Rapid Viral Response Research Articles

Failure of Pre-Emptive Treatment of Cytomegalovirus Infections and Antiviral Resistance in Stem Cell Transplant Recipients

Treatment of cytomegalovirus (CMV) infections after stem cell transplantation (SCT) does not always lead to a rapid viral response. The causes of treatment failure may be either viral resistance or immunological failure to control viral replication. This study investigated the response to pre-emptive treatment in CMV infections in order to define risk factors for treatment failure, including the role of antiviral resistance. Adult recipients of allogeneic T-cell depleted SCT were studied retrospectively (n=92). CMV infections were treated with (val)ganciclovir according to a CMV DNA-load-based pre-emptive strategy. Treatment failure was defined as a CMV DNA load of 1,000 copies/ml or more after at least 2 weeks of treatment. Resistance was analysed by nucleotide sequence analysis of the UL97 and UL54 genes in the first CMV DNA-positive sample and in samples during treatment failure. Treatment failure occurred in 26 of the 47 pre-emptively treated patients (55%) and in 39 of 86 (45%) treatment episodes. The risk of treatment failure was increased during first treatment episodes (P=0.01) and during the use of immunosuppressive medication (P=0.02). Antiviral resistance was found in only 1 patient (4%) with treatment failure. A slow response to pre-emptive antiviral treatment occurred frequently in CMV infections in SCT recipients. Antiviral resistance was observed but played a minor role in treatment failure.

Treatment of patients with genotype 3 chronic hepatitis C‐ current and future therapies

Genotype 3 is a common type of HCV infection, and standard therapy using pegylated interferon (PEG-IFN) and ribavirin (RBV) is quite effective in these patients. While a short course of 16 weeks may result in comparable end of therapy responses, relapse rates are often high. A 24-week course is therefore preferable, and is expected to result in sustained virological response (SVR) rates of more than 70%. The 24-week course is especially recommended in the presence of steatosis (often associated with Genotype 3 infection), fibrosis stage two or more, high BMI and high viral load. In patients who do not achieve a rapid viral response (RVR) with combination therapy, an extended course up to 48 weeks should be considered. While not as definite as for genotype 1 patients, the presence of the CC variant of IL28b could help in the initial prognosis and the need for additional treatment, if an RVR is not achieved. The role of directly acting antiviral agents (DAA) has not been fully evaluated in treatment naïve, non-responders and relapsers in genotype 3 patients. Initial results with the cyclophilin inhibitor Debio-025 are quite encouraging. There is an urgent need for large clinical trials using DAA and host modulators in patients with G3 infection.

IL28B and interferon‐gamma inducible protein 10 for prediction of rapid virologic response and sustained virologic response in HIV‐HCV‐coinfected patients

A polymorphism near the IL28B gene has been shown to be associated with virologic response to antiviral treatment in HCV-infected patients. The predictive value of interferon-gamma inducible protein 10 (IP10) on treatment outcome has been described in HCV patients. Data on combining these predictors in HIV-HCV-coinfected patients are not available. Virologic parameters, IL28B single nucleotide polymorphisms (SNP) and pretreatment serum IP10 were determined in HIV-HCV-coinfected patients having completed antiviral therapy with pegylated interferon/ribavirin. A total of 72 HIV-HCV-coinfected patients were included in the study; 68% had HCV genotype (GT)-1/4 and 32% had HCV GT-2/3 infections. Rapid virologic response (63% vs. 28%; P = 0·023) and sustained virologic response (SVR: 81% vs. 51%; P = 0·008) rates were significantly higher in C/C vs. non-C/C patients. Patients with low pretreatment IP10 levels (< 400 pg/mL) achieved significantly higher SVR rates than patients with high (> 400 pg/mL) IP10 levels (78% vs. 13%; P < 0·0001). C/C SNP and low IP10 levels were associated with higher SVR rates in both patients with GT-1/4 and GT-2/3. The C/C patients with low IP10 achieved SVR rates of 97% compared with SVR rates of 9% in non-C/C patients with high IP10. The IL28B SNP influences rapid viral response, relapse rates and SVR. The combination of IL28B and IP10 represents a predictive model of SVR in HIV-HCV coinfection.

