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1.
Am J Gastroenterol ; 116(9): 1924-1928, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465694

RESUMO

INTRODUCTION: We evaluated 8, 12, or 24 weeks of ledipasvir/sofosbuvir in patients with hepatitis C virus and end-stage renal disease undergoing dialysis. METHODS: Primary efficacy end point was sustained virologic response 12 weeks after treatment. Primary safety end point was treatment discontinuation because of adverse events (AEs). RESULTS: Ninety-four percent (89/95) achieved sustained virologic response 12 weeks after treatment. Six patients died during treatment (n = 4) or before study completion (n = 2); no deaths were related to treatment. No patients discontinued treatment because of AEs. Thirteen percent had serious AEs; none were related to treatment. DISCUSSION: Treatment with ledipasvir/sofosbuvir was safe and effective in patients with end-stage renal disease undergoing dialysis.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepatite C/tratamento farmacológico , Falência Renal Crônica/terapia , Sofosbuvir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Esquema de Medicação , Feminino , Fluorenos/administração & dosagem , Hepatite C/complicações , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Sofosbuvir/administração & dosagem , Resposta Viral Sustentada , Resultado do Tratamento
2.
J Am Heart Assoc ; 10(18): e021245, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34482708

RESUMO

Background Biological mechanisms underlying the association of a healthy diet with chronic diseases remain unclear. Targeted proteomics may facilitate the understanding of mechanisms linking diet to chronic diseases. Methods and Results We examined 6360 participants (mean age 50 years; 54% women) in the Framingham Heart Study. The associations between diet and 71 cardiovascular disease (CVD)-related proteins were examined using 3 diet quality scores: the Alternate Healthy Eating Index, the modified Mediterranean-style Diet Score, and the modified Dietary Approaches to Stop Hypertension diet score. A mediation analysis was conducted to examine which proteins mediated the associations of diet with incident CVD and all-cause mortality. Thirty of the 71 proteins were associated with at least 1 diet quality score (P<0.0007) after adjustment for multiple covariates in all study participants and confirmed by an internal validation analysis. Gene ontology analysis identified inflammation-related pathways such as regulation of cell killing and neuroinflammatory response (Bonferroni corrected P<0.05). During a median follow-up of 13 years, we documented 512 deaths and 488 incident CVD events. Higher diet quality scores were associated with lower risk of CVD (P≤0.03) and mortality (P≤0.004). After adjusting for multiple potential confounders, 4 proteins (B2M [beta-2-microglobulin], GDF15 [growth differentiation factor 15], sICAM1 [soluble intercellular adhesion molecule 1], and UCMGP [uncarboxylated matrix Gla-protein]) mediated the association between at least 1 diet quality score and all-cause mortality (median proportion of mediation ranged from 8.6% to 25.9%). We also observed that GDF15 mediated the association of the Alternate Healthy Eating Index with CVD (median proportion of mediation: 8.6%). Conclusions Diet quality is associated with new-onset CVD and mortality and with circulating CVD-related proteins. Several proteins appear to mediate the association of diet with these outcomes.

4.
J Hepatol ; 71(4): 660-665, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31195062

RESUMO

BACKGROUND & AIMS: Although off-label use of sofosbuvir-containing regimens occurs regularly in patients with hepatitis C virus (HCV) infection undergoing dialysis for severe renal impairment or end-stage renal disease (ESRD), these regimens are not licensed for this indication, and there is an absence of dosing recommendations in this population. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir in patients with HCV infection with ESRD undergoing dialysis. METHODS: In this phase II, single-arm study, 59 patients with genotype 1-6 HCV infection with ESRD undergoing hemodialysis or peritoneal dialysis received open-label sofosbuvir/velpatasvir (400 mg/100 mg) once daily for 12 weeks. Patients were HCV treatment naive or treatment experienced without cirrhosis or with compensated cirrhosis. Patients previously treated with any HCV NS5A inhibitor were not eligible. The primary efficacy endpoint was the proportion of patients achieving sustained virologic response (SVR) 12 weeks after discontinuation of treatment (SVR12). The primary safety endpoint was the proportion of patients who discontinued study drug due to adverse events. RESULTS: Overall, 56 of 59 patients achieved SVR12 (95%; 95% CI 86-99%). Of the 3 patients who did not achieve SVR12, 2 patients had virologic relapse determined at post-treatment Week 4 (including 1 who prematurely discontinued study treatment), and 1 patient died from suicide after achieving SVR through post-treatment Week 4. The most common adverse events were headache (17%), fatigue (14%), nausea (14%), and vomiting (14%). Serious adverse events were reported for 11 patients (19%), and all were deemed to be unrelated to sofosbuvir/velpatasvir. CONCLUSIONS: Treatment with sofosbuvir/velpatasvir for 12 weeks was safe and effective in patients with ESRD undergoing dialysis. LAY SUMMARY: Sofosbuvir/velpatasvir is a combination direct-acting antiviral that is approved for treatment of patients with hepatitis C virus (HCV) infection. Despite the lack of dosing recommendations, sofosbuvir-containing regimens (including sofosbuvir/velpatasvir) are frequently used for HCV-infected patients undergoing dialysis. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir for 12 weeks in patients with HCV infection who were undergoing dialysis. Treatment with sofosbuvir/velpatasvir was safe and well tolerated, resulting in a cure rate of 95% in patients with HCV infection and end-stage renal disease. Clinical Trial Number: NCT03036852.


