DAUPHINE: a randomized phase II study of danoprevir/ritonavir plus peginterferon alpha-2a/ribavirin in HCV genotypes 1 or 4.

BACKGROUND & AIMS: Danoprevir is a hepatitis C virus (HCV) protease inhibitor with activity against genotypes (G)1/G4, which is maintained at lower doses by ritonavir-boosting. We report results of a large, randomized, active-controlled phase IIb study of ritonavir-boosted danoprevir (danoprevir/r) plus peginterferon alpha-2a/ribavirin (P/R) in treatment-naive patients with HCV G1/4 infection. METHODS: Treatment-naive patients with HCV G1/4 infection were randomized to twice-daily danoprevir/r 200/100 mg (A, n = 92); 100/100 mg (B, n = 93); or 50/100 mg (C, n = 94) plus P/R for 24 weeks; twice-daily danoprevir/r 100/100 mg (D, n = 94) plus P/R for 12 or 24 weeks; or P/R alone (E, n = 44) for 48 weeks. Patients in the response-guided therapy arm (D) with an extended rapid virological response (eRVR2: HCV RNA <15 IU/ml during Weeks 2-10) stopped all therapy at Week 12; non-eRVR2 patients continued all treatment to Week 24. The primary efficacy endpoint was sustained the virological response (SVR24: HCV RNA <15 IU/ml after 24 weeks of untreated follow-up). RESULTS: SVR24 rates in Arms A, B, C, D and E were 89.1%, 78.5%, 66.0%, 69.1% and 36.4%, respectively, in the overall population; 83.6%, 69.6%, 60.3%, 59.2% and 38.5% in G1a-infected patients, 96.6%, 93.1%, 73.1%, 78.4% and 28.6% in G1b-infected patients and 100%, 87.5%, 100%, 100% and 66.7% in G4-infected patients. Danoprevir/r plus P/R was generally well tolerated compared with P/R alone. There was a higher incidence of serious adverse events in danoprevir-treatment arms, but most were associated with P/R. CONCLUSIONS: The combination of danoprevir/r plus P/R is efficacious in treatment-naïve patients with HCV genotype 1 or 4 infection.

High level antibody avidity is achieved in HIV-seropositive recipients of an inactivated split adjuvanted (AS03A) influenza vaccine.

PURPOSE: More severe influenza disease and poor vaccine immunogenicity is reported in HIV-infected patients. We measured antibody avidity after influenza vaccination in HIV patients to assess vaccine efficacy. METHODS: Two dosing strategies (Group1: single dose, n = 28. Group2: single dose plus booster, n = 36) with an AS03A-adjuvanted H1N12009 pandemic influenza vaccine (Arepanrix, GSK) were assessed in HIV patients. Serum hemagglutination inhibition (HAI) titers and antibody avidity reported as an avidity index (AI) were measured at days 21 and 42 and at 6 months. RESULTS: Baseline HIV parameters were similar among all participants. Eighteen participants had measurable baseline HAI titers. In these subjects, AI was at ~9 at baseline and was not significantly increased by one or two vaccine doses. In those without detectable baseline antibodies, immunization induced modest antibody titers [Group1 HAI, 61 (26-144); Group2 HAI, 46 (28-76)] with high AI after one dose at day 21 [Group1 AI, 8.8 (7.3-10.7); Group2 AI, 8.9 (7.8-10.1)]. A second dose of vaccine generated significantly higher HAI titers at day 42 [Group1 HAI, 41 (18-90); Group2 HAI, 92 (64-132)] and persisted to 6 months [Group1 HAI, 9 (6-13); Group2 HAI, 19 (13-30)]. All subjects who produced detectable HAI titers after vaccination generated high antibody avidity (AI, 9-10), which persisted up to 6 months. CONCLUSION: In participants initially seronegative, two doses of vaccine enabled a greater percentage of subjects to respond to the vaccine and elicited higher HAI titers. All subjects who produced detectable HAI titers also rapidly generated high AI in the short and long term. We demonstrate that high avidity antibodies can be achieved after vaccination and support a two-dose immunization strategy for HIV-positive subjects.

Randomized controlled trial of danoprevir plus peginterferon alfa-2a and ribavirin in treatment-naïve patients with hepatitis C virus genotype 1 infection.

