Revisão sistemática da eficácia e da segurança das terapias livres de interferon para hepatite C crônica em pacientes coinfectados com o Vírus da Imunodeficiência Humana

Ferreira, Vinicius Lins; Pedrozo, Regiellen Cristina; Góis, Fernando Rodrigues; Pontarolo, Roberto

doi:10.1590/0103-1104201711518

Vinicius Lins Ferreira

Universidade Federal do Paraná (UFPR), Programa de Pós-Graduação em Ciências Farmacêuticas - Curitiba (PR), Brasil. vinicius_lins1991@hotmail.com

Regiellen Cristina Pedrozo

Universidade Estadual do Centro-Oeste (Unicentro), Departamento de Farmácia - Guarapuava (PR), Brasil. regiellen@hotmail.com

Fernando Rodrigues Góis

Universidade Federal do Paraná (UFPR), Programa de Pós-Graduação em Ciências Farmacêuticas - Curitiba (PR), Brasil. gois@ebiotecnologia.org

Roberto Pontarolo

Universidade Federal do Paraná (UFPR), Programa de Pós-Graduação em Ciências Farmacêuticas - Curitiba (PR), Brasil. pontarolo@ufpr.br

Conflito de interesses: inexistente

Colaboradores

Vinicius Lins Ferreira: projetou o estudo, extraiu e analisou os dados, realizou a avaliação da qualidade metodológica, escreveu o artigo e aprovou a primeira versão do manuscrito.

Regiellen Cristina Pedrozo: projetou o estudo, extraiu e analisou os dados, realizou a avaliação da qualidade metodológica, escreveu o artigo e aprovou a primeira versão do manuscrito.

Fernando Rodrigues Góis: revisou a primeira versão do manuscrito e aprovou a versão final do artigo.

Roberto Pontarolo: supervisionou a execução do projeto, revisou e aprovou a versão final do artigo.

Autor	Nome do estudo	Jadad	Terapia	Tempo de tratamento	Local de estudo	N	Gênero Masculino (%)	Idade (anos)	VHC Genótipo	Cirróticos (%)	ET (%)
(BASU; SHAH; BROWN JR., 2015BASU, P. P.; SHAH, N. J.; BROWN, J. R. R. Simeprevir and sofosbuvir with modified doses of ribavirin (RBV) therapy on telaprevir experienced co infected (with HIV) cirrhotics with chronic hepatitis C (CHC). A randomized open label clinical pilot study: Stop C. Journal of Hepatology, Copehnagen, v. 62, p. S643, 2015. Disponível em: <http://www.journal-of-hepatology.eu/article/S0168-8278(15)31022-9/abstract>. Acesso em: 2 maio 2016. http://www.journal-of-hepatology.eu/arti... )	Stop C	1	SOF+SMV+RBV	24 e 16	NR	50	NR	NR	1 (100%)	100	NR
(*LUETKEMEYER ET AL., 2016*LUETKEMEYER, A. F. et al. 12 Weeks of Daclatasvir in Combination with Sofosbuvir for HIV-HCV Coinfection (ALLY-2 Study): Efficacy and Safety by HIV Combination Antiretroviral Regimens. Clinical Infectious Diseases, Chicago, v. 62, n. 12, p. 1489-1496, 2016. Disponível em: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885650/>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pmc/article... )	ALLY-2	2	DCV+SOF	16	EUA	151	88,7	53	1 (84%), 2 (8%), 3 (6%) e 4 (2%)	15,2	34
(*MOLINA ET AL.,* 2015**MOLINA, J. M. et al. Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study. The Lancet, Londres, v. 385, n. 9973, p. 1098-106, fev. 2015. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/25659285>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2565... )	PHOTON-2	1	SOF+RBV	24 ou 12	>2 países	274	80,6	49,6	1 (40%), 2 (9%), 3 (38%) e 4 (11%)	19,7	20
(*NAGGIE ET AL., 2015*NAGGIE, S. et al. Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1. New England Journal Of Medicine, Massachusetts, v. 373, n. 8, p. 705-13, 2015.)	ION-4	1	LED+SOF	12	EUA e Porto Rico	335	82	52	1 (98%) e 4 (2%)	20	55
(*OSINUSI ET AL., 2015*OSINUSI, A. et al. Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection. Journal of the American Medical Association, Chigado, v. 313, n. 12, p. 1232-1239, 2015. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/25706232>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2570... )	NR	1	LED+SOF	12	EUA	50	74	58,2	1 (100%)	0	0
(*ROCKSTROH ET AL., 2015*ROCKSTROH, J. K. et al. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. The Lancet HIV, Amsterdam, v. 2, n. 8, p. 319-327, 2015. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/26423374>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2642... )	C-EDGE CO-INFECTION	1	GRA+ELB	12	>2 países	218	84	48,7	1 (86%), 4 (13%) e 6 (1%)	16	0
(*SULKOWSKI ET AL., 2014*SULKOWSKI, M. S. et al. Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection. Journal of the American Medical Association, Chicago, v. 312, n. 4, p. 353-361, 2014. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/25706092>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2570... )	NR	1	SOF+RBV	12 ou 24	EUA e Porto Rico	223	83	50,3	1 (51%), 2 (30%) e 3 (20%)	10	18,3
(*SULKOWSKI, M. ET AL., 2015A*SULKOWSKI, M. S. et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. The Lancet, Londres, v. 385, n. 9973, p. 1087-1097, 2015a. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/25467560>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2546... )	C-WORTHY	3	GRA+ELB±RBV	12	>2 países	59	79,6	46,2	1 (100%)	0	0
(*SULKOWSKI, M. S. ET AL., 2015B*SULKOWSKI, M. S. et al. Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. Journal of the American Medical Association, Chicago, v. 313, n. 12, p. 1223-1231, 2015b. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/25706092>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2570... )	Turquoise-I	3	PrOD+RBV	12 ou 24	EUA e Porto Rico	63	92	50,9	1 (100%)	19	33
(*WYLES ET AL., 2015*WYLES, D. L. et al. Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1. New England Journal Of Medicine, Massachusetts, v. 373, n. 8, p. 714-25, 2015.)	ALLY-2	2	DCV+SOF	8 ou 12	EUA	203	87,1	53,3	1 (83%), 2 (9%), 3 (6%) e 4 (1%)	14	26

