RESUMO
INTRODUCTION: The sofosbuvir (SOF) plus ledipasvir (LDV) fixed dose combination is the first direct action antiviral (DAA) single-treatment regimen (STR) to be commercialized. It is approved for the treatment of Hepatitis C virus (HCV) genotypes 1,3,4,5 and 6. Following approval in 2014, new pharmacokinetics and pharmacodynamics data were reported, which led to important clinical applications. Areas covered: This article reviews the pharmacokinetic and pharmacodynamic properties of the SOF/LDV fixed dose combination for the treatment of HCV. The topics covered include data regarding the drug´s absorption, distribution, metabolism and excretion and antiviral activity strategies such as the clinical dose selection and treatment duration. Expert opinion: The SOF/LDV fixed dose combination has good pharmacological properties that lead to a high sustained virological response after 12 or 24 weeks of treatment; there is minimal interference with other drugs or associated renal or hepatic impairment, such that dose adjustment is not necessary.
Assuntos
Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Hepatite C/tratamento farmacológico , Uridina Monofosfato/análogos & derivados , Animais , Antivirais/farmacocinética , Antivirais/farmacologia , Benzimidazóis/farmacocinética , Benzimidazóis/farmacologia , Relação Dose-Resposta a Droga , Fluorenos/farmacocinética , Fluorenos/farmacologia , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C/virologia , Humanos , Sofosbuvir , Fatores de Tempo , Resultado do Tratamento , Uridina Monofosfato/administração & dosagem , Uridina Monofosfato/farmacocinética , Uridina Monofosfato/farmacologiaRESUMO
OBJECTIVE: A prospective analysis of the distribution of NK subsets and natural cytotoxicity receptors (NKp30/NKp46) in HIV patients with long-term HAART use and sustained virological and immunological response. METHODS: The main inclusion criteria were: at least 3 years' receipt of HAART; current CD4+ count ≥ 500 cells/mm3; undetectable viral load for at least 24 months; no hepatotropic virus co-infection. Percentages of CD56dim, CD56bright NK cells and CD56neg CD16+ cells were obtained. Expression of the NCRs, NKp30 and NKp46 was analysed in CD56+ cells. Thirty-nine infected patients and sixteen healthy donors were included in the study. RESULTS: The percentages of total CD56+ and CD56dim NK cells were significantly lower in HIV-infected patients than in healthy donors (70.4 vs. 50.3 and 80.9 vs. 66.1 respectively). The percentage of total CD56+ NK cells expressing NCR receptors was lower in HIV patients than in healthy donors (NKp30: 25.20 vs. 58.63; NKp46: 24.8 vs. 50.59). This was also observed for CD56dim and CD56bright NK cells. Length of time with undetectable HIV viral load was identified as an independent factor associated with higher expression of NKp30 and NKp46. CONCLUSION: Despite the prolonged and effective use of HAART, HIV-infected patients do not fully reconstitute the distribution of NK cells. Length of time with an undetectable viral load was related to greater recovery of NKp30/NKp46 receptors.