GASPAR LISBOA NETO
Projetos de Pesquisa
Unidades Organizacionais
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
3 resultados
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- Prevalence of naturally occurring amino acid substitutions associated with resistance to hepatitis C virus NS3/NS4A protease inhibitors in Sao Paulo state(2018) MOREIRA, Regina Celia; SANTOS, Ana Paula de Torres; LISBOA-NETO, Gaspar; MENDES-CORREA, Maria Cassia Jacintho; LEMOS, Marcilio Figueiredo; MALTA, Fernanda Mello; SANTANA, RAbia Anita Ferraz; DASTOLI, Gregorio Tadeu Fernando; CASTRO, Vanessa Fusco Duarte de; PINHO, Joao Renato RebelloHepatitis C (HCV)-infected patients are treated with direct-acting antiviral agents (DAAs) in highly effective, well-tolerated, all-oral regimens. However, naturally occurring resistance-associated amino acid substitutions (RASs) may be selected during treatment. This study aimed to screen naturally occurring RASs NS3/NS4A inhibitors (PIs). Samples were obtained from DAA naive patients, living in Sao Paulo state, Brazil. Screening for RASs in the HCV NS3 region was conducted in 859 samples from HCV-infected patients, of which 425 and 434 samples were subtype la and lb, respectively. HCV-RNA was extracted, amplified, and sequenced. The overall prevalence of RASs to HCV PIs was 9.4%. The following RASs were observed in HCV-1a subtype infected patients: V36L (2.6%), T54S (1.6%), V55I/A (1.2% / 8.9%, respectively), Q80K (2.1%), R155K (0.5%), and D168E (0.2%); and in HCV-1b infected patients: V36L (0.7%), T54A/S (0.2% and 0.5%, respectively), V55A (0.5%), Q80K (0.2%), D168E (1.6%), and M175L (0.5%). HCV la infected subjects had higher serum viral load than that seen in patients infected with HCV 1b. There was no difference between the proportions of NS3 RASs with regards to geographic distribution within the investigated areas. These findings should be supported by additional studies in Brazil to help in the formation of local clinical guidelines for managing hepatitis C.
- Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil(2017) MALTA, Fernanda; GASPARETO, Karine Vieira; LISBOA-NETO, Gaspar; CARRILHO, Flair Jose; MENDES-CORREA, Maria Cassia; PINHO, Joao Renato RebelloBackground: Non-structural 5A protein (NS5A) resistance-associated substitutions (RASs) have been identified in patients infected with hepatitis C virus (HCV), even prior to exposure to direct-acting antiviral agents (DAAs). Selection for these variants occurs rapidly during treatment and, in some cases, leads to antiviral treatment failure. DAAs are currently the standard of care for hepatitis C treatment in many parts of the world. Nevertheless, in Brazil, the prevalence of pre-existing NS5A RASs is largely unknown. In this study, we evaluated the frequency of naturally occurring NS5A RASs in Brazilian patients infected with HCV as either a monoinfection or coinfection with human immunodeficiency virus (HIV). Methods: Direct Sanger sequencing of the NS5A region was performed in 257 DAA-naive patients chronically infected with HCV (156 monoinfected with HCV and 101 coinfected with HIV/HCV). Results: The frequencies of specific RASs in monoinfected patients were 14.6% for HCV GT-1a (M28 V and Q30H/R), 6.0% for GT-1b (L31F/V and Y93H), and 22.6% for GT-3a (A30K and Y93H). For HIV/HCV-coinfected patients, the frequencies of RAS were 3.9% for GT-1a (M28 T and Q30H/R), and 11.1% for GT-1b (Y93H); no RASs were found in GT-3a sequences. Conclusions: Substitutions that may confer resistance to NS5A inhibitors exist at baseline in Brazilian DAA-naive patients infected with HCV GT-1a, -1b, and -3a. Standardization of RAS definitions is needed to improve resistance analyses and to facilitate comparisons of substitutions reported across studies worldwide. Therapeutic strategies should be optimized to efficiently prevent DAA treatment failure due to selection for RASs, especially in difficult-to-cure patients.
- Natural occurrence of NS5B inhibitor resistance-associated variants in Brazilian patients infected with HCV or HCV and HIV(2017) NOBLE, Caroline Furtado; MALTA, Fernanda; LISBOA-NETO, Gaspar; GOMES-GOUVEA, Michele Soares; LEITE, Andrea Gurgel Batista; CASTRO, Vanessa Fusco Duarte de; SANTANA, Rubia Anita Ferraz; CARRILHO, Flair Jose; MENDES-CORREA, Maria Cassia; PINHO, Joao Renato RebelloResistance-associated variants (RAVs) represent a challenge to the success of new HCV therapies. The aim of this study was to describe the prevalence of naturally occurring NS5B RAVs in Brazilian direct acting antivirals (DAA)-na < ve patients infected with HCV genotype 1, or co-infected with HIV. Patient enrollment and sample collection were performed between 2011 and 2013. Using Sanger-based sequencing, 244 sequences were obtained. RAVs detected in HCV-1a sequences were V321A (1.6 %), M414V (1.3 %), A421V (21.4-23.7 %), A421G (1.3 %) and Y448H (1.3 %); and in HCV-1b sequences were L159F (16.1 %), C316N (7.1-16.3 %) and A421V (3.2-6.3 %). Understanding the real RAVs scenario in patients is fundamental to establishing the most effective therapeutic strategy and in minimizing the risks for their selection.