05G. VIRAL HEPATITIS – G) HEPATITIS C – CLINICAL (THERAPY) S313 834 ANTIVIRAL ACTIVITY AND CHANGES IN B-LYMPHOCYTE STIMULATOR PROTEIN LEVELS DURING TREATMENT WITH ALBINTERFERON ALFA-2B/RIBAVIRIN IN PRIOR INTERFERON-THERAPY NONRESPONDERS V. Rustgi 1 , D. Nelson 2 , V. Balan 3 , M. Sulkowski 4 , J.G. McHutchison 5 , M. Fiscella 6 , P. Cronin 6 , E. Pulkstenis 6 , G.M. Subramanian 6 . 1 Metropolitan Research, Arlington, VA, 2 Division of Gastroenterology, Hepatology, and Nutrition, University of Florida College of Medicine, Gainesville, FL, 3 Hepatobiliary Clinic, Mayo Clinic, Scottsdale, AZ, 4 Johns Hopkins University School of Medicine, Baltimore, MD, 5 Duke Clinical Research Institute, Durham, NC, 6 Human Genome Sciences, Inc, Rockville, MD, USA E-mail: hepgi@aol.com Background and Aims: A phase 2 study evaluated efficacy/safety of albinterferon alfa-2b (alb-IFN)/RBV treatment for CHC in nonresponders (NRs) to IFNa-based regimens. B-lymphocyte stimulator (BLyS) is essen- tial in vivo regulator of B-lymphocyte homeostasis. The relation between serum BLyS levels and antiviral response in CHC patients was assessed. Methods: Previous NRs (failed to clear HCV-RNA or achieve EVR12) were randomized to 3 alb-IFN treatment cohorts (900 and 1200mcg q2wk, and 1200mcg q4wk) plus weight-based oral RBV 1000–1200 mg/d. Higher-dose alb-IFN groups (1500 and 1800mcg q2wk) were then enrolled sequentially. Treatment duration: 48wk; primary efficacy endpoint: SVR at 24wk post-treatment. Serum BLyS levels were assessed pretreatment, wks12, 24, and 48, and wk12 after treatment. Results: Baseline characteristics, antiviral response, and serum BLyS lev- els (N = 115) are shown (table). Higher-dose groups demonstrated greater reductions in HCV RNA at wk24 in prior genotype 1 PEG-IFN/RBV NRs. SVR rates: 17% (20/115) overall; 11% (8/75) in genotype 1 PEG-IFN/RBV NRs. Serum BLyS levels did not correlate with antiviral response or baseline characteristics. Induction of BLyS levels during treatment showed a dose-response trend and increased over time. Conclusions: Higher doses of alb-IFN demonstrated greater antiviral activity and induction of BLyS levels in prior IFNa NRs. 1200 mg 900 mg 1200 mg 1500 mg 1800 mg q4wk q2wk q2wk q2wk q2wk (n = 24) (n = 23) (n = 24) (n = 22) (n = 22) Baseline Mean HCV RNA log 10 (IU/ml) 6.2 6.7 6.5 6.9 7.4 G1, PEG-IFN/RBV NR 13 (54%) 13 (56%) 16 (67%) 15 (68%) 18 (82%) Serum BLyS, ng/mL 0.9 1.0 1.0 0.9 1.0 (% >LOQ) (33%) (39%) (54%) (36%) (64%) SVR Overall 25% 30% 13% 9% 9% G1, PEG-IFN/RBV NR 15% 15% 13% 7% 6% Mean wk-24 HCV RNA reduction, log 10 (IU/mL) 2.1 2.6 2 3.2 4.5 Wk-12 BLyS change, ng/mL 0.6 (67%) 1.5 (150%) 1.8 (178%) 1.5 (161%) 1.9 (183%) Wk-24 BLyS change, ng/mL 0.8 (87%) 2.0 (189%) 2.1 (210%) 2.0 (211%) 2.4 (252%) 835 TIME TO HCVRNA UNDETECTABILITY SUPERSEDES BASELINE FACTORS IN PREDICTING SVR IN PATIENTS WITH HCV GENOTYPE 1 M.L. Shiffman 1 , R.T. Chung 2 , F.M. Hamzeh 3 . 