BACKGROUND & AIMS: The combination of a hepatitis C virus (HCV) protease inhibitor, peginterferon, and ribavirin is the standard of care for patients with HCV genotype 1 infection. We report the efficacy and safety of response-guided therapy with danoprevir (a potent second-generation protease inhibitor), peginterferon alfa-2a (40 KD), and ribavirin in these patients. METHODS: Treatment-naïve patients (N = 237) were randomly assigned to groups given 12 weeks of danoprevir (300 mg every 8 hours; 600 mg every 12 hours, and 900 mg every 12 hours) or placebo plus peginterferon alfa-2a and ribavirin, followed by peginterferon alfa-2a and ribavirin. Patients given danoprevir who had an extended rapid virologic response (eRVR4-20: HCV RNA <15 IU/mL during weeks 4-20) stopped therapy at week 24; those without an eRVR4-20 continued therapy to 48 weeks. Patients who were given placebo received 48 weeks of peginterferon alfa-2a and ribavirin. The primary efficacy end point was sustained virologic response (SVR: HCV RNA <15 IU/mL after 24 weeks without treatment). RESULTS: Rates of SVR were higher among patients given danoprevir 300 mg (68%), 600 mg (85%), and 900 mg (76%) than placebo (42%) (95% confidence interval: 26%-59%). Seventy-nine percent of patients given danoprevir 600 mg had an eRVR4-20; among these, 96% had an SVR. Serious adverse events were reported in 7% to 8% of patients given danoprevir and 19% given placebo. Four patients given danoprevir (1 patient in the 600-mg group and 3 in the 900-mg group) had reversible, grade 4 increases in alanine aminotransferase, which led to early discontinuation of the 900-mg arm of the study. CONCLUSIONS: The combination of danoprevir, peginterferon alfa-2a, and ribavirin leads to high rates of SVR in patients with HCV genotype 1 infection, but high doses of danoprevir can lead to grade 4 increases in alanine aminotransferase. Studies of lower doses of danoprevir with ritonavir, to reduce overall danoprevir exposure while maintaining potent antiviral activity, are underway; Clinicaltrials.gov number, NCT00963885.

JUMP-C: a randomized trial of mericitabine plus pegylated interferon alpha-2a/ribavirin for 24 weeks in treatment-naïve HCV genotype 1/4 patients.

UNLABELLED: Mericitabine is a selective nucleoside analog inhibitor of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase, with activity across all HCV genotypes. Treatment-naïve patients infected with HCV genotype 1 or 4 were randomized to 24 weeks of double-blind treatment with either mericitabine 1,000 mg (N = 81) or placebo (N = 85) twice-daily (BID) in combination with pegylated interferon alpha-2a (Peg-IFNα-2a)/ribavirin (RBV). Patients randomized to mericitabine with HCV RNA <15 IU/mL from week 4 to 22 (extended rapid virologic response; eRVR) stopped all treatment at week 24; all other patients continued Peg-IFNα-2a/RBV to complete 48 weeks of treatment. The primary efficacy endpoint was sustained virologic response (SVR; HCV RNA <15 IU/mL after 24 weeks of treatment-free follow-up). SVR was achieved in 56.8% (95% confidence interval [CI]: 45.9-67.0) of mericitabine-treated patients and 36.5% (95% CI: 27.0-47.1) of placebo-treated patients (Δ = 20.3%; 95% CI 5.5-35.2). SVR rates were higher in mericitabine- than placebo-treated patients when subdivided by IL28B genotype (CC, 77.8% versus 56.0%; non-CC, 44.1% versus 16.2%) and hepatic fibrosis (noncirrhotic, 63.3% versus 41.9%; cirrhotic, 38.1% versus 21.7%). Overall relapse rates were 27.7% and 32.0% in mericitabine- and placebo-treated patients, respectively. No evidence of NS5B S282T-variant virus or phenotypic resistance to mericitabine was observed in the one patient who experienced partial response. No S282T variants were detected in any baseline samples. The safety profile of mericitabine was similar to that of, and fewer patients in the mericitabine than in the placebo group discontinued treatment for safety reasons. CONCLUSION: A 24-week response-guided combination regimen of mericitabine 1,000 mg BID plus Peg-IFNα-2a/RBV is well tolerated and more effective than a standard 48-week course of Peg-IFNα-2a/RBV.

Citalopram for the prevention of depression and its consequences in HIV-hepatitis C coinfected individuals initiating pegylated interferon/ribavirin therapy: a multicenter randomized double-blind placebo-controlled trial.

