RESUMEN
OBJECTIVES: The response rate to treatment of chronic hepatitis C virus-genotype 1 and 4 infections was recently found to be strongly influenced by many polymorphisms. The aim of our study was to carry out an integrated analysis of the effects of polymorphisms and ribavirin (RBV) plasma exposure on outcome. METHODS: The retrospective analysis included 174 patients. IL28B, CYP27B1, SLC29A1, SLC28A3, and SLC28A2 polymorphisms were genotyped and tested for association with sustained virological response. The impact of RBV plasma exposure during the first 3 months of therapy on outcome was also investigated. RESULTS: Considering patients infected by hepatitis C virus-1/4, 3 polymorphisms (IL28B rs8099917TT, CYP27B1 rs4646536TT, and CNT2 rs11854484TT) were associated with sustained virological response. The number of negative variant allele and low RBV exposure were correlated to percentage increasing to therapy failure, suggesting some degree of cumulative effect of the 4 factors. A cutoff of 2.5 µg/mL of RBV was found to be associated with outcome (area under ROC [AUROC] curve = 0.64, sensitivity = 55.0%, and specificity = 71.2%, P = 0.020). In multivariate logistic regression analyses, each variant allele and RBV plasma exposure cutoff were independently associated with outcome. CONCLUSIONS: In this study, we found that additional polymorphisms and RBV plasma exposure are also able to influence the achievement of response. Regardless of the magnitude of RBV pharmacokinetic exposure, the negative predictive value of the polymorphisms here investigated is much stronger than the positive one.
Asunto(s)
25-Hidroxivitamina D3 1-alfa-Hidroxilasa/genética , Antivirales/farmacocinética , Hepatitis C/tratamiento farmacológico , Interleucinas/genética , Proteínas de Transporte de Membrana/genética , Polimorfismo de Nucleótido Simple , Ribavirina/farmacocinética , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/metabolismo , Adulto , Antivirales/sangre , Antivirales/uso terapéutico , Interacciones Farmacológicas , Monitoreo de Drogas , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Estudios de Asociación Genética , Hepacivirus/efectos de los fármacos , Hepatitis C/sangre , Hepatitis C/metabolismo , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Interferones , Interleucinas/metabolismo , Italia , Masculino , Proteínas de Transporte de Membrana/metabolismo , Persona de Mediana Edad , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Ribavirina/sangre , Ribavirina/uso terapéuticoRESUMEN
The effect of HAART on HCV infection and HCV-RNA plasma levels is controversial. We describe a patient with HIV-HCV coinfection with persistent disappearance of HCV-RNA after immunological and virological response to HAART, and we briefly discuss similar cases reported in the literature.
Asunto(s)
Terapia Antirretroviral Altamente Activa , Infecciones por VIH/complicaciones , Hepatitis C/complicaciones , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Hepacivirus/genética , Hepatitis C/sangre , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Inducción de RemisiónRESUMEN
Worldwide, tuberculosis (TB) is one of the most important infectious diseases in subjects with HIV infection. Although effective therapy is available for both conditions, there are major problems in the concurrent treatment of HIV and TB co-infection. In this article the knowledge available on drug-drug interactions between anti-HIV and anti-TB compounds is analysed, particularly with regard to pharmacological interactions secondary to interference with cytochrome P450 enzymes. Within the same setting, facts and possible interpretations of the problems encountered in terms of tolerance and safety of the concurrent treatment of TB and HIV are also reviewed. Current guidelines, as well as additional possible strategies to be adopted in this particular co-morbidity setting are discussed.
