RESUMO
BACKGROUND: In HIV infected patients, the impact of ribavirin (RBV) pharmacology on sustained virologic response (SVR) to hepatitis C virus (HCV) treatment has not been fully investigated. The objective of this study was to compare the early RBV plasma exposure between a population of HIV-HCV coinfected patients and an HCV monoinfected group. METHODS: Early RBV plasma exposure (expressed as Area Under the Curve (AUC) from 0 to 4 h) after a 600 mg first dose of RBV was measured in a population of HIV-HCV coinfected patients in comparison with an HCV monoinfected group. Peripheral blood samples were collected before the 600 mg RBV first dose (T0) to ensure no detectable baseline plasma RBV, and then 30 mn, 1, 2 and 4 hours after RBV intake (T0.5, T1, T2 and T4). RESULTS: Eighty-six patients with chronic hepatitis C entered the study among whom 23 (27%) were HIV-HCV coinfected. Coinfected patients had a significantly lower RBV-AUC(0-4h) (median: 1469 µg*h/L [range 936-3677]) compared with monoinfected patients (2030 µg*h/L [851-7700]; p = 0.018). This RBV under exposure in coinfected patients persisted after normalization of AUC to RBV dose per kilogram of body weight (182 µg*h/L [110-425] versus 271 µg*h/L [82-1091], p = 0.001). CONCLUSIONS: These results suggest that lower early bioavailability of RBV could be one of the reasons for lower SVR in HIV-HCV coinfected patients treated with pegylated interferon/RBV combination therapy. RBV plasma underexposure seems to be associated with the immunological status of the patients with lower AUC(0-4h) values observed in the more immunosuppressed coinfected patients.
Assuntos
Antivirais/farmacocinética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Hepatite C Crônica/metabolismo , Ribavirina/farmacocinética , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/sangue , Disponibilidade Biológica , Coinfecção , Feminino , Infecções por HIV/sangue , Infecções por HIV/virologia , Hepatite C Crônica/sangue , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Ribavirina/administração & dosagem , Ribavirina/sangue , Adulto JovemRESUMO
BACKGROUND: Anemia is more frequent in patients receiving telaprevir with PEGylated interferon/ribavirin (PEG-IFN/RBV) than in those receiving PEG-IFN/RBV alone. OBJECTIVES: The objective was to measure the impact of telaprevir on RBV bioavailability and to assess the concomitant renal function. MATERIALS AND METHODS: Thirty-seven hepatitis C virus (HCV) patients non-responders to a previous course of PEG-IFN/RBV therapy and re-treated with triple therapy combining PEG-IFN/RBV and telaprevir were analyzed. RBV bioavailability was measured before the triple therapy initiation, during telaprevir treatment at week (W) 4 and W8, and after telaprevir cessation (post W16). The renal function was assessed by estimating the glomerular filtration rate (eGFR). RESULTS: At W4, RBV bioavailability, expressed as mg/L/daily dose/kg body weight, was significantly increased (median increase = 0.06 mg/L/dose/kg; P < 0.001). In parallel, the renal function was impaired with a mean eGFR decrease of -6.8 mL/minutes/1.73 m² (P = 0.109). Between W4 and W8, RBV bioavailability continued to increase (P < 0.001) but subsequently decreased slightly after telaprevir discontinuation with a concomitant restoration of the renal function (eGFR increase of 6.34 mL/minutes/1.73 m²). CONCLUSIONS: Our results indicated a reversible increase in RBV bioavailability after telaprevir exposure, which might be linked to the impairment of the GFR. This also suggests a RBV-telaprevir pharmacological interaction, a possible source of severe anemia observed under triple therapy. These results suggest that RBV pharmacological monitoring may be clinically relevant, especially in the context of first-generation HCV protease inhibitor-based therapy.
RESUMO
Blood services are required to provide the safest possible products, but no transfusion can ever be totally free of the risk of transfusion transmissible infections (TTI). Over the past decade, the risk of TTI through transfusion has been reduced (e.g. 1 in 300 000 for HBV to 1 in 2 million for HIV). With the introduction in 1999 of sensitive and expensive nucleic acid testing (NAT) technology in some countries, the disease transmission rate and the window period have been significantly reduced, but a remaining concern is the chance that a blood donor will be infected and not detected by such tests. To obtain safe blood and blood components it is important to ensure that the donors are healthy and free from TTI by using a donor selection procedure meticulously made, using a donor questionnaire to assess donor health and safety and for reducing the risk of transmission of infection, in particular for infections for which no suitable screening tests are available. In Romania the prevalence of TTI among donor population is high in comparison with other European Union (EU) countries. This may require significant improvements in the screening process of both donors and donations to minimize the infectious risk.
Assuntos
Bancos de Sangue/normas , Doadores de Sangue , Transfusão de Sangue/estatística & dados numéricos , Infecções por HIV/prevenção & controle , Hepatite B/prevenção & controle , Hepatite C/prevenção & controle , Doadores de Sangue/legislação & jurisprudência , Doadores de Sangue/estatística & dados numéricos , União Europeia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Hepatite B/transmissão , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Hepatite C/transmissão , Humanos , Programas de Rastreamento/legislação & jurisprudência , Técnicas de Amplificação de Ácido Nucleico/métodos , Prevalência , Medição de Risco , Fatores de Risco , Romênia/epidemiologia , Inquéritos e QuestionáriosRESUMO
The infection with hepatitis C virus (HCV) known also as a blood-borne infection can be life-threatening by delayed consequences of persistent infection. This study aimed to estimate the hepatitis C infection prevalence, its epidemiological mode of manifestation and its recent evolution among blood donors from North West region of Romania. We made a chronological study using the HCV seropositive confirmed results to serological blood donors screening, provided by two Blood Transfusion Centres, chosen for their quality of provided data: Cluj and Satu Mare. The statistics were descriptive and the time series modelling used the polynomial regression. In both counties, about three fourth of donors were male and in Satu Mare, female donors (29.2%; p < 0.001) have been significantly more represented than in Cluj (24.6%). Hepatitis C virus seroprevalence was significantly (p < 0.01) higher in Satu Mare (279.8/10(5) donors, CI: 241.7-317.9/10(5) donors) than in Cluj (212.6/10(5) donors, CI: 187.4-237.8/10(5) donors). The mode of manifestation was endemic in different patterns, one with wave and a stable one with a particular high value of 1.091.1/10(5) female donors (CI: 674-1508.2/10(5) donors) seroprevalence, in 2008, in Satu Mare. The variation of the prevalence value was higher for women and particularly (coefficient of variation: 91.9%) for those from Satu Mare. The hepatitis C virus seroprevalence among blood donors reflected a stable, endemic manifestation with particular variation and high transmission in female populational subgroups.