icon-folder.gif   Conference Reports for NATAP  
 
  58th Annual Meeting of the American Association
for the Study of Liver Diseases
(AASLD)
November 2-6, 2007
Boston, MA
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Patients co-infected with HCV and HIV who achieve an RVR (HCV RNA <50 IU/mL at week 4) or cEVR (HCV RNA <50 IU/mL at week 12) have similar rates of SVR to mono-infected patients treated with peginterferon alfa-2a (40KD) (PEGASYS) and ribavirin (COPEGUS)
 
 
  Reported by Jules Levin
AASLD, Nov 2-6, 2007, Boston, MA
 
M. Rodriguez-Torres,1 F. Torriani,2 J. Rockstroh,3 J. Depamphilis,4 G. Carosi,5 D.T. Dieterich6
1Fundacion de Investigacion de Diego, Santurce, Puerto Rico; 2University of California, San Diego, CA, USA; 3University of Bonn, Bonn, Germany; 4Roche, Nutley, NJ, USA; 5Universita Degli Studi di Brescia, Brescia, Italy; 6Mount Sinai School of Medicine, New York, NY, USA
This research was funded by Roche, Basel, Switzerland.
 
CONCLUSIONS
Approximately one third (34%) of patients infected with HCV genotype 1 and more than two thirds of those infected with HCV genotype 2 or 3 (72%) enrolled in APRICOT cleared HCV RNA from serum by 12 weeks of treatment with peginterferon alfa-2a (40KD) plus ribavirin.
 
HIV-HCV co-infected patients who achieve an RVR at week 4 or cEVR at week 12 of treatment with peginterferon alfa-2a (40KD) plus ribavirin 800 mg/day have a high chance of achieving an SVR, irrespective of HCV genotype.
 
Fewer HIV-HCV co-infected patients achieve an RVR or cEVR when compared with HCV mono-infected patients. However, the overall SVR rate in patients with HCV genotype 1 and an RVR or cEVR (70%) in APRICOT is similar to that in patients with HCV mono-infection treated with the same combination in two large phase III trials (73%).[3]
 
Studies are needed to evaluate response-guided therapy in HIV- HCV co-infected patients. In particular, the effect of intensified treatment in patients without an RVR or cEVR would be of interest.
 
INTRODUCTION
Patients with HIV-HCV co-infection have more rapid progression of liver disease and a lower probability of sustained virologic response (SVR) than patients with HCV mono-infection.[1]
 
In APRICOT, the largest trial of HCV treatment in HIV-HCV co-infected patients, the combination of peginterferon alfa-2a (40KD) plus ribavirin produced an overall SVR rate of 40% (29% in those infected with HCV genotype 1; 62% in those patients infected with genotype 2 or 3).[2]
 
In patients with HCV mono-infection, the virologic response at week 4 and 12 of treatment is increasingly being used to guide therapy decisions (response-guided therapy).
 
OBJECTIVE

The objective of this analysis is to determine the relationship between on-treatment virologic responses at week 4 and 12 of treatment and SVR rates at the end of follow-up.
 
METHODS
 
Patients

 
Adult patients eligible for APRICOT were required to have HIV-1 infection confirmed by the presence of anti-HIV antibodies or HIV RNA in serum.
 
Patients with CD4+ cell counts ≥200 cells/mm3 were eligible regardless of HIV RNA level; those with CD4+ cell counts between 100 cells/mm3 and 199 cells/mm3 were eligible if their serum HIV RNA level was <5000 copies/mL.
 
Patients were not required to be on antiretroviral therapy (ART) at the time of enrollment. If taking ART, they were required to have been on a stable regimen for at least 6 weeks. If not on ART, they were required to have been off treatment for the previous 8 weeks.
 
With respect to their HCV disease status, patients eligible for APRICOT were required to have quantifiable serum HCV RNA (≥600 IU/mL), elevated ALT levels in serum, a biopsy result consistent with the diagnosis of chronic hepatitis C, and compensated liver disease.
 
