Dataset Information

Ribavirin dose management in HCV patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin.

ABSTRACT:

Background & aims

Some individuals with hepatitis C virus infection treated with direct-acting antivirals require ribavirin to maximize sustained virological response rates. We describe the clinical management of ribavirin dosing in hepatitis C virus-infected patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin.

Methods

We performed a post hoc analysis of patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin for 12 or 24 weeks in six phase 3 trials. Multivariate stepwise logistic regression models assessed predictors associated with ribavirin dose adjustments and with developing anaemia.

Results

Of 1548 patients, 100 (6.5%) modified ribavirin dose due to haemoglobin declines, of which 99% achieved sustained virological response at 12 weeks post-treatment. Median time to first ribavirin dose reduction was 37 days. Low baseline haemoglobin was significantly associated with an increased risk of requiring ribavirin dose modification (odds ratio: 0.618 [0.518, 0.738]; P < .001) and developing anaemia (odds ratio: 0.379 [0.243, 0.593]; P < .001).

Conclusions

Ribavirin dose reductions were infrequent, occurred early in treatment, and did not impact sustained virological response at 12 weeks post-treatment. Patients with low baseline haemoglobin should be monitored for on-treatment anaemia.

SUBMITTER: Feld JJ

PROVIDER: S-EPMC6175401 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

Ribavirin dose management in HCV patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin.

Feld Jordan J JJ Bernstein David E DE Younes Ziad Z Vlierberghe Hans Van HV Larsen Lois L Tatsch Fernando F Ferenci Peter P

Liver international : official journal of the International Association for the Study of the Liver 20180314 9

<h4>Background & aims</h4>Some individuals with hepatitis C virus infection treated with direct-acting antivirals require ribavirin to maximize sustained virological response rates. We describe the clinical management of ribavirin dosing in hepatitis C virus-infected patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin.<h4>Methods</h4>We performed a post hoc analysis of patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin for 12 or 24 wee ...[more]

PMID: 29377566

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Project description:ObjectivesAcid-reducing agents (ARAs) and proton-pump inhibitors (PPIs) that increase gastric pH can alter the bioavailability of antiviral drugs, particularly relevant in patients with advanced liver disease caused by chronic hepatitis C virus (HCV) infection seeking therapy. Using integrated data from six phase 3 studies, we report the safety and efficacy of the 3-direct-acting antiviral (DAA) regimen containing ombitasvir (OBV, an NS5A inhibitor), ritonavir-boosted paritaprevir (PTV/r, an NS3/4A protease inhibitor), and dasabuvir (DSV, an NS5B polymerase inhibitor) with or without ribavirin (RBV) for HCV genotype 1 patients taking concomitant ARAs and PPIs.MethodsTreatment-naïve or peginterferon/RBV treatment-experienced patients with or without compensated cirrhosis received OBV/PTV/r and DSV with or without weight-based RBV. Rates of sustained virologic response (SVR), defined as HCV RNA below the lower limit of quantification, 12 weeks post-treatment (SVR12) and safety were evaluated in patients who were receiving concomitant ARAs.ResultsAmong 2,053 patients enrolled and dosed with study drug, 410 (20%) were receiving concomitant ARAs; of these, 308 (15%) were taking concomitant PPIs. Rates of SVR12 were 95.9% (95% confidence interval (CI) 93.5-97.4%) among patients receiving an ARA, and 96.3% (95% CI 95.3-97.2%) in patients not receiving a concomitant ARA. Similarly, among patients receiving a PPI or not, SVR12 was achieved in 95.1% (95% CI 92.1-97.0%) and 96.4% (95% CI 95.5-97.2%), respectively. Response rates were high regardless of treatment regimen (with or without RBV), and among patients receiving a standard or high dose of PPIs. Regarding safety, adverse events and serious adverse events were more frequently reported in patients taking concomitant ARAs, though baseline population differences may have played a role.ConclusionsIn phase 3 trials of OBV/PTV/r plus DSV and RBV in HCV genotype 1-infected patients, SVR12 rates were high regardless of ARA/PPI use or PPI dose. These data support the co-administration of this regimen with ARAs including PPIs.

Project description:The renal function is a key-issue in HIV/HCV co-infected patients, nevertheless, it has not established so far whether HCV treatment with new direct acting agents could impact on estimated glomerular filtration rate (eGFR) variations. In the present work, we examined the real-life data on renal function that have been prospectively collected in the SIMIT compassionate-use program of ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r + DSV) in 144 HIV/HCV genotype 1 co-infected patients. The population was 74% male, 30.5% in CDC stage C, with median age of 52 years (48.0-56.5) and median liver stiffness of 7.8 kPa (6.7-9.2). Median baseline eGFR was 102.0 (90.8-108.1), changing to 99.8 (83.5-104.8) at the end of treatment (EoT), and 100.0 (87.3-105.6) 12 weeks after the EoT (FU12), p<0.0001. No patient had grade 3-4 increase of creatinine. At EoT 60/144 (41.7%) patients had ? 5% reduction in their eGFR, confirmed at FU12 in 39/60 (65.0%) cases. Longer duration of HCV infection (cut-off 12.9 years), lower HCV-RNA viral load (cut-off 1,970,160 IU/ml) and lower platelet count (cut-off 167,000 x106/L) were significantly associated with eGFR decline at logistic analysis (adjOR 2.9, 95%CI 1.0-8.8, p = 0.05; adjOR 3.5, 95%CI 1.2-10.4, p = 0.02; adjOR 2.8, 95%CI 1.1-6.8, p = 0.03, respectively). After repeating the analysis throughout a mixed model, a higher eGFR decline was highlighted in patients concomitantly treated with tenofovir (p = 0.0001), ribavirin (p = 0.0001), or integrase inhibitors (p <0.0001), with longer duration of HIV (p = 0.0002) and HCV infection (p = 0.035), lower baseline HCV RNA (p <0.0001), previous HCV treatment (p<0.0001), and older age (p<0.0001). In conclusion, our study confirms a good renal safety profile of OBV/PTV/r + DSV treatment in HIV/HCV patients, and the median decline of 2 ml/min in eGFR, albeit statistically significant, is of doubtful clinical significance. The role of aging, concomitant therapies and duration of HIV/HCV infection needs to be further investigated.

Dataset Information

Ribavirin dose management in HCV patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin.

Background & aims

Methods

Results

Conclusions

Publications

Ribavirin dose management in HCV patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin.

Similar Datasets

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