Rapid Viral Response of Once-Daily Tmc435 plus Pegylated Interferon/Ribavirin in Hepatitis C Genotype-1 Patients: A Randomized Trial

Antiviral activity of TMC435, an oral, once-daily, HCV NS3/4A protease inhibitor, was evaluated with pegylated interferon-α2a/ribavirin (P/R) in HCV genotype-1 patients. Optimal Protease inhibitor Enhancement of Response to TherApy (OPERA-1; TMC435-C201; NCT00561353) is a Phase IIa, randomized, placebo-controlled study. Treatment-naive patients (n=74) received 25, 75 or 200 mg TMC435 once daily, or placebo for 7 days followed by 21 days of triple therapy with P/R, or triple therapy for 28 days. Treatment-experienced patients (n=37; 56.8% with cirrhosis) received 75, 150 or 200 mg TMC435 once daily, or placebo with P/R for 28 days. Patients continued P/R up to week 48. Treatment-naive patients who received initial monotherapy had a rapid decline in HCV RNA by day 3. At day 7, HCV RNA reductions were greatest for the 75 and 200 mg doses (0.02, -2.63, -3.43 and -4.13 log(10) IU/ml for placebo, and TMC435 25, 75 and 200 mg, respectively). At day 28, all patients who received triple therapy with TMC435 75 or 200 mg had HCV RNA<25 IU/ml versus 4/9 for placebo. In total, 18/28 treatment-experienced patients (9/9 prior relapsers, 9/19 non-responders) who received TMC435 had HCV RNA<25 IU/ml at day 28 versus 0/9 for placebo; similar results were observed for the 150 and 200 mg doses. Most adverse events were grade 1/2. No relevant changes in laboratory parameters occurred, except mild and reversible bilirubin elevations, mostly at the 200 mg dose. Once-daily TMC435 with P/R showed potent, dose-dependent antiviral activity over 28 days, and had a favourable tolerability profile.

Peginterferon alfa‐2b plus weight‐based ribavirin for 24 weeks in patients with chronic hepatitis C virus genotype 1 with low viral load who achieve rapid viral response

In chronic hepatitis C (CHC), treatment duration may be individualized according to time to first undetectable hepatitis C virus (HCV) RNA, with patients who attain undetectable HCV RNA early in treatment being candidates for shorter regimens. The aim of this study was to determine the relapse rate in patients with CHC genotype (G) 1 infection and low baseline viral load who achieved undetectable HCV RNA by week 4 [rapid virologic response (RVR)] when treated for 24 weeks. This was an open-label, multicentre, noninterventional study. Adult patients with G1 CHC infection and baseline viral load <600,000 IU/mL who attained RVR were treated with peginterferon alfa-2b (1.5 μg/kg/week) plus ribavirin (800-1200 mg/day) for 24 weeks, then followed for a further 24 weeks. The primary endpoint was relapse rate, defined as the proportion of patients with undetectable HCV RNA at treatment week 24 and detectable HCV RNA at week 24 follow-up. The secondary efficacy endpoint was sustained virologic response (SVR). Overall, 170 patients were included in the efficacy-evaluable population. The relapse rate was 9.7% (16/165, 95% confidence interval: 0.06-0.15), and SVR was attained by 149 of 170 patients (87.6%). Virologic outcomes were consistent regardless of age, gender, body weight and genotype. Seven patients reported treatment-emergent serious adverse events (AEs), and four patients discontinued treatment because of an AE. This study further demonstrates that peginterferon alfa-2b plus weight-based ribavirin for 24 weeks is an effective treatment strategy for treatment-naive patients with G1 CHC and low viral load who attain RVR.

P70 Telaprevir in combination with peginterferon and ribavirin in genotype 1 HCV Treatment-Naïve patients: final results of phase 3 ADVANCE Study

AimThe ADVANCE study is a 3-arm double-blind, randomised, placebo-controlled Phase 3 study assessing efficacy and safety of two telaprevir (TVR, T)-based response-guided regimens compared with peginterferon alfa-2a 180 _g/week and...