Assuntos
Carbamatos , Hepatite C Crônica , Compostos Heterocíclicos de 4 ou mais Anéis , Falência Renal Crônica , Diálise Renal/métodos , Sofosbuvir , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Carbamatos/administração & dosagem , Carbamatos/efeitos adversos , Combinação de Medicamentos , Monitoramento de Medicamentos/métodos , Feminino , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Cirrose Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Sofosbuvir/administração & dosagem , Sofosbuvir/efeitos adversos , Resposta Viral Sustentada , Resultado do Tratamento
5.
Hepatol Int ; 13(2): 173-179, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30790229

RESUMO

BACKGROUND AND AIMS: In clinical studies, sofosbuvir-velpatasvir has demonstrated high cure rates and favorable tolerability in patients chronically infected with chronic hepatitis C virus (HCV) of any genotype. We evaluated the effectiveness and safety of sofosbuvir-velpatasvir administered with minimal medical monitoring to patients in India. METHODS: At 16 sites in India, 129 adult patients with chronic HCV infection of any genotype initiated 12 weeks of once-daily sofosbuvir-velpatasvir (400-100 mg). Patients with compensated cirrhosis or prior treatment experience could be included in the study. Study drug was dispensed monthly, but there were no on-treatment study assessments. The primary efficacy endpoint was rate of sustained virologic response (HCV RNA < 15 IU/mL) 12 weeks after treatment (SVR12), which was compared to a pre-specified performance goal of 85%. RESULTS: The majority of patients had HCV genotype 3 infection (70%), followed by HCV genotype 1 (22%). The SVR12 rate was 93% (120/129; 95% CI, 87% to 97%) (p = 0.009 compared with the 85% performance goal). Of the nine patients who did not achieve SVR12, 1 experienced virologic failure, 2 relapsed after treatment, 1 withdrew consent after treatment, and 5 were lost to follow-up (1 during and 4 after treatment). Sofosbuvir-velpatasvir was well-tolerated, and no patients discontinued treatment because of an adverse event. The most frequently reported adverse events were headache (3% of patients), upper abdominal pain (2%), and pyrexia (2%). CONCLUSIONS: In this study conducted at multiple sites in India, sofosbuvir-velpatasvir administered without genotype restriction or on-treatment safety assessments was well-tolerated and highly effective.


Assuntos
Carbamatos/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Adulto , Idoso , Carbamatos/efeitos adversos , Combinação de Medicamentos , Monitoramento de Medicamentos , Feminino , Genótipo , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Humanos , Índia , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Recidiva , Sofosbuvir/efeitos adversos , Resultado do Tratamento , Adulto Jovem
6.
Infect Dis (Lond) ; 51(2): 131-139, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30499360

RESUMO

BACKGROUND: In both Russia and Sweden, the dominant hepatitis C virus (HCV) is genotype 1, but around one-third of patients have genotype 3 infection. For such countries, HCV genotype testing is recommended prior to therapy. An effective pangenotypic therapy may potentially eliminate the need for genotyping. In this study, we evaluated the efficacy and safety of sofosbuvir/velpatasvir for 12 weeks in patients from Russia and Sweden. METHODS: In an open-label, single-arm phase-3 study, patients could have HCV genotype 1-6 infection and were treatment-naïve or interferon treatment-experienced. All patients received sofosbuvir/velpatasvir, once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). RESULTS: Of 122 patients screened, 119 were enrolled and treated. Overall, half (50%) were male, 18% had cirrhosis, and 24% had failed prior interferon-based therapy. In total, 66% of patients were infected with HCV genotype 1 (59% 1b and 7% 1a), 6% with genotype 2, and 29% with genotype 3. The overall SVR12 rate was 99% (118/119, 95% confidence interval 95-100%). One treatment-experienced patient infected with HCV genotype 3 experienced virologic relapse after completing treatment. The most common adverse events were headache (16%) and fatigue (7%). Serious adverse events were observed in four patients, but none were related to treatment. No patients discontinued treatment due to adverse events. CONCLUSION: Sofosbuvir/velpatasvir as a pangenotypic treatment for 12 weeks was highly effective in patients from Russia and Sweden infected with HCV genotypes 1, 2, or 3. Sofosbuvir/velpatasvir was safe and well-tolerated. Clinical trial number: ClinicalTrials.gov NCT02722837.


