TY - JOUR
T1 - Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2)
T2 - A multicentre, open-label, non-randomised, phase 3 study
AU - Molina, Jean Michel
AU - Orkin, Chloe
AU - Iser, David M.
AU - Zamora, Francisco Xavier
AU - Nelson, Mark
AU - Stephan, Christoph
AU - Massetto, Benedetta
AU - Gaggar, Anuj
AU - Ni, Liyun
AU - Svarovskaia, Evguenia
AU - Brainard, Diana
AU - Subramanian, G. Mani
AU - McHutchison, John G.
AU - Puoti, Massimo
AU - Rockstroh, Jürgen K.
N1 - Funding Information:
J-MM has received honoraria for serving on advisory boards from Gilead, Janssen, Merck, ViiV and Bristol-Myers Squibb, and research grants from Merck and Gilead. MP has received personal fees for serving on temporary advisory boards or for participation in non-continuing medical education events, and has received research grants, from Abbvie, Astellas, Bristol-Myers Squibb, Boehringer Ingelheim, Beckman, Janssen, Gilead Sciences, GlaxoSmithKline, MSD, Novartis, Roche, Vertex, and ViiV. CO has received consulting fees or honoraria from Bristol-Myers Squibb, Gilead, Janssen, and MSD. MN has received grants, consulting fees, speakers fees, and support for travel from MSD, Janssen, Gilead, Abbott, Roche, Bristol-Myers Squibb, and ViiV. BM, AG, LN, ES, DB, GMS, and JGMcH are employees of Gilead Sciences. DMI, F-XZ, CS, and JKR declare no competing interests.
Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/3/21
Y1 - 2015/3/21
N2 - Background Although interferon-free regimens are approved for patients co-infected with HIV and genotype-2 or genotype-3 hepatitis C virus (HCV), interferon-based regimens are still an option for those co-infected with HIV and HCV genotypes 1 or 4. These regimens are limited by clinically significant toxic effects and drug interactions with antiretroviral therapy. We aimed to assess the efficacy and safety of an interferon-free, all-oral regimen of sofosbuvir plus ribavirin in patients with HIV and HCV co-infection. Methods We did this open-label, non-randomised, uncontrolled, phase 3 study at 45 sites in seven European countries and Australia. We enrolled patients (aged ≥18 years) co-infected with stable HIV and chronic HCV genotypes 1-4, including those with compensated cirrhosis. Once-daily sofosbuvir (400 mg) plus twice-daily ribavirin (1000 mg in patients with bodyweights <75 kg and 1200 mg in those with weights ≥75 kg) was given for 24 weeks to all patients except treatment-naive patients with genotype-2 HCV, who received a 12-week regimen. The primary efficacy endpoint was sustained virological response 12 weeks after treatment. We did analysis by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01783678. Findings Between Feb 7, 2013, and July 29, 2013, we enrolled 275 eligible patients, of whom 262 (95%) completed treatment; 274 patients were included in the final analysis. Overall rates of sustained virological response 12 weeks after treatment were 85% (95% CI 77-91) in patients with genotype-1 HCV, 88% (69-98) in patients with genotype-2 HCV, 89% (81-94) in patients with genotype-3 HCV, and 84% (66-95) in patients with genotype-4 HCV. Response rates in treatment-naive patients with HCV genotypes 2 or 3 (89% [95% CI 67-99] and 91% [81-97], respectively) were similar to those in treatment-experienced patients infected with those genotypes (83% [36-100] and 86% [73-94], respectively). There was no emergence of sofosbuvir-resistance mutations in patients with HCV viral relapse. Six (2%) patients discontinued treatment because of adverse events. The most common adverse events were fatigue, insomnia, asthenia, and headache. Four (1%) patients had serious adverse events regarded as related to study treatment. Additionally, four (1%) patients receiving antiretroviral treatment had a transient HIV viral breakthrough; however, none required changes in antiretroviral regimen. Interpretation Sofosbuvir and ribavirin provided high rates of sustained virological response after 12 weeks of treatment in treatment-naive and treatment-experienced patients co-infected with HIV and HCV genotypes 1-4. The characteristics of this interferon-free combination regimen make sofosbuvir plus ribavirin a useful treatment option for this patient population. Funding Gilead Sciences.
AB - Background Although interferon-free regimens are approved for patients co-infected with HIV and genotype-2 or genotype-3 hepatitis C virus (HCV), interferon-based regimens are still an option for those co-infected with HIV and HCV genotypes 1 or 4. These regimens are limited by clinically significant toxic effects and drug interactions with antiretroviral therapy. We aimed to assess the efficacy and safety of an interferon-free, all-oral regimen of sofosbuvir plus ribavirin in patients with HIV and HCV co-infection. Methods We did this open-label, non-randomised, uncontrolled, phase 3 study at 45 sites in seven European countries and Australia. We enrolled patients (aged ≥18 years) co-infected with stable HIV and chronic HCV genotypes 1-4, including those with compensated cirrhosis. Once-daily sofosbuvir (400 mg) plus twice-daily ribavirin (1000 mg in patients with bodyweights <75 kg and 1200 mg in those with weights ≥75 kg) was given for 24 weeks to all patients except treatment-naive patients with genotype-2 HCV, who received a 12-week regimen. The primary efficacy endpoint was sustained virological response 12 weeks after treatment. We did analysis by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01783678. Findings Between Feb 7, 2013, and July 29, 2013, we enrolled 275 eligible patients, of whom 262 (95%) completed treatment; 274 patients were included in the final analysis. Overall rates of sustained virological response 12 weeks after treatment were 85% (95% CI 77-91) in patients with genotype-1 HCV, 88% (69-98) in patients with genotype-2 HCV, 89% (81-94) in patients with genotype-3 HCV, and 84% (66-95) in patients with genotype-4 HCV. Response rates in treatment-naive patients with HCV genotypes 2 or 3 (89% [95% CI 67-99] and 91% [81-97], respectively) were similar to those in treatment-experienced patients infected with those genotypes (83% [36-100] and 86% [73-94], respectively). There was no emergence of sofosbuvir-resistance mutations in patients with HCV viral relapse. Six (2%) patients discontinued treatment because of adverse events. The most common adverse events were fatigue, insomnia, asthenia, and headache. Four (1%) patients had serious adverse events regarded as related to study treatment. Additionally, four (1%) patients receiving antiretroviral treatment had a transient HIV viral breakthrough; however, none required changes in antiretroviral regimen. Interpretation Sofosbuvir and ribavirin provided high rates of sustained virological response after 12 weeks of treatment in treatment-naive and treatment-experienced patients co-infected with HIV and HCV genotypes 1-4. The characteristics of this interferon-free combination regimen make sofosbuvir plus ribavirin a useful treatment option for this patient population. Funding Gilead Sciences.
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U2 - 10.1016/S0140-6736(14)62483-1
DO - 10.1016/S0140-6736(14)62483-1
M3 - Article
C2 - 25659285
AN - SCOPUS:84925685148
SN - 0140-6736
VL - 385
SP - 1098
EP - 1106
JO - The Lancet
JF - The Lancet
IS - 9973
ER -