Effects of mutation number in interferon sensitivity determining region on peripheral blood CD4+ T cell subsets (Th1, Th2) in chronic hepatitis C patients with hepatitis C virus genotype 1b and high viral load

The number of amino acid (AA) mutations in the interferon sensitivity determining region (ISDR) of NS5A is reported to affect the response to interferon (IFN) therapy in patients with chronic hepatitis C (CHC). The aim of this study was to clarify whether host immunity is influenced by the number of AA mutations in the ISDR. Subjects included 44 patients with CHC infected with genotype 1b and high viral load. The number of AA mutations in the ISDR was retrospectively determined using stored serum samples taken immediately before starting therapy. All patients received IFN-alpha 2b or pegylated-IFN (PEG-IFN)-alpha 2b and ribavirin. When serum hepatitis C virus-ribonucleic acid (HCV-RNA) was negative at 4 or 12weeks after starting therapy, the patient was defined as having rapid viral response (RVR) or early viral response (EVR), respectively. CD4(+) T cell (Th1 or Th2) in peripheral blood (PB) before and until day 56 of treatment was analyzed. Rates of RVR and EVR were 0 (0/21) and 14% (3/21), respectively, in patients with one or fewer AA mutations in the ISDR (ISDR0-1), and 30 (7/23), and 74% (17/23), respectively, with two or more AA mutations in the ISDR (ISDR>2). Although the percentage of PB Th1 cells did not differ between the two groups during the study period, the percentage of PB Th2 cells was significantly lower in the ISDR0-1 group than in the ISDR>2 group at baseline and on days3, 7, 14, and 28 of treatment. The number of AA mutations in the ISDR influenced PB Th2 cells before and until day 28, and was associated with higher RVR and EVR rates.

IL28B But Not ITPA Polymorphism Is Predictive of Response to Pegylated Interferon, Ribavirin, and Telaprevir Triple Therapy in Patients With Genotype 1 Hepatitis C

Pegylated interferon, ribavirin, and telaprevir triple therapy is a new strategy expected to eradicate the hepatitis C virus (HCV) even in patients infected with difficult-to-treat genotype 1 strains, although adverse effects, such as anemia and rash, are frequent. We assessed efficacy and predictive factors for sustained virological response (SVR) for triple therapy in 94 Japanese patients with HCV genotype 1. We included recently identified predictive factors, such as IL28B and ITPA polymorphism, and substitutions in the HCV core and NS5A proteins. Patients treated with triple therapy achieved comparatively high SVR rates (73%), especially among treatment-naive patients (80%). Of note, however, patients who experienced relapse during prior pegylated interferon plus ribavirin combination therapy were highly likely to achieve SVR while receiving triple therapy (93%); conversely, prior nonresponders were much less likely to respond to triple therapy (32%). In addition to prior treatment response, IL28B SNP genotype and rapid viral response were significant independent predictors for SVR. Patients with the anemia-susceptible ITPA SNP rs1127354 genotype typically required ribavirin dose reduction earlier than did patients with other genotypes. Analysis of predictive factors identified IL28B SNP, rapid viral response, and transient response to previous therapy as significant independent predictors of SVR after triple therapy.

Telaprevir: An NS3/4A Protease Inhibitor for the Treatment of Chronic Hepatitis C

To review the use of telaprevir for the treatment of chronic hepatitis C. Clinical studies were identified through MEDLINE (1966-January 2011), bibliographies of articles, clinicaltrials.gov, and fda.gov, using key words VX-950, telaprevir, and chronic hepatitis C. Phase 1, 2, and 3 human and animal studies describing the pharmacology, pharmacokinetics, efficacy, and safety of telaprevir were identified. Additional articles were identified from the bibliographies of articles retrieved through MEDLINE. Telaprevir is an NS3/4A protease inhibitor under investigation for the treatment of chronic hepatitis C virus (HCV) with pegylated interferon and ribavirin. Telaprevir competes with viral peptide substrates for the active site of NS3 and inhibits NS3-NS4A protease activity. Telaprevir has activity against HCV genotype 1 infection in vitro and in vivo, but monotherapy results in rapid viral resistance. In 3 Phase 2 and 3 Phase 3 randomized placebo-controlled trials, 12 weeks of telaprevir, along with varying durations of ribavirin treatment, induced higher sustained virologic response (SVR) compared with ribavirin alone. SVR was approximately 70% in treatment-naïve patients, 50-60% for patients in whom SVR had not occurred with prior ribavirin treatment, and 40-45% of those who received ribavirin alone. There was a high incidence of maculopapular rash (52% in 1 trial) and anemia (27% in 1 trial) in telaprevir-treated patients. The average dropout rate in Phase 3 trials as a result of adverse effects was 13%. Twelve weeks of telaprevir with concomitant ribavirin treatment increases SVR for treatment-naïve and non-naïve patients with genotype 1 chronic HCV compared to 48 weeks of ribavirin treatment. Telaprevir may shorten the length of ribavirin therapy for some patients with extended rapid viral response, but viral mutations, adverse effects, and a high dropout rate may reduce the SVR seen in clinical practice.

