RESUMO
BACKGROUND: Interactions between antiretrovirals (ARVs) and transplant immunosuppressant agents (IS) among HIV-infected transplant recipients may lead to lack of efficacy or toxicity. In transplant recipients not infected with HIV, tacrolimus (TAC) trough levels (C0) or cyclosporine (CsA) drawn at C0 or 2 hours after dosing (C2) correlate with drug exposure (area under the curve [AUC]/dose) and outcomes. Because of ARV-IS interactions in HIV-infected individuals, and the high rate of rejection in these subjects, this study investigated the correlations between IS concentrations and exposure to determine the best method to monitor immunosuppressant levels. METHODS: This study prospectively studied 50 HIV-infected transplant recipients undergoing kidney or liver transplantation evaluating the pharmacokinetics of the IS in 150 studies over time after transplantation (weeks 2 to 4, 12, 28, 52, and 104). IS levels were measured with liquid chromatography-tandem mass spectrometry and AUC calculated using WinNonlin 9.0. Correlation analyses were run on SAS 9.2. RESULTS: CsA concentration at C4 correlated better with AUC than C0 or C2, and over time TAC concentration correlated better at C0 or C2. CONCLUSIONS: It is suggested that C0 is acceptable for TAC monitoring, but poor predictability will occur at C0 with CsA. The low correlation of C0 with CsA AUC could be responsible for the higher rejection rates on CsA that has been reported in these subjects.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Ciclosporina/farmacocinética , Monitoramento de Medicamentos , Infecções por HIV/tratamento farmacológico , Imunossupressores/farmacocinética , Transplante de Rim , Transplante de Fígado , Tacrolimo/farmacocinética , Adolescente , Adulto , Idoso , Área Sob a Curva , Cromatografia Líquida , Ciclosporina/administração & dosagem , Ciclosporina/sangue , Interações Medicamentosas , Monitoramento de Medicamentos/métodos , Feminino , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/sangue , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Tacrolimo/administração & dosagem , Tacrolimo/sangue , Espectrometria de Massas em Tandem , Resultado do Tratamento , Adulto JovemRESUMO
HIV infection has evolved into a chronic condition as a result of improvements in therapeutic options. Chronic exposure with HIV and associated co-pathogens as well as toxicities from prolonged therapy with antiviral medications has resulted in increased morbidity and mortality rates from end-stage liver and kidney disease in the HIV-infected population. Since the definitive treatment for end-stage organ failure is transplantation, demand has increased among HIV-infected patients. Although the transplant community has been slow to recognize HIV as a chronic condition, many transplant centers have eliminated HIV infection as a contraindication to transplantation as a result of better patient management and demand. This review examines the current clinical strategies and issues surrounding liver and kidney transplantation in HIV-infected patients.