BACKGROUND: Depression related to interferon-alpha (IFN-α) is common, may reduce adherence, and can be treatment limiting. HIV-HCV coinfected persons experience lower sustained virologic response rates and commonly have psychiatric comorbidities, thus they may benefit from prevention of depression. OBJECTIVE: The aim of the study was to determine whether prophylactic citalopram can increase HCV treatment adherence and reduce the incidence of moderate depression in HIV-HCV coinfected patients initiating PEG-IFN-α/ribavirin therapy. METHODS: This was an investigator-initiated Canadian multicenter randomized, double-blind placebo-controlled trial. HIV-HCV coinfected patients were randomized in a 1:1 ratio to receive citalopram or placebo 3 weeks prior to starting PEG-IFN-α2b/ribavirin, stratified by study center and HCV genotype. The protocol design permitted the comparison of prophylaxis with the treatment of emergent depression. The primary outcomes were adherence (assessed through questionnaire and returned medication) and time to moderate depression measured by Beck Depression Inventory-II (BDI- II) score greater than 15, confirmed 2 weeks apart. RESULTS: Seventy-six patients (36 citalopram/40 placebo) were randomized. Overall adherence was high, ranging from 95% (week 12) to 91% (week 48). There was no difference between arms with respect to mean or median adherence at any study time point. Cumulative incidence of moderate depression did not differ significantly by group (log rank P = .32). The hazard ratio for moderate depression was 0.81 (95% CI, 0.26 to 2.54) for citalopram compared with placebo when adjusted for baseline BDI-II score. CONCLUSIONS: A strategy of prophylactic citalopram compared to treatment of emergent depression was not associated with higher adherence or a reduction in treatment-limiting depression nor did it significantly reduce depressive symptoms among HIV-HCV coinfected persons during treatment for HCV.

Efficacy and safety of pegylated interferon alfa-2a or alfa-2b plus ribavirin for the treatment of chronic hepatitis C in children and adolescents: a systematic review and meta-analysis.

BACKGROUND: A systematic review and meta-analysis were conducted to examine the efficacy and safety of pegylated interferon (peg-IFN) alfa-2a and peg-IFN alfa-2b plus ribavirin (RBV) in children and adolescents with chronic hepatitis C virus (HCV). METHODS: Medline, Embase, and Cochrane Central Register of Controlled Trials were searched. Clinical trials examining peg-IFN alfa-2a or peg-IFN alfa-2b plus RBV among persons ages 3-18 years with HCV were included. Data were abstracted for complete early virologic response (EVR), sustained virologic response (SVR), relapse, treatment discontinuations, hematologic and dermatologic adverse events, and growth inhibition. RESULTS: Eight trials met the inclusion criteria. Results indicate that 70% of subjects (95% confidence interval [CI], 58%-81%) achieved EVR, and 58% (95% CI, 53%-64%) achieved SVR. EVR and SVR were higher for those with HCV genotypes 2/3 than 1/4. Discontinuation due to adverse events and discontinuation due to viral breakthrough were each 4%, discontinuation due to a lack of response was 15%, and relapse was 7%. Anemia, neutropenia, leukopenia, and thrombcytopenia were 11%, 32%, 52%, and 5%, respectively. Alopecia, injection site erythema, and pruritus were 13%, 27%, and 10%, respectively. Small growth inhibitions were observed during treatment. CONCLUSION: The results of this meta-analysis indicate that peg-IFN/RBV combination treatment is effective and safe in treating children and adolescents with HCV.

Outcomes of chronic hepatitis C therapy in patients treated in community versus academic centres in Canada: final results of APPROACH (a prospective study of peginterferon alfa-2a and ribavirin at academic and community centres in Canada).