A single centre experience of short course treatment for chronic hepatitis c genotype 2/3 infection in patients with rapid viral response

IntroductionThere is increasing incidence of chronic hepatitis C in Wales with estimated 12 000 individuals infected with the virus giving a prevalence of 0.4% of the population. Welsh BBV Action...

IL28B polymorphisms predict reduction of HCV RNA from the first day of therapy in chronic hepatitis C

Single nucleotide polymorphisms (SNPs) associated with IL28B influence the outcome of peginterferon-α/ribavirin therapy of chronic hepatitis C virus (HCV) infection. We analyzed the kinetics of HCV RNA during therapy as a function of IL28B SNPs. IL28B SNPs rs8099917, rs12979860, and rs12980275 were genotyped in 242 HCV treatment-naïve Caucasian patients (67% genotype 1, 28% genotype 2 or 3) receiving peginterferon-α2a (180 μg weekly) and ribavirin (1000-1200 mg daily) with serial HCV-RNA quantifications. Associations between IL28B polymorphisms and early viral kinetics were assessed, accounting for relevant covariates. In the multivariate analyses for genotype 1 patients, the T allele of rs12979860 (T(rs12979860)) was an independent risk factor for a less pronounced first phase HCV RNA decline (log(10) 0.89IU/ml among T carriers vs. 2.06 among others, adjusted p < 0.001) and lower rapid (15% vs. 38%, adjusted p = 0.007) and sustained viral response rates (48% vs. 66%, adjusted p < 0.001). In univariate analyses, T(rs12979860) was also associated with a reduced second phase decline (p = 0.002), but this association was no longer significant after adjustment for the first phase decline (adjusted p = 0.8). In genotype 2/3 patients, T(rs12979860) was associated with a reduced first phase decline (adjusted p = 0.04), but not with a second phase decline. Polymorphisms in IL28B are strongly associated with the first phase viral decline during peginterferon-α/ribavirin therapy of chronic HCV infection, irrespective of HCV genotype.

Réactivation d’une tuberculose sous bithérapie interféron-pégylé et ribavirine pour une hépatite chronique C

Hepatitis C viral infection can be associated with other infectious diseases including viral and bacterial infections such as tuberculosis. Mycobacterium tuberculosis infection may be latent for many years and revealed during an immunodeficiency state. The responsibility of antiviral treatment in the reactivation of tuberculosis is controversial. We report two cases of tuberculous reactivation during bitherapy with pegylated interferon and ribavirin for chronic hepatitis C. A rapid viral response was obtained in both cases. Tuberculous reactivation occurred at 12 and 13 weeks of antiviral treatment, respectively. Tuberculosis involved urinary tract in one patient and lymph nodes in the other. Antituberculous treatment was given and antiviral treatment maintained. The outcome of tuberculosis was favourable and a sustained viral response was obtained for both patients.

OP12 UK experience of treatment of chronic viral hepatitis C in children and adolescents: predictors of viral response and quality of life

AimThe aim of this study was to review efficacy, tolerability and quality of life (QoL) in children with chronic hepatitis C (HCV) treated with pegylated interferon (PEG-IFN) alfa2a and ribavirin...

A case of gynecomastia due to entecavir

Hepatitis B is an important health problem all over the world as well as in our country. Entecavir is a nucleoside analog used in the treatment of chronic hepatitis B. We present a case of a 55-year-old male patient who developed unilateral gynecomastia while under treatment with entecavir. Physical examination was unremarkable except for minimal hepatomegaly. Laboratory examination revealed: HbsAg: positive, HBeAg: negative, anti-HBe: positive, HBV DNA: 800,000 copies/ml, total anti-HDV: negative, and alanine aminotransferase: 105 U/L (normal range: 0-41). The treatment was started with pegylated interferon. During the follow-up, transaminases did not regress and HBV DNA was found to still be highly positive at the sixth month evaluation. Pegylated interferon treatment was stopped and entecavir was started at a dose of 0.5 mg/day. Six months after the initiation of entecavir treatment, the patient presented with a painful swelling in the right breast. On physical examination, there was painful gynecomastia on the right side, which was confirmed with mammography and ultrasound of the breast tissue. The patient was not taking any drug that may have caused gynecomastia. Hormonal status of the patient was normal. Laboratory values were normal. We considered that this unilateral gynecomastia might be an adverse effect of entecavir. Since the patient had a rapid viral and biochemical response to entecavir, the drug was continued under close follow-up and there was no further progression of the gynecomastia.