The complete inclusion and exclusion criteria and study design of APRICOT have been described elsewhere.[2]
 
Treatment
 
Patients included in this analysis were those who were randomly assigned to 48 weeks of treatment with peginterferon alfa-2a (40KD) 180 _g/week plus ribavirin 800 mg/day.
 
Outcomes
 
Virologic responses at week 4 and 12 were divided into four mutually exclusive categories (Table 1).
 

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SVR was defined as undetectable HCV RNA (<50 IU/mL) at the end of a 24-week untreated follow-up period (week 72).
 
Rates of SVR were determined as a function of response to therapy at weeks 4 and 12.
 
RESULTS
 
A total of 289 patients were included in the intent-to-treat analysis, of whom 271 patients were infected with HCV genotype 1, 2, or 3.
 
Overall, 21% (60/289) of patients achieved an RVR by week 4 of treatment, 26% (74/289) of patients had a complete EVR (cEVR), and 21% (61/289) of patients had a partial EVR (pEVR) by week 12 of treatment.
 
The distribution of SVR rates by the on-treatment virologic response are presented in Figure 1 for patients infected with HCV genotype 1 and in Figure 2 for patients infected with HCV genotype 2 or 3.
 
Figure 1. Virologic responses at week 4 and 12 in HIV-HCV (genotype 1) co-infected patients treated for 48 weeks with peginterferon alfa-2a 180 _g/week plus ribavirin 800 mg/day in APRICOT.
 

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The rate of SVR was highest in patients who had cleared HCV RNA at week 4 or 12 of treatment.
 
_ The rate of SVR was highest in patients achieving an RVR (82% in those infected with HCV genotype 1 and 94% in those infected with HCV genotype 2 or 3).
 
_ Among patients with a cEVR, the SVR rate was 63% in those infected with genotype 1 and 70% in those infected with HCV genotype 2 or 3.
 
Figure 2. Virologic responses at week 4 and 12 in HIV-HCV (genotype 2 or 3) co-infected patients treated for 48 weeks with peginterferon alfa-2a 180 _g/week plus ribavirin 800 mg/day in APRICOT.

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The rate of SVR was lowest in those with detectable HCV RNA at week 12 (i.e., in those with a pEVR or non-RVR; Figures 1 and 2).
 
Among patients with an RVR or cEVR, the rate of SVR was highest in those with a low pre-treatment HCV RNA level (<400 000 IU/mL) and in those without advanced fibrosis (Table 2).
 
Table 2. SVR rates according to on-treatment virologic response, baseline HCV RNA level, and histological diagnosis.
From Jules: Of note, SVR rates are high if RVR is achieved. In particular, if there is no bridging fibrosis/cirrhosis, 85% of genotype 1 and 97% of genotype 2/3 patients with RVR achieve SVR, but if bridging fibrosis/cirrhosis is present even with RVR rates of SVR are only 50% in genotype 1 and 67% in genotype 2/3; the number of patients with bridging fibrosis/cirrhosis are small but this suggests starting therapy before disease progression is important, starting therapy early in coinfection is important to achieve good response.

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REFERENCES
1. Alberti A, Clumeck N, Collins S, et al. Short statement of the first European Consensus Conference on the treatment of chronic hepatitis B and C in HIV co-infected patients. J Hepatol 2005; 42(5): 615-624.
2. Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 2004; 351(5): 438-450.
3. Marcellin P, Jensen D, Hadziyannis S, Ferenci P. Differentiation of early virologic response (EVR) into RVR, complete EVR (cEVR) and partial EVR (pEVR) allows for a more precise prediction of SVR in HCV genotype 1 patients treated with peginterferon alfa-2a (40KD) (PEGASYS) and ribavirin (COPEGUS). Poster presented at the 58th Annual Meeting of the American Association for the Study of Liver Diseases. November 2-6, 2007.