BACKGROUND: In patients chronically infected with the hepatitis C virus (HCV), it is not established whether viral outcomes or health-related quality of life (HRQoL) differ between individuals treated at academic or community centres. METHODS: In the present observational study, adults with chronic HCV were treated with peginterferon alfa-2a 180 ìg/week plus ribavirin at 45 Canadian centres (16 academic, 29 community). The primary efficacy end point was sustained virological response (SVR). Other outcome measures included HRQoL (assessed using the 36-item Short-Form Health Survey), heath resource use, and workplace productivity and absences within a 60-day interval. RESULTS: In treatment-naive patients infected with HCV genotype 1, significantly higher SVR rates were achieved in those treated at academic (n=54) compared with community (n=125) centres (52% versus 32% [P=0.01]), although rates of dosage reduction and treatment discontinuation were similar across settings. SVR rates among patients infected with genotype 2/3 were similar between academic (n=59) and community (n=100) centres (64% versus 67% [P=0.73]). Following antiviral therapy, patients with genotype 1 who achieved an SVR (n=67) had significantly higher mean scores on the physical (P=0.005) and mental components of the 36-item Short-Form Health Survey (P=0.043) compared with those without an SVR (n=111). In contrast, HRQoL scores were similar in HCV genotype 2/3 patients with and without an SVR. There were no differences in workplace productivity or absences between patients with and without an SVR. The most frequently used health care resources by all patients were visits and phone calls to hepatitis nurses, and general practice or walk-in clinics. CONCLUSION: Patients infected with HCV genotype 1 achieved higher SVR rates when treated at academic rather than community centres in Canada. The reasons for this difference require additional investigation.

Is pre-treatment liver biopsy necessary for all hepatitis C genotypes?

BACKGROUND: Current practice guidelines recommend liver biopsy prior to treatment of hepatitis C genotype-1 but not for genotype-2/3; this is based on expert opinion, not on published evidence. METHODS: In retrospective analysis of a large trial database prior to the publication of recent guidelines, we compared outcomes in 985 treatment-naïve patients with hepatitis C who did or did not undergo liver biopsy before starting peginterferon alfa-2a plus ribavirin. RESULTS: Physicians elected to treat 141/654 (21.6%) genotype-1 patients and 126/331 (38.1%) genotype-2/3 patients without liver biopsy. There were no differences in baseline characteristics among those with or without pre-treatment liver biopsy, except for female preponderance in genotype-1 patients with liver biopsy. The sustained viral response (SVR) rate was no different amongst genotype-2/3 patients who had a biopsy before treatment with 66.3% SVR vs. 69.8% of those treated without biopsy (p = 0.546), but significantly higher among genotype-1 patients with pre-treatment liver biopsy at 54.6 vs. 44.0% for those treated without a liver biopsy (p = 0.029). In genotype-1 patients with liver biopsy, more patients with cirrhosis had dose adjustments (p = 0.0057) rather than drug discontinuation. There was tendency for earlier discontinuation among patients without pre-treatment liver biopsy. CONCLUSIONS: Pre-treatment liver biopsy was associated with better SVR amongst genotype-1 patients. This improvement may reflect ongoing commitment to completing the treatment course by both patient and physician. In genotype-2/3 patients, pre-treatment liver biopsy may not be essential to maximize SVR rates. This study validates the recommendations of the most recent treatment guidelines for hepatitis C.

Outcomes of peginterferon alpha-2a and ribavirin hepatitis C therapy in Aboriginal Canadians.

BACKGROUND: There is little published information on baseline characteristics and therapeutic outcomes in hepatitis C virus (HCV)-infected Aboriginal Canadians. It is unclear what proportion of HCV-infected Aboriginal people receive therapy relative to other populations. METHODS: Adults with chronic HCV infection, quantifiable serum HCV-RNA levels and compensated liver disease were assigned, at the physician's discretion, to either 24 or 48 weeks of treatment with peginterferon alpha-2a 180 mug/week plus ribavirin at a dose of 800 mg/day, or 1000 mg/day or 1200 mg/day in an open-label, expanded access program. The primary outcome was sustained virological response, defined as undetectable HCV-RNA by qualitative polymerase chain reaction (less than 50 IU/mL) at the end of 24 weeks of untreated follow-up. Baseline characteristics and outcomes in Aboriginal and non-Aboriginal patients were compared. RESULTS: A total of 2614 patients were eligible for the analysis; 44 individuals (1.7%) self-identified as being of Aboriginal heritage. The baseline characteristics of these two groups were similar. An overall sustained virological response was achieved in 47.7% and 46.5% of Aboriginal and non-Aboriginal patients, respectively. The overall frequencies of adverse events and laboratory abnormalities were similar between the two groups, although cytopenias occurred less frequently in Aboriginal patients. INTERPRETATION: Aboriginal patients were greatly under-represented in the present 'community'-based treatment program, yet viral responses were similar to those of a non-Aboriginal cohort. To increase the uptake of HCV therapy in the Aboriginal population, clarification of the obstacles to treatment is warranted.

Rate of infectious complications during interferon-based therapy for hepatitis C is not related to neutropenia.