Assuntos
Antivirais/uso terapêutico , Carbamatos/uso terapêutico , Hepatite C/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Sofosbuvir/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/administração & dosagem , Carbamatos/administração & dosagem , Quimioterapia Combinada , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Federação Russa , Sofosbuvir/administração & dosagem , Suécia , Adulto Jovem
7.
Lancet Gastroenterol Hepatol ; 4(2): 127-134, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30555048

RESUMO

BACKGROUND: Treatment with combined sofosbuvir and velpatasvir has resulted in high sustained virological response rates in patients chronically infected with hepatitis C virus (HCV) with genotypes 1-6 in clinical trials and real-world settings, but its efficacy and safety has not been assessed in Asia, a region with diverse HCV genotypes. METHODS: In this single-arm, open-label, phase 3 trial, we recruited patients from 38 sites across China, Thailand, Vietnam, Singapore, and Malaysia, who were chronically infected with HCV genotypes 1-6, and were HCV treatment-naive or treatment-experienced, either without cirrhosis or with compensated cirrhosis. Patients self-administered a combined sofosbuvir (400 mg) and velpatasvir (100 mg) tablet once daily for 12 weeks. The primary efficacy endpoint was sustained virological response, defined as HCV RNA less than 15 IU/mL at 12 weeks after completion of treatment (SVR12), assessed in all patients who received at least one dose of study drug. The primary safety endpoint was the proportion of adverse events leading to premature discontinuation of study drug. This trial is registered with ClinicalTrials.gov, number NCT02671500, and is completed. FINDINGS: Between April 14, 2016, and June 30, 2017, 375 patients were enrolled in the study, of whom 374 completed the full treatment course and one discontinued treatment. Overall, 362 (97% [95% CI 94-98]) of 375 patients achieved SVR12. Among 42 patients with HCV genotype 3b, all of whom had baseline resistance-associated substitutions in NS5A, 25 (89% [95% CI 72-98]) of 28 patients without cirrhosis and seven (50% [23-77]) of 14 patients with cirrhosis achieved SVR12. The most common adverse events were upper respiratory tract infection (36 [10%] patients) and headache (18 [5%] patients). There were no discontinuations due to adverse events. Serious adverse events were reported in three (1%) patients, none of which was judged to be related to sofosbuvir-velpatasvir treatment. INTERPRETATION: Consistent with data from other phase 3 studies, single-tablet sofosbuvir-velpatasvir for 12 weeks is an efficacious and safe treatment for Asian patients with chronic HCV infection, but might have lower efficacy in those infected with HCV genotype 3b and with cirrhosis. FUNDING: Gilead Sciences.


Assuntos
Antivirais/uso terapêutico , Carbamatos/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Cirrose Hepática/sangue , Sofosbuvir/uso terapêutico , Adulto , China , Combinação de Medicamentos , Feminino , Genótipo , Cefaleia/induzido quimicamente , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Infecções Respiratórias/induzido quimicamente , Singapura , Resposta Viral Sustentada , Tailândia , Resultado do Tratamento , Vietnã
8.
Gut ; 68(4): 721-728, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29666174

