GASPAR LISBOA NETO

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LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina

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Assunto: Infectious Diseases ×

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  • article 16 Citação(ões) na Scopus
    Resistance mutations are rare among protease inhibitor treatment-naive hepatitis C genotype-1 patients with or without HIV coinfection
    (2015) LISBOA-NETO, Gaspar; NOBLE, Caroline F.; PINHO, Joao R. Rebello; MALTA, Fernanda M.; GOMES-GOUVEA, Michele S.; ALVARADO-MORA, Monica V.; SILVA, Mariliza H. da; LEITE, Andrea G. B.; PICCOLI, Leonora Z.; RODRIGUES, Flaviane K.; CARRILHO, Flair J.; MENDES-CORREA, Maria C.
    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.
  • article 18 Citação(ões) na Scopus
    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 Rebello
    Background: 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.