This
picture shows the structure of the Human Immunodeficiency Virus(HIV).
This
picture shows the structure of the Hepatitis C Virus (HCV).
Several
outbreaks of acute hepatitis C have been reported in recent years, mostly among
HIV positive men who have sex with men
in large cities in Europe.
In
the general population, acute HCV infection
is seldom diagnosed, since it often has no symptoms. But newly acquired HCV is
more likely to be detected among people with
HIV who receive regular liver function tests to monitor for antiretroviral
drug toxicity; a sudden rise in liver enzymes is a potential sign of a recent
HCV infection.
In
the treatment of chronic hepatitis C, it has been shown that rapid
virological response (RVR) to interferon-based
therapy, or undetectable HCV RNA at week 4, is a good predictor of eventual
sustained virological response (SVR). Researchers with the Australian Trial in
Acute Hepatitis C conducted a study to determine whether this was also true in
the case of acute HCV infection in people with HIV.
At the time of the
report, 140 participants with acute HCV had enrolled in the ongoing trial. Of
these, 96 (69%) elected to undergo treatment, of whom 28 (29%) were HIV positive.
HCV monoinfected individuals received pegylated interferon alfa-2a (Pegasys) monotherapy,
while HIV-HCV coinfected patients
received Pegasys plus ribavirin,
all for 24 weeks.
The coinfected subjects were more likely than HCV monoinfected
patients to be male (100% vs 62%), to be older (41 vs 30 years), to have baseline
HCV RNA > 400, 000 IU/mL (51% vs 31%), and to have HCV
genotype 1 (61% vs 51%). About 45% in both groups experienced symptoms of
acute hepatitis C seroconversion.
Results
•
Among 80 subjects with week 4 results, 9 of 23 (39%) in the HIV-HCV coinfected
group and 28 of 57 (49%) in the HCV monoinfected group achieved RVR.
•
Lack of RVR was associated with baseline HCV RNA > 400,000 (58% for non-RVR
vs 19% for RVR patients), but not with estimated duration of HCV infection.
•
Patients with HCV genotype 1 were slightly more likely to fail to achieve RVR
(63% vs 41%), which was of borderline statistical significance.
•
The predictive value of RVR for SVR was assessed in 49 subjects with adequate
follow-up (15 coinfected, 34 HCV monoinfected).
•
100% of patients with RVR achieved SVR (n = 24), compared with 56% of those without
RVR (n = 25).
•
The positive and negative predictive values of RVR for SVR were 100% and 44%,
respectively.
•
Positive and negative predictive values were the same for HIV-HCV coinfected and
HCV monoinfected individuals.
"Acute
hepatitis C treated individuals with an RVR are highly likely to achieve a sustained
virologic response, irrespective of HIV status," the researchers concluded.
Strategies involving shorter therapy in these subjects may be possible."
They
added that, "Alternative therapeutic strategies should be explored for individuals
with baseline characteristics predictive of non-RVR or those with non-RVR on current
standard acute hepatitis C therapy." Study
2
In
the second study, British, French, and German researchers evaluated virological
outcomes in a cohort of 150 HIV positive men with acute HCV infection enrolled
between 2001 and 2006. Acute HCV infection was defined as a positive HCV RNA PCR
test or HCV antibody seroconversion within 12 months after a negative PCR or antibody
test. Most patients (97) were tested for HCV due to a rise in liver transaminase
(ALT or AST) levels.
The median participant age was 38 years and 60% had
HCV genotype 1. The main identified risk factors for HCV infection were unprotected
sexual intercourse and drug use; 16% reported concomitant syphilis. At the time
of acute HCV diagnosis, 70% were on HAART, 80% had HIV RNA < 400 copies/mL,
and the median CD4 count was 433 cells/mm3. The median HCV RNA level was 6 log10
copies/mL.
Overall, 111 patients started anti-HCV treatment, 14 with pegylated
interferon monotherapy and 97 with pegylated interferon plus ribavirin. Most (90%)
started hepatitis C treatment within 6 months after HCV infection (median 12 weeks).
The median duration of anti-HCV therapy was 25 weeks.
Results
•
Among the 101 patients with completed follow-up, 64% achieved SVR.
•
There was no significant difference in SVR rates by HCV genotype (63% for genotype
1, 67% for other genotypes).
•
CD4 cell count, HIV viral load, HCV viral load, ALT level, type of HAART, and
duration of anti-HCV treatment duration had no significant effect on likelihood
of SVR.
"An
overall high rate of sustained virological response was obtained in 64% of HIV
coinfected patients with acute HCV infection with early anti-HCV treatment using
pegylated interferon alone or with ribavirin," the investigators concluded.
"This response was similar among patients infected by genotype 1 and non-1
genotype of HCV and largely due to early commencement of therapy."
S
Dominguez, S Bhagani, M Vogel, and others. High Rate of Sustained Virological
Response to an Early Course of Anti-HCV Treatment for Acute HCV Hepatitis in HIV+
Patients. CROI 2008. Abstract 1072.
Treatment
of Acute Hepatitis C in HIV Positive Individuals 
Results