RESUMO

OBJECTIVE: We evaluated the efficacy and safety of ledipasvir/sofosbuvir alone and with ribavirin for 8 and 12 weeks in Egyptian patients with and without cirrhosis, who were infected with hepatitis C virus (HCV) genotype 4, including those who had failed previous treatment with sofosbuvir regimens. DESIGN: In this open-label, multicentre, phase III study, treatment-naive patients were randomised to receive 8 or 12 weeks of ledipasvir/sofosbuvir±ribavirin. Interferon treatment-experienced patients were randomised to receive 12 weeks of ledipasvir/sofosbuvir±ribavirin, while sofosbuvir-experienced or ledipasvir/sofosbuvir-experienced patients received 12 weeks of ledipasvir/sofosbuvir+ribavirin. Randomisation was stratified by cirrhosis status. The primary endpoint was sustained virological response 12 weeks post-treatment (SVR12). RESULTS: We enrolled 255 patients from four centres in Egypt. Among treatment-naive patients, SVR12 rates were 95% and 90% for those receiving 8 weeks of ledipasvir/sofosbuvir alone and with ribavirin, respectively, and 98% for those receiving 12 weeks of ledipasvir/sofosbuvir both alone and with ribavirin. Among interferon-experienced patients, SVR rates were 94% for those receiving 12 weeks of ledipasvir/sofosbuvir and 100% for those receiving 12 weeks of ledipasvir/sofosbuvir plus ribavirin. All patients previously treated with sofosbuvir regimens who received ledipasvir/sofosbuvir plus ribavirin achieved SVR12. The most common adverse events, headache and fatigue, were more common among patients receiving ribavirin. CONCLUSION: Among non-cirrhotic treatment-naive patients with HCV genotype 4, 8 weeks of ledipasvir/sofosbuvir±ribavirin was highly effective. Twelve weeks of ledipasvir/sofosbuvir±ribavirin was highly effective regardless of presence of cirrhosis or prior treatment experience, including previous treatment with sofosbuvir or ledipasvir/sofosbuvir. TRIAL REGISTRATION NUMBER: NCT02487030.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Uridina Monofosfato/análogos & derivados , Adulto , Idoso , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Egito , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C Crônica/genética , Humanos , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Ribavirina/uso terapêutico , Sofosbuvir , Resultado do Tratamento , Uridina Monofosfato/uso terapêutico
9.
Clin Drug Investig ; 38(3): 239-247, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29177645

RESUMO

BACKGROUND AND OBJECTIVES: The efficacy of < 12 weeks of hepatitis C virus (HCV) treatment in patients co-infected with HCV and human immunodeficiency virus type 1 (HIV-1) has not been established. We assessed the efficacy and safety of ledipasvir-sofosbuvir for 8 weeks in HCV mono-infected and HCV/HIV-1 co-infected patients. METHODS: We enrolled patients mono-infected with genotype 1 HCV or co-infected with HCV and HIV-1 who were HCV treatment-naive and did not have cirrhosis. HCV/HIV-1 co-infected patients were either not receiving antiretroviral treatment and had a CD4 T-cell count > 500 cells/mm3 or were receiving a protocol-approved antiretroviral regimen for ≥ 8 weeks (or ≥ 6 months for abacavir-containing regimens) and had HIV-1 RNA < 50 copies/mL and a CD4 T-cell count > 200 cells/mm3. Patients received ledipasvir-sofosbuvir (90/400 mg) once daily for 8 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after treatment discontinuation (SVR12). RESULTS: The SVR12 rate was 100% (67/67) for HCV mono-infected patients and 97% (57/59) for HCV/HIV-1 co-infected patients. Two patients relapsed by the week 4 post-treatment visit. Overall, the most common adverse events were headache (52%) and upper abdominal pain (26%). There were no serious adverse events or treatment discontinuations due to adverse events. No HCV/HIV-1 co-infected patients receiving antiretroviral treatment experienced HIV virologic rebound, and no clinically meaningful changes in CD4 T-cell counts were observed in any co-infected patient. CONCLUSIONS: Non-cirrhotic, treatment-naive patients with genotype 1 HCV mono-infection and HCV/HIV-1 co-infection achieved high rates of SVR12 with 8 weeks of treatment with ledipasvir/sofosbuvir. ClinicalTrials.gov identifier: NCT02472886.


Assuntos
Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Genótipo , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Uridina Monofosfato/análogos & derivados , Adulto , Idoso , Coinfecção , Comorbidade , Esquema de Medicação , Quimioterapia Combinada , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Hepacivirus/genética , Hepatite C/sangue , Hepatite C/epidemiologia , Humanos , Cirrose Hepática , Masculino , Pessoa de Meia-Idade , Sofosbuvir , Resposta Viral Sustentada , Resultado do Tratamento , Uridina Monofosfato/administração & dosagem , Carga Viral/efeitos dos fármacos
10.
Gastroenterology ; 151(5): 902-909, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27486033