OL-003 The clinical features in HIV/AIDS complicated with cytomegalovirus infection

in all genotypes (~30% in African Americans). Alinia (nitazoxanide[NTZ]), an interferon inducer may increase SVR in combination with PegIFN and RBV. Very rapid virologic response (VRVR) defined as undetectable HCVRNA 14 days after initiation of combination therapy may predict even higher SVR rates. We assessed NTZ in combination with high-dose RBV and PegIFN alfa-2a in Hepatitis C treatment. Methods: Prospective, open-label, pilot study of naive patients with chronic hepatitis C GT1. 33 patients were enrolled. Exclusions: uncontrolled diabetes mellitus, decompensated cirrhosis etc. Patients received NTZ 500mg bid for first 2 weeks; RBV 800mg in AM and 600mg at night added to NTZ for next 2 weeks; subcutaneous PegIFN alfa-2a 180mcg weekly added to RBV and NTZ at the same dose (triple-regimen) for next 12 weeks. Patients who achieved EVR continued PegIFN alfa-2a and RBV for the next 36 weeks at the same dose. VRVR, Rapid Viral Response (RVR), Early Viral response (EVR), End Treament Viral Response (ETR), and Sustained Viral Response (SVR) were assessed (COBAS TaqMan HCV Test v2.0, Roche Diagnostics). Results: Overall SVR 66.7% (22/33). Demographics: Caucasian (n = 16, 48.5%), Hispanic (n = 6, 18.2%), AfricanAmerican (n = 5, 15.1%), and Asian (n = 6, 18.2%). Mean BMI 27.9; mean HCVRNA-600,000 IU/ml; fibrosis scoreF2 (48.5%). Growth factors were used to minimize dose reductions. Adverse effects (AE): skin rash (27.3%); neutropenia (51.5%); thrombocytopenia (39.4%); anemia (48.5%); 6.1% discontinued treatment due to AE. None had dose reductions. Conclusion: This regimen of NTZ, high-dose RBV and PegIFN alfa-2a enhances RVR over historical controls and offers an improved SVR rate of 66.7% compared to 40.9% SVR rate in GT1 from the recent IDEAL Study.

Individualisation of antiviral therapy for chronic hepatitis C

The combination of pegylated-interferon (PEG-IFN)/ribavirin is currently the standard of care antiviral treatment for chronic hepatitis C (CHC), but optimal results require an individual approach. Key issues are to deliver doses that confer optimal antiviral efficacy against hepatitis C virus (HCV) for a time sufficient to minimise relapse. Viral monitoring during therapy guides the subsequent treatment course, particularly HCV RNA results at 4 weeks (rapid viral response [RVR]) and 12 weeks (complete early viral response [cEVR]). There is strong evidence that for most patients with genotypes 2 or 3 HCV infection, RVR allows truncation of treatment to 16 weeks, provided ribavirin dose is weight-based. However, those patients with cirrhosis, insulin resistance/diabetes or older than 50 years need 6-12 months treatment. For "difficult-to-treat" CHC (genotypes 1 and 4), RVR is infrequent (approximately 15% in European studies), but allows treatment to be truncated from 48 to 24 weeks. Without RVR, there is some evidence that longer treatment (72 weeks) improves sustained viral response (SVR). However, "induction dosing" first 12 weeks of PEG-IFN clearly does not improve SVR. To prevent dose reductions and complete therapy, it is critical to detect and treat depression and other disabling side-effects, including judicious use of growth factors for severe anemia or neutropenia and possibly, thrombocytopenia. Another potentially important aspect may be attempts to counter central obesity and insulin resistance, which confer suboptimal antiviral response with any HCV genotype. Treatment partnerships with specialist nurses, psychological therapists and other healthcare workers are also essential for optimal individual management of patients with CHC.

