RESUMEN
The continual improvement in outcome with highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) infection and visceral transplantation for gut failure stimulated our interest in lifting HIV infection as a contraindication for intestinal and multivisceral transplantation. This report is the first to describe visceral transplantation in a patient with HIV infection. A HAART regimen was introduced in the setting of short-gut syndrome with successful suppression of HIV viral load. The indication for en bloc multivisceral and kidney transplantation was end-stage liver failure with portomesenteric venous thrombosis and chronic renal insufficiency. The underlying hepatic pathology was alcoholic and home parenteral nutrition-associated cirrhosis. Surgery was complicated due to technical difficulties with excessive blood loss and long operative time. The complex posttransplant course included multiple exploratory laparotomies due to serious intra-abdominal and systemic infections. Heavy immunosuppression was required to treat recurrent episodes of severe allograft rejection. Posttransplant oral HAART successfully sustained undetectable viral load. Unfortunately, the patient succumbed to sepsis 3 months posttransplant. With new insights into the biology of gut immunity, mechanisms of allograft tolerance, and HIV-associated immune dysregulation, successful outcome is anticipated, particularly in patients who are in need of isolated intestinal and less-organ-contained visceral allografts.
Asunto(s)
Rechazo de Injerto/diagnóstico , Infecciones por VIH/complicaciones , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Fallo Hepático/cirugía , Complicaciones Posoperatorias , Vísceras/trasplante , Adulto , Femenino , Rechazo de Injerto/etiología , Supervivencia de Injerto , VIH/patogenicidad , Infecciones por VIH/virología , Humanos , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/etiología , Fallo Hepático/etiología , Masculino , Persona de Mediana Edad , Trasplante de Órganos , Pronóstico , Adulto JovenRESUMEN
We report the case of a male heart transplant recipient who developed acute antibody-mediated rejection and was treated with 5 weeks of a rituximab-containing regimen. Two months later he presented with progressive motor and cognitive impairments and was diagnosed with progressive multifocal leukoencephalopathy (PML). He was treated with reduction of his immunosuppressive medications, mirtazapine, IVIG and plasmapheresis. He died within weeks. We reviewed the current literature on PML and its association with immunosuppression, highlighting its impact in the setting of solid organ transplantation and considering the potential effect of newer biologic drugs on the incidence of this devastating disease in the transplant population.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Rechazo de Injerto/terapia , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/terapia , Trasplante de Corazón , Leucoencefalopatía Multifocal Progresiva/complicaciones , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Trastornos del Conocimiento/complicaciones , Resultado Fatal , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunosupresores/efectos adversos , Masculino , Mianserina/análogos & derivados , Mianserina/uso terapéutico , Persona de Mediana Edad , Mirtazapina , Plasmaféresis , RituximabRESUMEN
We evaluated the replication efficiency of the HIV reverse transcriptase (RT) mutants K103N, G190A, and G190S, which confer resistance to the non-nucleoside RT inhibitor efavirenz, using growth competition assays in cell culture. In the absence of efavirenz, the fitness hierarchy was G190S < G190A < K103N < wild-type. The fitness reduction of G190S relative to K103N was less evident at high efavirenz concentrations, although K103N still replicated more efficiently. Efficiency of RNase H cleavage and RNA-dependent DNA synthesis from tRNA(Lys, 3) correlated with relative fitness, in biochemical studies of mutant RTs. Presteady state and steady state polymerization assays using DNA primers detected no abnormalities. This work is consistent with previous studies demonstrating that initiation of viral DNA synthesis is reduced in mutants with slowed RNase H cleavage, and suggests that both abnormalities contribute to the replication defect of these mutants. It also suggests that high concentrations of efavirenz are unlikely to favor the selection of G190S clinically.