RESUMO

BACKGROUND & AIMS: Studies are needed to determine the optimal regimen for patients with chronic hepatitis C virus (HCV) genotype 2, 3, 4, or 6 infections whose prior course of antiviral therapy has failed, and the feasibility of shortening treatment duration. We performed a phase 2 study to determine the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in these patients. METHODS: We performed a multicenter, open-label trial at 32 sites in the United States and 2 sites in New Zealand from March 3, 2015 to April 27, 2015. Our study included 128 treatment-naïve and treatment-experienced patients (1 with HCV genotype 1b; 33 with HCV genotype 2; 74 with HCV genotype 3; 17 with genotype HCV 4; and 3 with HCV genotype 6), with or without compensated cirrhosis. All patients received sofosbuvir-velpatasvir (400 mg/100 mg fixed-dose combination tablet) and GS-9857 (100 mg) once daily for 6-12 weeks. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). RESULTS: After 6 weeks of treatment, SVR12s were achieved by 88% of treatment-naïve patients without cirrhosis (29 of 33; 95% confidence interval, 72%-97%). After 8 weeks of treatment, SVR12s were achieved by 93% of treatment-naïve patients with cirrhosis (28 of 30; 95% CI, 78%-99%). After 12 weeks of treatment, SVR12s were achieved by all treatment-experienced patients without cirrhosis (36 of 36; 95% CI, 90%-100%) and 97% of treatment-experienced patients with cirrhosis (28 of 29; 95% CI, 82%-100%). The most common adverse events were headache, diarrhea, fatigue, and nausea. Three patients (1%) discontinued treatment due to adverse events. CONCLUSIONS: In a phase 2 open-label trial, we found sofosbuvir-velpatasvir plus GS-9857 (8 weeks in treatment-naïve patients or 12 weeks in treatment-experienced patients) to be safe and effective for patients with HCV genotype 2, 3, 4, or 6 infections, with or without compensated cirrhosis. ClinicalTrials.gov ID: NCT02378961.


Assuntos
Antivirais/uso terapêutico , Carbamatos/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Compostos Macrocíclicos/uso terapêutico , Sofosbuvir/uso terapêutico , Sulfonamidas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Serina Proteases , Resultado do Tratamento , Proteínas não Estruturais Virais , Adulto Jovem
11.
Gastroenterology ; 151(5): 893-901.e1, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27486034

RESUMO

BACKGROUND & AIMS: The best regimen to re-treat patients who do not respond to direct-acting antivirals (DAAs) and the feasibility of further shortening regimens is unclear. We assessed the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in patients with hepatitis C virus genotype 1 infection. METHODS: We performed an open-label trial at 32 sites in the United States and at 2 sites in New Zealand of 197 patients with genotype 1 hepatitis C virus infection, with or without compensated cirrhosis, who were treatment-naive or were treated previously with a DAA. Between March 2, 2015, and September 1, 2015, patients received sofosbuvir-velpatasvir (400 mg/100 mg in a fixed-dose combination) plus GS-9857 (100 mg) once daily for 6-12 weeks, plus ribavirin for 1 treatment group consisting of treatment-naive patients with cirrhosis. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). RESULTS: Among treatment-naive patients without cirrhosis, 71% (24 of 34; 95% confidence interval [CI], 53-85) achieved SVR12 after 6 weeks of treatment and 100% (36 of 36; 95% CI, 90%-100%) achieved SVR12 after 8 weeks of treatment. Among treatment-naive patients with cirrhosis, 94% (31 of 33; 95% CI, 80-99) achieved SVR12 after 8 weeks of treatment and 81% (25 of 31; 95% CI, 63-93) achieved SVR12 after 8 weeks of treatment with ribavirin. Among DAA-experienced patients treated for 12 weeks, 100% without cirrhosis (31 of 31; 95% CI, 89-100) and 100% with cirrhosis (32 of 32; 95% CI, 89-100) achieved SVR12. The most common adverse events were headache, diarrhea, fatigue, and nausea. One patient (<1%) discontinued treatment because of adverse events. CONCLUSIONS: In a phase 2 open-label trial, we found 8 weeks of treatment with sofosbuvir-velpatasvir plus GS-9857 to be safe and effective in treatment-naive patients; 12 weeks was safe and effective in patients previously treated with DAAs. The combination was safe and effective in patients with or without compensated cirrhosis. Clinicaltrials.gov no: NCT02378935.


Assuntos
Antivirais/uso terapêutico , Carbamatos/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Compostos Macrocíclicos/uso terapêutico , Sofosbuvir/uso terapêutico , Sulfonamidas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Genótipo , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Ribavirina/uso terapêutico , Serina Proteases , Resultado do Tratamento , Proteínas não Estruturais Virais/antagonistas & inibidores , Adulto Jovem
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