Ribavirin dosage in patients with HCV genotypes 2 and 3 who completed short therapy with peg‐interferon α‐2b and ribavirin

Aliment Pharmacol Ther 31, 1346–1353SummaryBackground The optimal dose of ribavirin to be used in combination with Peg‐IFN in patients with HCV genotypes 2 and 3 undergoing short treatment has not been established.Aim To explore the relationship between starting ribavirin doses, expressed as mg/kg body weight and both rapid viral response at treatment week 4 (RVR) and sustained virological response (SVR) in patients treated for 12–14 weeks with peg‐interferon α‐2b and ribavirin.Methods A post hoc analysis of data collected from two multicenter clinical trials was performed. Multiple regression analyses were employed to identify independent baseline and on‐treatment predictors of RVR and SVR. For each dose of ribavirin, the empirical estimated probability of response was computed and the continuous exposure index was dichotomized by using a recursive partitioning and amalgamation method.Results A nonlinear relationship was ascertained between ribavirin dose and RVR, but not SVR. A dose of 15.2 mg/kg was selected as the best splitting value for discriminating RVR vs. non‐RVR. Regression analysis identified low baseline viraemia, genotype 2 and high ribavirin dose as independent prognostic factors for RVR. The likelihood of an SVR was not correlated with baseline ribavirin dose, but was independently predicted by adherence to the full dose throughout treatment and normal platelet counts.Conclusions Starting high ribavirin doses appears capable of increasing the rate of RVR in patients with HCV genotypes 2 and 3 undergoing short treatment. Maintenance of the full planned dose throughout treatment is essential for achieving optimal SVR rates.

New anti HCV drugs in the pipeline

Several novel therapeutic approaches are currently in the pipeline for HCV treatment. They include new target host immune system as novel interferon, toll-like receptor agonists, therapeutic vaccines or interleukins, new target cell replication drug as ribavirin analogues, cyclophilin inhibitors, alpha glucosidase inhibitors, dephosphorylationinhibitors of eukaryotic initiation factors 2alpha, antisense molecule, entry inhibitors and specifically targeted antiviral therapy (STAT-C) such as viral enzyme inhibitor ( protease and polymerase). Several STAT-C molecules are currently in development and will soon be at hand and will offer new treatment opportunities to patients infected with hepatitis C. Promising results leading to more than 70% of sustained virological response in genotype 1 naive patients have been reported with two proteases inhibitors (telaprevir and boceprevir) in combination with pegylated interferon and ribavirin that are currently in phase III. These studies also demonstrated the potential to shorten treatment duration in those with a rapid viral response and the realistic hope for retreatment (40 and 75%) in previous non responders or relapsers to interferon based therapies. In addition there is indication that STAT-C drugs may help to overcome negative host factors that have historically been associated with poor response rates (such as ethnicity, insulin resistance, steatosis and cirrhosis). However these trials also emphasize the limitations of protease inhibitors and viral resistance data have provided important new lessons for small molecule drug development. In the near feature, it is likely that IFN-based therapy plus ribavirin will remain the backbone of the treatment of chronic hepatitis C. PEG-IFN and ribavirin are needed in order to prevent HCV resistance to STAT-C drugs and subsequently increase SVR. Genotypic and phenotypic resistance tests will also enter the therapeutic arena. Once several STAT-C agents without cross resistance become available, treatment strategies will include a combination of several drugs with different mechanisms of action (protease inhibitors and polymerase inhibitors) that could hopefully results in IFN and/or ribavirin sparing regimen. The first dual -- combination clinical trial with oral antiviral is still ongoing. Patients receiving this combination for 14 days had undetectable HCV RNA in 63% of naive genotype1 patients. This early success has moved IFN-free regimen a step closer to reality for patients. In the future, there might be combinations of antivirals having additive potency, lacking cross resistance and with a good safety profile.

