Role of Rapid Virological Response in Prediction in HCV Patients
Role of Rapid Virological Response in Prediction in HCV Patients
Summary: The objective of the study was to evaluate the role of rapid virological response (RVR) in predicting sustained virological response (SVR) rates to hepatitis C virus (HCV) therapy. 65 HIV / HCV co-infected patients commenced HCV treatment per protocol. HIV / HCV patients with a mean CD4 count of 502 were treated for 24-48 weeks depending on genotype. Virological response was assessed at weeks 4 (RVR), 12 [early virological response (EVR)], 24, at end of treatment (EOTR) and 24 weeks post-completion of treatment (SVR). Primary end-point was defined as undetectable HCV RNA at 24 weeks post-treatment completion. Fifty-five per cent of co-infected patients were on highly active anti-retroviral therapy. A majority of patient group were male. 60% of HIV / HCV patients achieved SVR (35% genotype 1 / 4; 77% genotype 2 / 3). 24 HIV / HCV patients achieved undetectable HCV levels compared with baseline by week 4. The positive predictive value (PPV) of RVR at week 4 for subsequent SVR in HIV-HCV co-infected patients was 100%; the negative predictive value (NPV) was 57%. Significant variables associated with SVR were: (i) lower median pre-treatment HCV viral load, (ii) genotype 2 / 3 disease and (iii) achievement of RVR. Independent variables associated with RVR were low pre-treatment HCV viral load and genotype 2 / 3 disease. Achievement of RVR, a negative HCV-PCR, at week 4 of treatment is predictive of SVR in this cohort of patients. This may be used to guide optimal treatment duration in patient groups. More significantly, the data serve to highlight the subgroup of patients who, on achieving RVR, should be actively supported to complete HCV treatment with full dose therapy, especially patients co-infected with G2 / 3 disease for whom 6 months' full dose therapy may be sufficient to obtain a SVR.
With common routes of transmission, chronic hepatitis C infection is frequently encountered in the setting of HIV infection. Overall prevalence of hepatitis C virus (HCV) and HIV co-infection rates approximate 30-40%; however, in intravenous drug users, much higher rates of co-infection prevail. End-stage liver disease in the HCV / HIV co-infected population remains a leading cause of morbidity and mortality. Since the advent of highly active anti-retroviral therapy (HAART), energies have focussed on improving treatment outcomes for chronic HCV in HIV patients.
There is extensive evidence in support of both the efficacy and safety of combination pegylated interferon and ribavirin, for both HCV mono and HIV / HCV co-infected patients. Quoted sustained viral response (SVR) rates range from 27% to 44% in co-infected studies. Until very recently, the standard recommended therapy consisted of 48 weeks of combination HCV therapy for all HIV patients irrespective of genotype.
There is growing support now for individualizing the treatment duration of chronic HCV in co-infected patients similar to that employed in mono-infected groups, namely a shorter duration of HCV therapy in specific subgroups such as genotype 2 disease or genotype 3 with low pre-treatment viral load. With respect to shortening duration of HCV therapy, this group previously reported successful outcomes when employing 24 weeks of HCV therapy in HIV / HCV co-infected patients with genotype 2 / 3 disease with use of weight-based ribavirin and maintenance of full doses of HCV therapies.
The role for monitoring early viral kinetic response has been reported for the management of HCV mono-infected individuals. An early stop rule exists for those failing to achieve undetectable HCV RNA levels by week 12 of treatment. More recent efforts in this patient cohort have focussed on use of week 4 viral response to predict ultimate primary outcome and thus further enable individualization of treatment duration.
The application of the guidelines used for HCV mono-infected patients to co-infected patients is hampered by evidence suggesting slower HCV kinetic response in HCV / HIV patients. The Apricot study group and Carrat et al. concluded that SVR was highly unlikely in co-infected patients failing to achieve early virological response (EVR). There is considerable interest in validating the utility of HCV viral kinetics at earlier time-points to predict primary outcome in co-infected patients, thus identifying those for whom duration of HCV therapy may be shortened.
In this study, we evaluated the role of rapid virological response (RVR) in predicting SVR in HCV / HIV co-infected patients treated with combination pegylated interferon and ribavirin.
