine and AIDS (CINIMA), Department of
Internal Medicine, Academic Medical Center, Amsterdam, Netherlands.
Lambers, K Brinkman, J Schinkel, et al. for MOSAIC (MSM Observational
Study of Acute Infection with hepatitis C) study group. Treatment
of acute hepatitis C virus infection in HIV-infected MSM: the
effect of treatment duration. AIDS 25(10):1333-1336 (abstract).
June 19, 2011.