The relationship between infectious complications and neutropenia was evaluated in recipients of interferon-based therapy for hepatitis C followed at The Ottawa Hospital Viral Hepatitis Clinic from June 2000 to May 2005. One hundred ninety-two patients received 211 courses of therapy (5707 person-weeks of therapy). No patients received granulocyte colony-stimulating factor. Sixty-seven infectious complications occurred in 57 patients (1.17 infections per 100 person-weeks of therapy). The median time to infection was 17 weeks after the start of therapy. Age, sex, weight, race, human immunodeficiency virus status, stage and grade of biopsy, and type of interferon were not correlated with infection rate by Cox regression analysis. The rates of total, fungal, viral, and bacterial infections did not correlate with nadir neutrophil count or magnitude of decrease from baseline. Neutrophil count is not correlated with infection rate in recipients of interferon-based therapy for hepatitis C. Reduction in interferon dose and/or dosing with granulocyte colony-stimulating factor in those with neutropenia is not supported by this analysis.

Infection rates in HIV-HCV patients treated with interferon are similar to those in HCV mono-infection and not related to neutropenia.

METHOD: Infectious complications were assessed in 25 HIV-HCV coinfected patients receiving 29 courses of HCV therapy (786 person-weeks). RESULTS: The infection rate (1.3 infections/100 person-weeks) was similar when compared to the rate in HIV-negative patients. HIV status and neutrophil nadir did not predict infection risk or rate. CONCLUSION: Interferon dose reduction and/or G-CSF in HCVtreated HIV patients with neutropenia are not justified.

Single-dose infliximab in hepatitis C genotype 1 treatment-naive patients with high serum tumour necrosis factor-alpha does not influence the efficacy of pegylated interferon alpha-2b/ribavirin therapy.

BACKGROUND: Serum tumour necrosis factor-alpha (TNF-α) levels correlate negatively with hepatitis C virus (HCV) antiviral response. OBJECTIVES: To test the hypothesis that a single infliximab induction dose would positively influence on-treatment virological response and sustained virological response (SVR). METHODS: The present study was a phase IIIB, randomized, prospective, open-label pilot trial conducted at eight Canadian sites. Treatment-naive HCV genotype 1-infected patients 18 to 65 years of age with high serum TNF-α values (>300 pg/mL) were randomly assigned to receive a single pretreatment induction infliximab infusion (5 mg/kg) seven days before antiviral therapy (arm A) or no pretreatment (arm B). All patients received pegylated interferon α2b (1.5 µg/kg/week) plus weight-based ribavirin (800 mg/day to 1400 mg/day) for up to 48 weeks. RESULTS: Eighty-five patients (arm A [n=41], arm B [n=44]; 70% male) received pegylated interferon α2b. The mean age (48.1 years), race (81% white) and METAVIR fibrosis stage (F0-2 = 79%, F3-4 = 21%) were similar between groups. Infliximab was well tolerated without attributable severe adverse events; 56.5% completed the study (arm A [n=21], arm B [n=27]). Most discontinuations were due to virological failure at weeks 12 (n=20 [23.5%]) and 24 (n=7 [8.2%]) and did not differ according to group. Numerically lower proportions of infliximab recipients achieved rapid virological response (19.5% versus 36.4%), complete early virological response (43.9% versus 59.1%) and SVR (34.1% versus 52.3%). However, between-group differences did not reach statistical significance. No differences in adverse event profile or laboratory measures were noted. CONCLUSION: A single infliximab dose before pegylated-interferon α2b and ribavirin therapy did not result in greater viral decline during the first 12 weeks of HCV therapy or improved SVR.

Boceprevir versus placebo with pegylated interferon alfa-2b and ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a randomised, double-blind, controlled phase 2 trial.

