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  15th CROI
Conference on Retroviruses and Opportunistic Infections Boston, MA
Feb 3-6, 2008
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Week 4 or 12 Response to PegIFN Predicts Sustained Response With HCV/HIV
 
 
  15th Conference on Retroviruses and Opportunistic Infections
February 3-6, 2008
Boston
 
Mark Mascolini
 
As in people infected only with hepatitis C virus (HCV), 4- or 12-week HCV response to pegylated interferon (pegIFN) predicted sustained virologic response (SVR) in HCV/HIV-coinfected patients in the APRICOT trial [1]. Rapid virologic response (RVR) at 4 weeks proved the stronger predictor.
 
Studies in HIV-uninfected people show that 4-week RVR or 12-week complete early virologic response (EVR) predict which HCV-infected patients stand the best chance of SVR after stopping pegIFN and ribavirin for HCV infection [2,3]. To see if the same markers foretell SVR in HCV/HIV-coinfected people, APRICOT investigators ran a retrospective analysis of response rates in 289 people who took pegIFN alfa-2a (180 ug/week) plus ribavirin (800 mg/day) in that trial.
 
The analysis focused on 176 people with HCV genotype 1 and 95 with genotype 2 or 3. The APRICOT team divided them into groups with RVR (undetectable HCV RNA at week 4), complete EVR (HCV RNA detectable at week 4 but undetectable at week 12), partial EVR (HCV RNA detectable at week 4 and detectable with at least a 2-log drop at week 12), and no EVR (HCV RNA detectable at week 4 and detectable without a 2-log drop at week 12).
 
Defining SVR as undetectable HCV RNA 24 weeks after treatment stopped (study week 72), the investigators recorded the following SVRs according to 4- and 12-week responses:
 
Genotype 1 HCV:
· RVR in 22 of 176 (13%): SVR in 18 of 22 (82%)
· Complete EVR in 38 of 176 (22%): SVR in 24 of 38 (63%)
· Partial EVR in 46 of 176 (26%): SVR in 8 of 46 (17%)
· No EVR in 70 of 176 (40%): SVR in 1 of 70 (1%)
 
Genotype 2 or 3 HCV:
· RVR in 35 of 95 (37%): SVR in 33 of 35 (94%)
· Complete EVR in 33 of 95 (35%): SVR in 23 of 33 (70%)
· Partial EVR in 11 of 95 (12%): SVR in 2 of 11 (18%)
· No EVR in 16 of 95 (17%): SVR in 1 of 16 (6%)
 
SVR rates varied further depending on whether patients had bridging fibrosis or cirrhosis. Among people with HCV genotype 1 and no bridging fibrosis or cirrhosis, SVR rates were 85% in those with RVR, 64% in those with complete EVR, and 20% in those with partial EVR. Among people with HCV genotype 2 or 3 and no bridging fibrosis or cirrhosis, SVR rates measured 97% in those with RVR, 69% in those with complete EVR, and 20% in those with partial EVR.
 
APRICOT investigators did not calculate sensitivity or specificity of RVR or complete EVR in forecasting SVR with pegIFN/ribavirin. Still, they suggested clinicians can use week 4 and 12 responses "to guide treatment" in coinfected people. The investigators also called for prospective studies to determine whether physicians can combine RVR and complete EVR with baseline predictors to refine pegIFN treatment strategies, for example, by treating for 24 weeks in those with RVR and 72 weeks in those who respond more slowly.
 
References
1. Rodriguez-Torres M, Rockstroh J, Depamphilis J, et al. On-treatment responses at weeks 4 and 12 can be used to predict sustained virological response rates in HCV/HIV-co-infected patients treated with peg-interferon alfa-2a and ribavirin. 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston. Abstract 1073.
2. Marcellin P, Heathcote EJ, Craxi A. Which patients with genotype 1 chronic hepatitis C can benefit from prolonged treatment with the eaccordionf regimen? J Hepatol. 2007;47:580-587.
3. Marcellin P, Jensen D, Hadziyannis S, Ferenci P. Differentiation of early virological 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). Hepatology 2007;46(suppl 1):818A. Abstract 1308.