RESUMO
BACKGROUND/AIMS: Gilbert's syndrome is a frequent genetic conjugation abnormality associated with adverse drug effects. Genetic UDP glucuronosyltransferase (UGT)1A gene variants can influence gene transcription, inducibility and glucuronidation activity. Protease inhibitors used in human immunodeficiency virus (HIV) infection and chronic viral hepatitis can inhibit UGTs. Indinavir (IDV) can lead to hyperbilirubinemia in Gilbert's syndrome (UGT1A1*28), which does not explain interindividual severity differences and may thus involve additional UGT1A variants. METHODS: One hundred and twenty-five HIV patients receiving IDV and 427 healthy blood donors were genotyped for the presence of UGT1A1*28, UGT1A3 -66T/C, UGT1A7 -57T/G, UGT1A7(N129K/R131K) using Taqman 5' nuclease assays. RESULTS: Hyperbilirubinemia was observed in 42%. UGT1A1*28 frequencies did not differ between HIV patients and controls but were significantly higher in hyperbilirubinemic patients. The frequency of homozygous carriers of the 4 UGT1A marker haplotype increased with hyperbilirubinemia affecting all patients with bilirubin levels >85 micromol/l. CONCLUSIONS: In IDV treatment the risk of severe hyperbilirubinemia is associated with genetic variants of the UGT1A3 and UGT1A7 genes in addition to Gilbert's syndrome (UGT1A1*28). This haplotype is a useful predictor of protease inhibitor-induced side effects.
Assuntos
Doença de Gilbert/tratamento farmacológico , Doença de Gilbert/genética , Glucuronosiltransferase/genética , Hiperbilirrubinemia/induzido quimicamente , Hiperbilirrubinemia/epidemiologia , Indinavir/efeitos adversos , Inibidores de Proteases/efeitos adversos , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Genótipo , Haplótipos/genética , Humanos , Indinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Inibidores de Proteases/uso terapêutico , Fatores de RiscoAssuntos
Vírus da Encefalite Transmitidos por Carrapatos/isolamento & purificação , Encefalite Transmitida por Carrapatos/diagnóstico , RNA Viral/isolamento & purificação , RNA Viral/urina , Urina/virologia , Idoso , Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , Sangue/virologia , Líquido Cefalorraquidiano/virologia , Vírus da Encefalite Transmitidos por Carrapatos/genética , Encefalite Transmitida por Carrapatos/virologia , Feminino , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Viral/sangue , RNA Viral/genética , Fatores de TempoRESUMO
OBJECTIVE: To describe the efficacy and change in lipid profile in patients with severe hyperlipidemia after switch to an atazanavir-containing highly active antiretroviral therapy regimen. DESIGN AND METHODS: Open-field, 24-week, prospective observational cohort study including 33 HIV-infected, antiretroviral-experienced patients with hyperlipidemia. Changes in lipid profiles were evaluated by analyses of triglycerides, total cholesterol, high- and low-density lipoprotein (HDL and LDL) cholesterol, and efficacy by HIV RNA and CD4 cell changes, both from baseline to week 24. RESULTS: A rapid and significant decrease of 46% (5.81 +/- 4 mmol/L vs. 3.16 +/- 2.6 mmol/L, P = 0.002) in triglyceride levels was shown. Similarly, a sustained improvement of 18% was observed in total cholesterol levels during the first 24 weeks after switching to atazanavir (6.45 +/- 1.9 mmol/L vs. 5.3 +/- 1.3 mmol/L, P = 0.001). After 24 weeks of treatment there was a significant decrease of 22% in non-HDL cholesterol (5.76 +/- 1.9 mmol/L at baseline vs. 4.5 +/- 1.3 mmol/L at 24 weeks; P = 0.003). HDL and LDL cholesterol profiles did not change significantly as did the viral load or CD4 cell count. CONCLUSIONS: Switching to atazanavir results in a significant improvement in HIV therapy-induced hyperlipidemia. A switch to atazanavir is proposed as a valuable option to improve atherogenic lipid profiles while maintaining virologic control.