Autor	Nome do estudo	Tratamento	Tempo de tratamento	N	RVR (%)	TDT (%)	SVR4 (%)	SVR12 (%)	FVDT (%)	FVAT (%)
(BASU; SHAH; BROWN JR., 2015BASU, P. P.; SHAH, N. J.; BROWN, J. R. R. Simeprevir and sofosbuvir with modified doses of ribavirin (RBV) therapy on telaprevir experienced co infected (with HIV) cirrhotics with chronic hepatitis C (CHC). A randomized open label clinical pilot study: Stop C. Journal of Hepatology, Copehnagen, v. 62, p. S643, 2015. Disponível em: <http://www.journal-of-hepatology.eu/article/S0168-8278(15)31022-9/abstract>. Acesso em: 2 maio 2016. http://www.journal-of-hepatology.eu/arti... )	Stop C	SOF+SMV+RBV	24 e 16	50	70	82	NR	82	NR	NR
(*LUETKEMEYER ET AL., 2016*LUETKEMEYER, A. F. et al. 12 Weeks of Daclatasvir in Combination with Sofosbuvir for HIV-HCV Coinfection (ALLY-2 Study): Efficacy and Safety by HIV Combination Antiretroviral Regimens. Clinical Infectious Diseases, Chicago, v. 62, n. 12, p. 1489-1496, 2016. Disponível em: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885650/>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pmc/article... )	ALLY-2	DCV+SOF	16	151	NR	NR	NR	97	NR	2,6
(*MOLINA ET AL.,* 2015**MOLINA, J. M. et al. Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study. The Lancet, Londres, v. 385, n. 9973, p. 1098-106, fev. 2015. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/25659285>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2565... )	PHOTON-2	SOF+RBV	24 ou 12	274	97	95	88,6	86,4	0,3	12
(*NAGGIE ET AL., 2015*NAGGIE, S. et al. Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1. New England Journal Of Medicine, Massachusetts, v. 373, n. 8, p. 705-13, 2015.)	ION-4	LED+SOF	12	335	99	NR	97	96	1	3
(*OSINUSI ET AL., 2015*OSINUSI, A. et al. Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection. Journal of the American Medical Association, Chigado, v. 313, n. 12, p. 1232-1239, 2015. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/25706232>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2570... )	NR	LED+SOF	12	50	100	100	98	98	NR	2
(*ROCKSTROH ET AL., 2015*ROCKSTROH, J. K. et al. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. The Lancet HIV, Amsterdam, v. 2, n. 8, p. 319-327, 2015. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/26423374>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2642... )	C-EDGE CO-INFECTION	GRA+ELB	12	218	NR	NR	NR	96,3	0	5
(*SULKOWSKI ET AL., 2014*SULKOWSKI, M. S. et al. Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection. Journal of the American Medical Association, Chicago, v. 312, n. 4, p. 353-361, 2014. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/25706092>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2570... )	NR	SOF+RBV	12 ou 24	223	97	91	82,5	79	0,8	17
(*SULKOWSKI, M. ET AL., 2015A*SULKOWSKI, M. S. et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. The Lancet, Londres, v. 385, n. 9973, p. 1087-1097, 2015a. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/25467560>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2546... )	C-WORTHY	GRA+ELB±RBV	12	59	NR	NR	NR	91	3	1,6
(*SULKOWSKI, M. S. ET AL., 2015B*SULKOWSKI, M. S. et al. Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. Journal of the American Medical Association, Chicago, v. 313, n. 12, p. 1223-1231, 2015b. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/25706092>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2570... )	Turquoise-I	PrOD+RBV	12 ou 24	63	100	NR	94	92	1,5	1,5
(*WYLES ET AL., 2015*WYLES, D. L. et al. Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1. New England Journal Of Medicine, Massachusetts, v. 373, n. 8, p. 714-25, 2015.)	ALLY-2	DCV+SOF	8 ou 12	EUA	NR	NR	NR	92	0	6

