Sofosbuvir and Ribavirin in HCV Genotypes 2 and 3

Zeuzem, Stefan; Dusheiko, Geoffrey; Salupere, Riina; Mangia, Alessandra; Flisiak, Robert; Hyland, Robert H.; Illeperuma, Ari; Svarovskaia, Evguenia S.; Brainard, Diana M.; Symonds, William T.; Subramanian, G. Mani; McHutchison, John G.; Weiland, Ola; Reesink, H. W.; Ferenci, Péter; Hézode, Christophe; Esteban, Rafael

doi:10.1056/nejmoa1316145

Cited by 746 publications

(790 citation statements)

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“…According to treatment experience, SVR rate was 97% (29/30) in treatment-naive noncirrhotic patients, 100% (2/2) in treatment-naive cirrhotic patients, 91% (30/33) in treatment-experienced noncirrhotic patients, and 88% (7/8) in treatment-experienced cirrhotic patients. 36 The BOSON study has reinforced these results. In a cohort of 32 treatment-experienced GT-2 cirrhotic patients, SVR rates were 87% (13/15) after 16 weeks of SOF/RBV therapy and 100% (17/17) after 24 weeks.…”

Section: Genotypesmentioning

confidence: 78%

“…35 In the VALENCE trial, the SVR rates were 91% and 68% among those without and those with cirrhosis, respectively. 36 These data show that even 24 weeks of therapy with SOF/RBV is suboptimal in patients with liver cirrhosis.…”

Section: Genotypementioning

confidence: 85%

“…The SVR rate with 24 weeks of therapy for GT-3 in treatment-naive HCV patients was 94%, while that for 12 weeks of therapy was only 27%. 36 Treatment-experienced genotype 3: The FUSION trial was designed to assess the benefit of extending duration of treatment in patients who had failed previous therapy. This phase-3 trial compared SOF/RBV for 12 weeks with SOF/RBV for 16 weeks in treatment-experienced patients with GT-2 or 3 HCV infection.…”

Section: Genotypementioning

confidence: 99%

“…This study has established the paradigm that GT-3 patients need 24 weeks of SOF/RBV. 36 Genotype 3 with cirrhosis: The SVR rates of 12-week therapy with SOF and RBV therapy in HCV-related cirrhosis in the FISSION and POSITRON trials were 47% and 21%, respectively. 19,35 In the FUSION trial, the SVR rate in cirrhotics with 12-week therapy was 61%, while that with 16-week therapy was 85%.…”

Section: Genotypementioning

confidence: 99%

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Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Puri

Saraswat

Dhiman

et al. 2016

Journal of Clinical and Experimental Hepatology

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India contributes significantly to the global burden of HCV. While the nucleoside NS5B inhibitor sofosbuvir became available in the Indian market in March 2015, the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only recently become available in the India. The introduction of these DAA in India at a relatively affordable price has led to great optimism about prospects of cure for these patients as not only will they provide higher efficacy, but combination DAAs as all-oral regimen will result in lower side effects than were seen with pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs has necessitated revision of INASL guidelines for the treatment of HCV published in 2015. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. The availability of combination DAA therapy has simplified therapy of HCV with decreased reliance of evaluation for monitoring viral kinetics or drug related side effects. ( J CLIN EXP HEPATOL 2016;6:119-145) T here have been revolutionary changes in the management of chronic hepatitis C (CH-C) over the last few years. Pegylated interferon alfa (Peg-IFNa) plus ribavirin (RBV) therapy, which till the recent past was the standard of care, has been eclipsed by the arrival of newer directly acting antiviral agents (DAAs). Not only do the DAAs have better efficacy, they are also associated with lower side effects, have better tolerability, a shorter duration of therapy, and have simpler administration.In the recent guidelines issued by the American Association for the study of Liver Diseases (AASLD), in collaboration with the Infectious Diseases Society of America 1 and the European Association for Study of the Liver z (EASL), 2 the role of Peg-IFNa/RBV therapy in the management of HCV has been relegated to second-line, backup status. These newer guidelines, however, cannot be implemented in India as many of the recommended drugs are yet to be marketed in India. Other considerations for the treatment of HCV in India are a predominance of

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Section: Genotypesmentioning

confidence: 78%

Section: Genotypementioning

confidence: 85%

Section: Genotypementioning

confidence: 99%

Section: Genotypementioning

confidence: 99%

See 2 more Smart Citations

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Puri

Saraswat

Dhiman

et al. 2016

Journal of Clinical and Experimental Hepatology

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“…The pangenotypic NS5B HCV inhibitor sofosbuvir (SOF) has demonstrated high efficacy in patients infected with HCV in combination with ledipasvir (LDV) for genotype (GT) 1, 2, 4, 5, and 62, 3, 4, 5, 6, 7 and in combination with ribavirin (RBV) with or without pegylated interferon for GT3 HCV 8, 9. SOF exhibits a high barrier to resistance in vivo.…”

mentioning

confidence: 99%

The emergence of NS5B resistance associated substitution S282T after sofosbuvir‐based treatment

