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1.
Artigo em Inglês | MEDLINE | ID: mdl-19211929

RESUMO

Highly-active antiretroviral therapy (HAART) has proven remarkably effective for prolonging the life of patients with human immunodeficiency virus (HIV). However, while most HAART agents are safe, many have the potential to cause liver toxicity. Physicians must therefore consider the possibility of drug-induced liver injury in the management of HIV-infected patients, especially those with certain risk factors such as coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV), female gender, alcohol abuse, older age, or obesity. Understanding how, when, and why drug-related liver damage occurs is key to managing these patients safely and effectively. Knowledge of HAART-related liver effects will help ensure that patients receive the most benefit with the least toxicity from any given drug regimen. As more information about the mechanisms of drug related liver injury is known, clinicians will be better able to tailor therapies to suit individual situations, resulting in greater patient safety and outcomes.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/complicações , Hepatite B/complicações , Hepatite C/complicações , Humanos , Hepatopatias/epidemiologia , Hepatopatias/prevenção & controle , Hepatopatias/virologia , Prevalência , Fatores de Risco
2.
J Antimicrob Chemother ; 63(3): 575-8, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19151039

RESUMO

OBJECTIVES: The aim of this study was to compare amprenavir pharmacokinetics in HIV/hepatitis C virus (HCV)-co-infected cirrhotic patients receiving non-boosted fosamprenavir 700 mg twice daily with HCV/HIV-co-infected non-cirrhotic subjects and HIV-mono-infected subjects receiving fosamprenavir/ritonavir 700/100 mg twice daily. Liver stiffness at baseline and alanine aminotransferase levels at baseline and during follow-up were measured in order to find a correlation between drug levels and liver fibrosis or hepatotoxicity. METHODS: Amprenavir plasma concentration was determined by HPLC. Liver stiffness was measured by transient elastometry. Liver function tests were determined every 1-3 months during follow-up. RESULTS: Nineteen HIV-infected patients were included. Eight had chronic HCV hepatitis (group NC), five had HCV-related liver cirrhosis (group C) and six were HIV-mono-infected (group M). In group C patients, amprenavir C(trough), AUC(0-12) and half-life were 86%/83%, 64%/55% and 58%/59% lower when compared with controls and co-infected subjects without cirrhosis, respectively; conversely, drug clearance in cirrhotics was 181%/124% higher. In 3/5 cirrhotic patients (60%) and in 2/14 non-cirrhotic patients (14%), C(trough) was below the minimum target concentration of 400 ng/mL; nonetheless, in all these patients, HIV viral load was undetectable. No correlation was found between amprenavir pharmacokinetics and liver stiffness or hepatotoxicity at follow-up. CONCLUSIONS: On the basis of these data, it seems reasonable to boost fosamprenavir with ritonavir even in cirrhotic patients; amprenavir pharmacokinetics could not be predicted by liver stiffness and seem not to predict hepatotoxicity at follow-up.


Assuntos
Fármacos Anti-HIV/farmacocinética , Carbamatos/farmacocinética , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite C/complicações , Cirrose Hepática , Organofosfatos/farmacocinética , Sulfonamidas/farmacocinética , Adulto , Alanina Transaminase/sangue , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Carbamatos/administração & dosagem , Carbamatos/uso terapêutico , Cromatografia Líquida de Alta Pressão , Técnicas de Imagem por Elasticidade , Feminino , Furanos , HIV/isolamento & purificação , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Organofosfatos/administração & dosagem , Organofosfatos/uso terapêutico , Plasma/química , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Carga Viral
3.
AIDS ; 22(7): 857-61, 2008 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-18427204

RESUMO

OBJECTIVES: To investigate the association between insulin resistance and rapid virologic response. DESIGN: All consecutive HIV/hepatitis C virus coinfected patients who started peg-interferon alpha-2a (180 microg/week) and ribavirin 1000-1200 mg/day were analysed. METHODS: Insulin resistance was defined according to the homeostasis model of assessment-insulin resistance calculated as fasting insulin (mIU/l) x fasting glucose (mmol/l)/22.5. Rapid virologic response was defined as testing negative for hepatitis C virus-RNA after 4 weeks of therapy. Fasting levels of insulin and glucose in plasma were measured in all patients on the first day of treatment. Hepatitis C virus-RNA was determined by quantitative PCR assay (version 3.0). Hepatitis C virus-RNA was measured by qualitative PCR assay (COBAS 2.0) after 4 weeks of treatment. RESULTS: Seventy-four HIV/hepatitis C virus coinfected patients were enrolled [mean age 41.7 years (SD 5.3), 61 men, 54.1% with advanced fibrosis (F3-4 according to METAVIR classification), 52.4% with infection by hepatitis C virus genotype 1 or 4]. Rapid virologic response was reached by 30 subjects. In the multivariate analysis the independent predictors of rapid virologic response were: genotype 1 or 4 [adjusted odds ratio 0.18 (0.06-0.55)], hepatitis C virus-RNA < 400.000 UI/ml [adjusted odds ratio 0.229 (0.09-0.92)] and homeostasis model of assessment-insulin resistance more than 3.00 [adjusted odds ratio 0.1 (0.05-0.6)]. CONCLUSION: The homeostasis model of assessment-insulin resistance score should be evaluated and possibly corrected before starting anti-hepatitis C virus therapy.


Assuntos
Antivirais/uso terapêutico , Infecções por HIV/virologia , HIV , Hepatite C Crônica/virologia , Resistência à Insulina , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Glicemia/análise , Esquema de Medicação , Jejum , Feminino , Genótipo , HIV/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/metabolismo , Homeostase , Humanos , Insulina/sangue , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Reação em Cadeia da Polimerase/métodos , RNA Viral/análise , Proteínas Recombinantes , Ribavirina/uso terapêutico , Resultado do Tratamento , Carga Viral
4.
AIDS Rev ; 9(1): 16-24, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17474310

RESUMO

Hepatitis C virus-related long-term complications are nowadays a leading cause of morbidity and mortality in HIV-infected persons. According to international guidelines, all HIV/HCV-coinfected patients should be evaluated and, if eligible, treated with pegylated interferon plus ribavirin. The management of anti-HCV treatment side effects, which may be even more serious in HIV patients, is very important to minimize treatment early discontinuations. The purpose of this review is to supply clinicians with an update, provided by the most recent and relevant literature, of underlying mechanisms, incidence, and advice about the management of pegylated interferon and ribavirin side effects in HCV/HIV-coinfected patients.


Assuntos
Infecções por HIV/tratamento farmacológico , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Infecções por HIV/complicações , Hepatite C/complicações , Hepatite C/virologia , Humanos , Interferons/efeitos adversos , Interferons/uso terapêutico , Ribavirina/efeitos adversos , Ribavirina/uso terapêutico
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