Resistance mutations are rare among protease inhibitor treatment-naive hepatitis C genotype-1 patients with or without HIV coinfection

Autor(es):Mostrar menos -

Lisboa-Neto, Gaspar ^[1] ; Noble, Caroline F. ^[2] ; Rebello Pinho, Joao R. ^{[2, 3]} ; Malta, Fernanda M. ^[2] ; Gomes-Gouvea, Michele S. ^[2] ; Alvarado-Mora, Monica V. ^[2] ; da Silva, Mariliza H. ^{[4, 5]} ; Leite, Andrea G. B. ^[6] ; Piccoli, Leonora Z. ^[6] ; Rodrigues, Flaviane K. ^[7] ; Carrilho, Flair J. ^[2] ; Mendes-Correa, Maria C. ^{[1, 7]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Dept Infect Dis, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Sch Med, Lab Trop Gastroenterol & Hepatol Joao Alves de Qu, LIM 07, Inst Trop Med, Dept Gastroenterol, Sao Paulo, SP - Brazil

^[3] Hosp Israelita Albert Einstein, Albert Einstein Med Diagnost, Sao Paulo, SP - Brazil

^[4] Ctr Referencia & Treinamento DST AIDS Estado Sao, Sao Paulo, SP - Brazil

^[5] Clin Especialidades, Sao Bernardo Do Campo, SP - Brazil

^[6] Ctr Especializado Saude, Caxias Do Sul, RS - Brazil

^[7] ABC Fdn Med Sch, Infect Dis Res Unit, Santo Andre, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ANTIVIRAL THERAPY; v. 20, n. 3, p. 281-287, 2015.
• Citações Web of Science: 11

Resumo

Background: HCV has a high replication rate and a lack of proofreading activity, leading to a greatly diverse viral population. This diversity may lead to emergence of resistant strains in direct-acting antiviral therapy. The frequency of naturally occurring HCV protease inhibitor (PI) mutations has been addressed in many countries, but there are few data on the prevalence of these mutations in Brazilian patients. Methods: We evaluated the sequence of HCV NS3 protease gene in 247 patients (135 HCV-monoinfected and 112 HIV-HCV-coinfected patients). HCV RNA was extracted from plasma and a fragment of 765 base pairs from the NS3 region was amplified and sequenced with Sanger-based technology. Results: HIV-HCV-coinfected patients were more likely to be older than 40 years and have an HCV subtype-1a infection. Overall, 21.9% of patients had at least one amino acid substitution in the NS3 region; 14 patients (5.7%) harboured at least one resistance mutation (T54S, V55A, Q80R) and the Q80K mutation was not found in our case series. There was no difference between monoinfected and coinfected patients regarding the frequency of natural polymorphisms and resistance mutations. Conclusions: Baseline HCV NS3 amino acid substitutions identified herein are considered mostly natural polymorphisms with no clinical impact on PI-based therapy. The identified resistance mutations may be associated with low-level resistance to PIs in vitro. Q80K substitution seems to be a rare event in Brazil. HIV coinfection was not associated with a greater frequency of such substitutions in the studied sample. (AU)

• Processo FAPESP: 08/50461-6 - Estudo da variabilidade genotípica dos vírus da Hepatite B e Hepatite C na Colômbia
• Beneficiário: Monica Viviana Alvarado Mora
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 09/53306-4 - Perfil de celulas nk e dendriticas em casos de soroconversao espontanea e infeccao cronica pelo virus da hepatite.
• Beneficiário: Fernanda de Mello Malta
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/50081-9 - Prevalência de resistência primária aos antivirais utilizados no tratamento da hepatite B entre pacientes com infecção crônica pelo vírus da hepatite B não submetidos a tratamento
• Beneficiário: Michele Soares Gomes Gouvêa
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 11/50633-4 - Identificação das mutações de resistência antiviral para inibidores de protease (NS3/4A) e polimerase (NS5B) para o vírus da hepatite C presentes em pacientes co-infectados HCV-HIV: estudo de uma série de casos
• Beneficiário: Maria Cássia Jacintho Mendes Corrêa
• Modalidade de apoio: Auxílio à Pesquisa - Regular