PTU-071 Frequency and outcomes associated with rapid viral response in individuals on pegylated interferon and ribavirin therapy: Abstract PTU-071

Introduction Studies have shown that attaining a rapid viral response (RVR) (PCR negative after 4 weeks of interferon and ribavirin therapy) is emerging as a robust predictor of sustained viral response (SVR) to treatment. We started routinely measuring HCV PCR after 4 weeks of treatment in April 2007. The aim of this study was to evaluate the frequency and outcomes associated with RVR in clinical practice. Methods A prospective study was carried out on all individuals who had received interferon and ribavirin therapy in our centre between April 2007 and November 2009. Results A total of 164 individuals were included in the study. 111 (67.7%) were male. The age range was 19 to 77 with a mean of 43.8 years. 67 (40.8%) were genotype 1, 7 (4.2%) genotype 2, 88 (53.6%) genotype 3, and 2 (1.2%) genotype 4. At end week 4, 80/164 (48.7%) had a RVR, of these 22% were genotype 1/4 and 67.7% were 2/3. Of the individuals who did not achieve a RVR, 49 (29.9%) had more than a 2-log drop in viral load, 28 (17%) had less than a 2-log drop and 7 (4.2%) stopped treatment before 4 weeks. 36 individuals are still in treatment. In 128 cases where treatment has ended 75% (96/128) completed treatment. The following analysis focuses on the 96 individuals who are 6 months post treatment. Of the 39 had achieved an RVR (6 genotype 1/4. 33 genotype 2/3), three stopped treatment early (between 4 and 12 weeks) and 35 (97.2%) who subsequently completed treatment achieved a SVR. 21 (84%) who achieved more than a 2-log drop at 4 weeks and completed treatment had SVR and 3 (42.8%) who had less than a 2-log drop had SVR (Abstract 071). Conclusion This study shows that 48.7% of individuals achieved a RVR. The frequency of RVR was significantly altered by genotype. This study confirms that the result of viral load at 4 weeks is very predictive of an SVR if individuals adhere to treatment, with 97.2% of individuals with RVR who completed treatment achieving a SVR. The numbers in this study are small however the results can be used to motivate individuals with RVR or more than a 2 log drop in viral load at 4 weeks to complete their full course of treatment.

PTU-069 Predictors of hepatitis C treatment outcome in genotype 1 patients in a “real world” setting

<h3>Introduction</h3> Many factors affect treatment outcomes in Hepatitis C genotype 1 patients, some of which may differentiate between those achieving sustained viral response (SVR) and those who don9t. Several variables were studied in unselected patients to look at predictive factors for achieving SVR. <h3>Methods</h3> Medical records of 438 patients treated with PEG-IFN α-2b and Ribavirin from 20 UK centres were studied to better understand factors predicting successful treatment outcome in the “real world” outside clinical trials. Data included patient demographics, SVR rates, early viral response (EVR), rapid viral response (RVR), methadone and other medication use and lab assay data. This study was supported by Schering-Plough. <h3>Results</h3> HCV was contracted from injection drug use (61%), blood/blood products (13%) or other source (26%). 55% (243/438) of patients achieved SVR. As expected, male sex, high viral load and cirrhosis were all associated with failure to achieve SVR. 78% (341/438) had a liver biopsy prior to treatment, 12% were cirrhotic. The use of methadone / buprenorphine (65/438) or antidepressants (102/438) did not affect SVR negatively. EPO and GCSF were used in a small number of cases (2%). Higher doses and longer duration use was associated with greater chance of achieving SVR. Younger age (40 vs 46 years, p&lt;0.001) and starting treatment sooner (28 vs 40 months, SVR vs non-SVR, P&lt;0.05) were important factors in achieving SVR. ALT level at baseline was significantly higher in patients achieving SVR (p&lt;0.05). Early normalisation of ALT (week 4) was significantly associated with achieving SVR (p&lt;0.001). GGT levels were significantly higher in patients not achieving SVR (p&lt;0.05). 130 patients had an early viral response. These were divided into two groups – EVR with HCV RNA undetectable (EVR-U, n=73), and those that had &gt;2 log drop in HCV RNA but RNA still detectable at 12 weeks (EVR-D, n=57). EVR-U patients were more likely to achieve SVR when compared to EVR-D patients (p&lt;0.001). 18 patients had a rapid viral response (treatment week 4) with 89% achieving SVR. <h3>Conclusion</h3> Treatment outcomes in UK real world patients mirror results of registration trials, despite treatment of significant numbers on opiate substitutes and antidepressants. Early normalisation of ALT on treatment strongly predicted achieving SVR and may be useful in encouraging adherence. Interestingly, a high GGT appears to be associated with a poorer outcome.