Summary: The objective of the study was to evaluate the role of rapid virological response (RVR) in predicting sustained virological response (SVR) rates to hepatitis C virus (HCV) therapy. 65 HIV / HCV co-infected patients commenced HCV treatment per protocol. HIV / HCV patients with a mean CD4 count of 502 were treated for 24-48 weeks depending on genotype. Virological response was assessed at weeks 4 (RVR), 12 [early virological response (EVR)], 24, at end of treatment (EOTR) and 24 weeks post-completion of treatment (SVR). Primary end-point was defined as undetectable HCV RNA at 24 weeks post-treatment completion. Fifty-five per cent of co-infected patients were on highly active anti-retroviral therapy. A majority of patient group were male. 60% of HIV / HCV patients achieved SVR (35% genotype 1 / 4; 77% genotype 2 / 3). 24 HIV / HCV patients achieved undetectable HCV levels compared with baseline by week 4. The positive predictive value (PPV) of RVR at week 4 for subsequent SVR in HIV-HCV co-infected patients was 100%; the negative predictive value (NPV) was 57%. Significant variables associated with SVR were: (i) lower median pre-treatment HCV viral load, (ii) genotype 2 / 3 disease and (iii) achievement of RVR. Independent variables associated with RVR were low pre-treatment HCV viral load and genotype 2 / 3 disease. Achievement of RVR, a negative HCV-PCR, at week 4 of treatment is predictive of SVR in this cohort of patients. This may be used to guide optimal treatment duration in patient groups. More significantly, the data serve to highlight the subgroup of patients who, on achieving RVR, should be actively supported to complete HCV treatment with full dose therapy, especially patients co-infected with G2 / 3 disease for whom 6 months' full dose therapy may be sufficient to obtain a SVR.
With common routes of transmission, chronic hepatitis C infection is frequently encountered in the setting of HIV infection. Overall prevalence of hepatitis C virus (HCV) and HIV co-infection rates approximate 30-40%; however, in intravenous drug users, much higher rates of co-infection prevail. End-stage liver disease in the HCV / HIV co-infected population remains a leading cause of morbidity and mortality. Since the advent of highly active anti-retroviral therapy (HAART), energies have focussed on improving treatment outcomes for chronic HCV in HIV patients.
There is extensive evidence in support of both the efficacy and safety of combination pegylated interferon and ribavirin, for both HCV mono and HIV / HCV co-infected patients. Quoted sustained viral response (SVR) rates range from 27% to 44% in co-infected studies. Until very recently, the standard recommended therapy consisted of 48 weeks of combination HCV therapy for all HIV patients irrespective of genotype.
There is growing support now for individualizing the treatment duration of chronic HCV in co-infected patients similar to that employed in mono-infected groups, namely a shorter duration of HCV therapy in specific subgroups such as genotype 2 disease or genotype 3 with low pre-treatment viral load. With respect to shortening duration of HCV therapy, this group previously reported successful outcomes when employing 24 weeks of HCV therapy in HIV / HCV co-infected patients with genotype 2 / 3 disease with use of weight-based ribavirin and maintenance of full doses of HCV therapies.
The role for monitoring early viral kinetic response has been reported for the management of HCV mono-infected individuals. An early stop rule exists for those failing to achieve undetectable HCV RNA levels by week 12 of treatment. More recent efforts in this patient cohort have focussed on use of week 4 viral response to predict ultimate primary outcome and thus further enable individualization of treatment duration.
The application of the guidelines used for HCV mono-infected patients to co-infected patients is hampered by evidence suggesting slower HCV kinetic response in HCV / HIV patients. The Apricot study group and Carrat et al. concluded that SVR was highly unlikely in co-infected patients failing to achieve early virological response (EVR). There is considerable interest in validating the utility of HCV viral kinetics at earlier time-points to predict primary outcome in co-infected patients, thus identifying those for whom duration of HCV therapy may be shortened.
In this study, we evaluated the role of rapid virological response (RVR) in predicting SVR in HCV / HIV co-infected patients treated with combination pegylated interferon and ribavirin.
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