1 Virginia Commonwealth University, Richmond, VA, 2 Massachusetts General Hospital, Boston, MA, USA; 3 Roche Laboratories, Nutley, NJ, USA E-mail: mshiffma@vcu.edu Background and Aims: Cirrhosis, high baseline viral load, non-Caucasian race/ethnicity and body weight have been regarded as predictors of non- response in patients chronically infected with HCV genotype 1. More recently, time to become HCVRNA undetectable has been recognized as a predictor of SVR. The present analysis tested whether SVR was similar in patients who became HCVRNA undetectable at a given time during treatment, regardless of baseline characteristics. Methods: Data from 1243 HCV genotype-1 patients in 4 clinical trials treated with 180 mg/wk pegIFNa-2a/1000–1200 mg/d RBV were assessed for HCVRNA undetectability at weeks 4 (RVR), 12 (cEVR, undetectable at weeks 5-12), 24 (24Neg, undetectable at weeks 13-24), and 72 (SVR). Multiple logistic regression analysis with P < 0.02 was used to determine the effect on SVR of baseline prognostic factors and time of HCV RNA undetectability. Results: The Table shows SVR rates relative to HCVRNA undetectability at each time point and to baseline characteristics. Multiple logistic regres- sion analysis demonstrated that time to become HCV RNA undetectable was the most important factor contributing to SVR (RVR vs cEVR, OR 1.51, CI 1.02-2.25, P = 0.0401; RVR vs 24 Neg, OR 5.13, CI 3.23-8.25, P < 0.0001). Baseline HCV RNA (400,000 vs >400,000 IU/ml, OR 1.5, CI 1.02-2.20, P = 0.0389), race/ethnicity (non-Latino Caucasian vs other, OR 1.3, CI 0.94-1.79, P = 0.1075), and cirrhosis classification (non- cirrhotic vs cirrhotic, OR 1.38, CI 0.90-2.09, P = 0.1350) also contributed to SVR, but to a lesser degree. Conclusions: Time to HCV RNA undetectability was the most important predictor of SVR and may be the only predictor needed if HCVRNA is assessed frequently. Measuring HCVRNA at regular intervals during treatment is essential to optimize SVR in patients infected with HCV genotype 1. Table. SVR relative to HCV RNA undetectability at weeks 4, 12 and 24 and to baseline characteristics HCV RNA Undetectability Week 4 Week 12 Week 24 (n = 195) (n = 505) (n = 194) All (N = 1243) 146 (75) 320 (63) 64 (33) Race/ethnicity Caucasian 106 (76) 239 (67) 40 (34) Latino 28 (74) 51 (49) 17 (32) Black 4 (67) 19 (73) 5 (28) Cirrhosis classification Cirrhotic 15 (75) 34 (55) 12 (34) Non-Cirrhotic 131 (75) 286 (65) 52 (33) Baseline [HCV RNA], UI/ml 400,000 76 (78) 63 (72) 7 (41) >400,000 70 (71) 257 (62) 57 (32) Number (%) relative to number of patients in each category at each time point. 836 DIFFERENCES IN VIROLOGIC RESPONSE PATTERNS BETWEEN HIV/HCV CO-INFECTED AND HCV MONO- INFECTED PATIENTS TREATED WITH PEGINTERFERON AND RIBAVIRIN WITH DOSE ADJUSTED TO BODY WEIGHT (1000–1200 MG/DAY) C. Tural 1 , J.A. Galeras 3 , R. Planas 2 , S. Coll 3 , A. Jou 1 , I. Cirera 3 , G. Sirera 1 , M. Garcia-Retortillo 3 , J. Tor 1 , B. Clotet 1 , R. Sola 3 . 1 HIV Clinical Unit, Internal Medicine Service, 2 Hepatology Unit, Hospital Universitari Germans Trias I Pujol, Badalona, Barcelona, 3 Liver Section, Hospital Del Mar, Barcelona, Spain E-mail: 35783m@imas.imim.es The lesser effectiveness of treatment with peg-interferon (PegIFN) and ribavirin (RBV) among HIV/HCV co-infected patients might be due to the fixed RBV dose (800 mg/day) used among these people instead of the adjusted to body weight RBV dose used in mono-infected patients.