Autor	Nome do estudo	Tratamento	Tempo de tratamento	N	Qualquer EA (%)	EA sério (%)	Descontinuação por EA (%)	Diarreia (%)	Fadiga (%)	Dor de cabeça (%)	Náusea (%)
(BASU; SHAH; BROWN JR., 2015BASU, P. P.; SHAH, N. J.; BROWN, J. R. R. Simeprevir and sofosbuvir with modified doses of ribavirin (RBV) therapy on telaprevir experienced co infected (with HIV) cirrhotics with chronic hepatitis C (CHC). A randomized open label clinical pilot study: Stop C. Journal of Hepatology, Copehnagen, v. 62, p. S643, 2015. Disponível em: <http://www.journal-of-hepatology.eu/article/S0168-8278(15)31022-9/abstract>. Acesso em: 2 maio 2016. http://www.journal-of-hepatology.eu/arti... )	Stop C	SOF+SMV+RBV	24 e 16	50	NR	NR	NR	NR	NR	NR	NR
(*LUETKEMEYER ET AL., 2016*LUETKEMEYER, A. F. et al. 12 Weeks of Daclatasvir in Combination with Sofosbuvir for HIV-HCV Coinfection (ALLY-2 Study): Efficacy and Safety by HIV Combination Antiretroviral Regimens. Clinical Infectious Diseases, Chicago, v. 62, n. 12, p. 1489-1496, 2016. Disponível em: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885650/>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pmc/article... )	ALLY-2	DCV+SOF	16	151	72,8	2,6	0	9,3	18,5	13,2	13,9
(*MOLINA ET AL.,* 2015**MOLINA, J. M. et al. Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study. The Lancet, Londres, v. 385, n. 9973, p. 1098-106, fev. 2015. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/25659285>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2565... )	PHOTON-2	SOF+RBV	24 ou 12	274	90	5	2	11	20,4	15,6	14,2
(*NAGGIE ET AL., 2015*NAGGIE, S. et al. Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1. New England Journal Of Medicine, Massachusetts, v. 373, n. 8, p. 705-13, 2015.)	ION-4	LED+SOF	12	335	77	2	0	11	21	25	10
(*OSINUSI ET AL., 2015*OSINUSI, A. et al. Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection. Journal of the American Medical Association, Chigado, v. 313, n. 12, p. 1232-1239, 2015. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/25706232>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2570... )	NR	LED+SOF	12	50	100	2	0	8	10	10	6
(*ROCKSTROH ET AL., 2015*ROCKSTROH, J. K. et al. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. The Lancet HIV, Amsterdam, v. 2, n. 8, p. 319-327, 2015. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/26423374>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2642... )	C-EDGE CO-INFECTION	GRA+ELB	12	218	74	1	0	7	13	12	9
(*SULKOWSKI ET AL., 2014*SULKOWSKI, M. S. et al. Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection. Journal of the American Medical Association, Chicago, v. 312, n. 4, p. 353-361, 2014. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/25706092>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2570... )	NR	SOF+RBV	12 ou 24	223	NR	6,2	3	10	37,6	13,4	16,1
(*SULKOWSKI, M. ET AL., 2015A*SULKOWSKI, M. S. et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. The Lancet, Londres, v. 385, n. 9973, p. 1087-1097, 2015a. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/25467560>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2546... )	C-WORTHY	GRA+ELB± RBV	12	59	57,6	3,3	0	1,7	6	8,4	1,6
(*SULKOWSKI, M. S. ET AL., 2015B*SULKOWSKI, M. S. et al. Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. Journal of the American Medical Association, Chicago, v. 313, n. 12, p. 1223-1231, 2015b. Disponível em: <https://www.ncbi.nlm.nih.gov/pubmed/25706092>. Acesso em: 20 maio 2016. https://www.ncbi.nlm.nih.gov/pubmed/2570... )	Turquoise-I	PrOD+RBV	12 ou 24	63	88,8	0	0	8	47,6	15,8	17,4
(*WYLES ET AL., 2015*WYLES, D. L. et al. Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1. New England Journal Of Medicine, Massachusetts, v. 373, n. 8, p. 714-25, 2015.)	ALLY-2	DCV+SOF	8 ou 12	EUA	69	2	0	7,3	16,7	11,3	12,8

[1] Conflito de interesses: inexistente

Brasil

Brasil

Revisão sistemática da eficácia e da segurança das terapias livres de interferon para hepatite C crônica em pacientes coinfectados com o Vírus da Imunodeficiência Humana

Systematic review of the efficacy and safety of interferon-free therapies for chronic hepatitis C in patients coinfected with the Human Immunodeficiency Virus

RESUMO