By
Liz Highleyman
Gail
Matthews and fellow investigators with the Australian Trial
in Acute HCV (ATAHC) Study Group prospectively evaluated treatment
outcomes among people with acute (first 6 months after infection)
and early chronic hepatitis C
virus (HCV) infection.
Most studies indicate that people treated during the acute stage
of hepatitis C have a high SVR rate, but the likelihood of sustained
response has been shown to be lower among injection drug users,
HIV/HCV coinfected
patients, and people who start therapy later.
Acute hepatitis C is often treated for a shorter duration than
chronic infection (e.g., 24 weeks regardless of HCV
genotype) and may use pegylated interferon monotherapy without
ribavirin. However the optimal regimen for these more challenging
groups of patients remains unclear.
The present analysis included more than 100 participants with
acute or early chronic HCV infection. Three-quarters had a history
of injection drug use and 35% were HIV positive. HIV negative
participants were treated with pegylated
interferon alfa-2a (Pegasys) for 24 weeks, while those with
HIV/HCV coinfection received pegylated interferon plus ribavirin
for the same duration.
RNA decline was assessed among adherent participants who took
at least > 80% of prescribed doses of pegylated interferon.
Results
 |
In
an oral presentation, the researchers reported that among
89 adherent participants, HIV negative and HIV/HCV coinfected
patients had statistically similar average baseline HCV
viral load levels (5.04 vs 5.33 log IU/mL) and similar mean
declines in HCV RNA through week 4 (2.48 vs 2.94 log). |
|
50%
of HIV negative participants and 41% of coinfected patients
achieved complete RVR (defined as HCV RNA < 10 IU/mL
at week 4), again statistically similar. |
|
However,
mean reductions in HCV RNA were significantly greater among
the HIV/HCV coinfected patients compared with the HIV negative
patients at week 4 (3.91 vs 3.11 log) and week 12 (3.95
vs 3.10 log). |
|
Among
the adherent population, 72% of HIV negative participants
and 74% of HIV/HCV coinfected individuals achieved SVR (defined
as continued undetectable HCV RNA 24 weeks after completing
therapy). |
|
In
a poster presentation, the investigators reported that complete
RVR was the best predictor of SVR, with a positive predictive
value of 92% in adherent patients regardless of HIV status. |
|
The
positive predictive values of partial RVR (defined as HCV
RNA < 630 IU/mL at week 4) and complete early virological
response (defined as HCV RNA < 10 IU/mL week 12) were
similar for HIV negative and coinfected patients (84% vs
88% for partial RVR; 86% vs 82% for complete EVR). |
|
The
negative predictive value of complete RVR, however, was
considerably higher for HIV negative compared with coinfected
patients (50% vs 35%). |
|
The
negative predictive values of both partial RVR (63% vs 100%)
and complete EVR (82% vs 100%) were "much improved"
compared with complete RVR, both reaching 100% for coinfected
patients. |
"Despite
being generally reported to have lower rates of response to
therapy than HCV monoinfected patients," the investigators
concluded, "adherent HIV/HCV [coinfected] patients in ATAHC
achieved RVR at a similar rate to HIV negative participants
and experienced greater HCV RNA reductions between week 4 and
week 12 of therapy."
These findings, they noted, "would be consistent with an
effect of ribavirin on third-phase viral kinetics and suggest
a potential benefit for combination therapy in maximizing early
virological responses in this setting."
National Centre in HIV Epidemiology and Clinical Research
(NCHECR), University of New South Wales, Sydney, NSW; Burnet
Institute, Melbourne, Victoria; Virology Division, SEALS Microbiology,
Prince of Wales Hospital, Sydney, NSW, Australia.
5/7/10
References
GV Matthews, J Grebely, M Hellard, and others (Australian Trial
in Acute HCV Study Group). Differences in early virological
decline in individuals treated within the Australian Trial in
Acute HCV suggest a potential benefit for the use of ribavirin.
45th Annual Meeting of the European Association for the Study
of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010.
(Abstract).
GV Matthews, J Grebely, M. Hellard, and others (Australian Trial
in Acute HCV Study Group). Week 4 HCV RNA is the optimal predictor
of SVR in both HIV positive and negative subjects within the
Australian trial in acute HCV. 45th Annual Meeting of the European
Association for the Study of the Liver (EASL 2010). Vienna,
Austria. April 14-18, 2010. (Abstract).