Gane

Métivier

Nahass³

et al. 2017

Hepatology Communications

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S282T in NS5B is the primary amino acid substitution associated with resistance to sofosbuvir (SOF) but has rarely been detected in patients treated with a SOF‐based regimen. Here, the emergence and fitness of the S282T substitution in virologic failure patients administered SOF‐based regimens across the SOF and ledipasvir (LDV)/SOF phase 2 and 3 programs was evaluated. Plasma samples collected at baseline and at virologic failure were amplified and deep sequenced (1% cutoff). To date, over 12,000 patients have been treated in SOF or LDV/SOF phase 2 and 3 studies. Of these, deep sequencing was available at baseline in 8598 patients (62.4% genotype [GT] 1, 10.7% GT2, 20.9% GT3, and 6.0% GT4‐6) and at virologic failure in 901 patients. In the 8598 patients, no S282T substitution was detected at baseline; at virologic failure, 10 of the 901 (1%) patients had S282T detected. The SOF‐based regimen associated with treatment‐emergent S282T was SOF monotherapy in two patients, retreatment with LDV/SOF in prior LDV/SOF failures in three patients, LDV/SOF for 8 weeks in 1 GT1 patient, LDV/SOF for 12 weeks in 1 patient each with GT3, GT4, and GT5, and LDV/SOF + ribavirin for 12 weeks in 1 GT6 patient. Nine of 10 patients with emergent S282T received an SOF‐based retreatment regimen, eight of whom achieved sustained virologic response 12 weeks after treatment and one of whom failed retreatment. Conclusion: The emergence of S282T substitution was rare in patients who fail SOF‐based regimens. Successful retreatment of prior SOF failure patients is possible in the presence of S282T substitution with SOF in combination with various direct‐acting antiviral agents. (Hepatology Communications 2017;1:538–549)

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Sofosbuvir and Ribavirin for Hepatitis C in Patients With HIV Coinfection

Sulkowski

Naggie

Lalezari

et al. 2014

JAMA

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Importance Treatment of hepatitis C virus (HCV) infection in HIV-1 co-infected patients has been limited due to the use of interferon and drug interactions with antiretroviral therapies (ART). Objective To determine the rates of HCV eradication (sustained virologic response, SVR) and adverse events in HCV/HIV-1 co-infected patients receiving sofosbuvir and ribavirin treatment. Design Multicenter, open-label, non-randomized, uncontrolled phase 3 trial (PHOTON-1) conducted in the United States and Puerto Rico from August 2012 until November 2013 evaluating treatment with sofosbuvir and ribavirin. Setting Thirty-four academic, private practice, and community health centers with a median of 6 patients (range 1–17) enrolled at each site. Participants Patients with HCV genotypes 1, 2, or 3 and concurrent HIV-1 were eligible. Patients were required to be receiving antiretroviral treatment with an HIV-1 RNA <50 copies/mL and a CD4 T-cell count of >200 cells/mm3 or have untreated HIV-1infection with a CD4 T-cell count of >500 cells/mm3. In total, 223 participants (114 treatment-naïve participants with HCV genotype 1, 68 treatment-naïve participants with HCV genotype 2 or 3, and 41 peginterferon/ribavirin treatment-experienced participants with HCV genotype 2 or 3) were enrolled. Interventions Participants received sofosbuvir (400 mg) and weight-based ribavirin for 12 weeks (for treatment-naïve patients with HCV genotype 2 or 3) or for 24 weeks (for treatment-naïve patients with HCV genotype 1 or treatment-experienced patients with HCV genotype 2 or 3). Main Outcome and Measure The primary study outcome was proportion of patients with SVR (serum HCV <25 copies/mL) 12 weeks after cessation of HCV therapy (SVR12). Results Among treatment-naïve participants, SVR12 rates were 76% (95% confidence interval [CI], 67–84) for genotype 1 infection, 88% (95% CI, 70–98) for genotype 2 infection, and 67% (95% CI, 51–80) for genotype 3 infection. Among treatment-experienced participants, SVR12 was 92% (95% CI, 73–99) for genotype 2 infection and 94% (95% CI, 71–100) for genotype 3 infection. The most common adverse events were fatigue, insomnia, headache, and nausea. Seven patients (3%) discontinued HCV treatment due to adverse events. No adverse effect on HIV disease or its treatment was observed. Conclusions and Relevance In this open-label, nonrandomized, uncontrolled phase 3 study, HIV-1-infected patients coinfected with HCV genotype 1, 2, or 3 who received the oral, interferon-free combination of sofosbuvir and ribavirin for 12 or 24 weeks had high rates of sustained virologic response 12 weeks after cessation of therapy. Further studies of this oral regimen in diverse populations of coinfected patients are warranted. Trial Registration clinicaltrials.gov Identifier: NCT01667731

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Sofosbuvir and Ribavirin in HCV Genotypes 2 and 3

Abstract: Therapy with sofosbuvir-ribavirin for 12 weeks in patients with HCV genotype 2 infection and for 24 weeks in patients with HCV genotype 3 infection resulted in high rates of sustained virologic response. (Funded by Gilead Sciences; VALENCE ClinicalTrials.gov number, NCT01682720.).

Cited by 746 publications

References 16 publications

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

The emergence of NS5B resistance associated substitution S282T after sofosbuvir‐based treatment

Sofosbuvir and Ribavirin for Hepatitis C in Patients With HIV Coinfection

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