BACKGROUND: Rates of sustained virological response (SVR) to peginterferon-ribavirin are low in patients with hepatitis C virus (HCV) genotype 1 and HIV. We aimed to assess efficacy and safety of triple therapy with boceprevir plus pegylated interferon alfa-2b (peginterferon) and ribavirin, which increases rates of SVR in patients with HCV alone. METHODS: In our double-blind, randomised controlled phase 2 trial, we enrolled adults (18-65 years) with untreated HCV genotype 1 infection and controlled HIV (HIV RNA <50 copies per mL) at 30 academic and non-academic study sites. We randomly allocated patients (1:2) according to a computer generated sequence, stratified by Metavir score and baseline HCV RNA level, to receive peginterferon 1·5 µg/kg per week with weight-based ribavirin (600-1400 mg per day) for 4 weeks, followed by peginterferon-ribavirin plus either placebo (control group) or 800 mg boceprevir three times per day (boceprevir group) for 44 weeks. Non-nucleoside reverse-transcriptase inhibitors, zidovudine, and didanosine were not permitted. The primary efficacy endpoint was SVR (defined as undetectable plasma HCV RNA) at follow-up week 24 after end of treatment. We assessed efficacy and safety in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00959699. FINDINGS: From Jan 15, 2010, to Dec 29, 2010, we enrolled 99 patients, 98 of whom received at least one treatment dose. 40 (63%) of 64 patients in the boceprevir group had an SVR at follow-up week 24, compared with ten (29%) of 34 control patients (difference 33·1%, 95% CI 13·7-52·5; p=0·0008). Adverse events were more common in patients who received boceprevir than in control patients: 26 (41%) versus nine (26%) had anaemia, 23 (36%) versus seven (21%) pyrexia, 22 (34%) versus six (18%) decreased appetite, 18 (28%) versus five (15%) dysgeusia, 18 (28%) versus five (15%) vomiting, and 12 (19%) versus two (6%) neutropenia. Three patients who received boceprevir plus peginterferon-ribavirin and four controls had HIV virological breakthrough. INTERPRETATION: Boceprevir in combination with peginterferon-ribavirin could be an important therapeutic option for patients with HCV and HIV. FUNDING: Merck.

Management of adverse effects of Peg-IFN and ribavirin therapy for hepatitis C.

HCV infects approximately 2-3% of the global population and is a leading cause of end-stage liver disease and hepatocellular carcinoma. Treatment of HCV infection with Peg-IFN in combination with ribavirin can eradicate HCV infection in 40-90% of patients; however, a major barrier to treatment uptake and delivery is the association of this therapy with frequent and, at times, serious adverse effects. Recognition and effective management of these adverse effects are critical components of the successful treatment of chronic HCV infection. In clinical trials, approximately 10-15% of patients discontinue Peg-IFN and ribavirin therapy due to adverse effects; however, in clinical practice, the rate of treatment discontinuation has been reported to be substantially higher. The off-target effect of Peg-IFN and ribavirin impacts most, if not all, organ systems; the most common adverse effects are hematologic, dermatologic, neurologic, immunologic, gastrointestinal, pulmonary, cardiovascular, and ocular. Regional and global variability exists in the nature of these adverse effects and the strategies employed to ameliorate their impact. This article provides a comprehensive literature review that systematically describes the adverse effects of Peg-IFN-α and ribavirin on various organ systems and, more importantly, recommends consensus approaches to managing those effects.

Identifying HCV genotype 1 patients at risk of relapse.

OBJECTIVE: The objective of this analysis was to identify predictors of relapse in genotype 1 patients after 48 weeks of treatment with peginterferon plus ribavirin. METHODS: Retrospective analysis of data from treatment-naive genotype 1 patients with an end-of-treatment response after 48 weeks of treatment with peginterferon alpha-2a plus ribavirin 1000/1200 mg/day in the Canadian Pegasys Expanded Access Program. RESULTS: Among treatment-naive genotype 1 patients with an end-of-treatment response (n = 432), the sustained virological response status was known for 405 individuals (sustained virological response n = 328, 81%; relapse n = 77, 19%). Early virological response rates at week 12 were similar in relapsers (98.7%) and sustained responders (98.5%). More relapsers (12 of 77, 15.6%) than sustained responders (15 of 328, 4.6%) had quantifiable hepatitis C virus (HCV) RNA (>or=600 IU/ml) at week 12 and, among these patients, mean and maximum HCV RNA levels were higher in relapsers, although the median values were similar. Factors significantly associated with relapse in the multiple logistic regression analysis include older age (odds ratio: 1.48 per decade, 95% confidence interval: 1.06-2.07; P = 0.023), Caucasian ethnicity (odds ratio: 3.23, confidence interval: 1.25-8.33; P = 0.016), higher baseline serum HCV RNA level (P = 0.005), the drop in HCV RNA between baseline and week 12 (P = 0.026), and the interaction between baseline HCV RNA level and the decrease in HCV RNA between baseline and week 12 (P = 0.032). CONCLUSION: Older age, Caucasian ethnicity, and high baseline HCV RNA level, and a smaller decrease in HCV RNA between baseline and week 12 predict a relapse in genotype 1 patients.