This review addresses relevant aspects of Chagas disease in the immunocompromised host. Chagas disease--one of the world's most neglected diseases-has become a global public health concern. Novel transmission modalities, such as organ transplantation, evidence of parasite persistence in chronically infected individuals--with the potential for reactivation under immunosuppression--and the prolonged survival of immunosuppressed patients call for an appraisal of the disease in this particular setting. The management and outcome of solid organ transplantation in the infected recipient with special focus on heart transplantation is addressed. The guidelines for management and the outcome of the recipients of organs from infected donors are discussed, and comments on haematopoietic stem cell transplantation are included. Finally, Chagas disease in other situations of impairment of the immune system, such as HIV/AIDS and autoimmune diseases, are considered. Immunosuppression has become an increasingly frequent condition that might modify the natural history of Trypanosoma cruzi infection. A number of strategies are available for Chagas disease management in the immunosuppressed patient. First, according to recent recommendations from the health authorities in Argentina, most infected patients would benefit from being treated at diagnosis. This has not been validated for patients with different immunosuppressive disorders. A different strategy would involve treating only patients with documented reactivation (either parasitaemia or clinical manifestations). These different approaches are discussed. To reach a diagnosis of parasitaemia, monitoring is essential, either with conventional methods or with molecular techniques that are not yet available in all centres. Collaborative studies are needed to improve the level of evidence, which will allow for better guidelines.

ObjectiveAcquired immune deficiency appears to be associated with serious non-AIDS (SNA)-defining conditions such as cardiovascular disease, liver and renal insufficiency and non-AIDS-related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort. Materials and methodsCases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV-associated factors on non-AIDS-defining conditions. ResultsAmong 6007 patients in follow-up, 130 had an SNA event (0.86 events/100 person-years of followup) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non-AIDS-defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T-cell count prior to index date (P 5 0.0056, with an average difference of more than 100 cells/mL) and area under the CD4 cell curve in the year previous to index date (P 5 0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors. ConclusionsThe incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.

IntroductionThe use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals.Materials and MethodsA set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed.ResultsNone of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count.DiscussionNo associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

resultados. La mediana de edad fue de 81 años, 61% mujeres. Los factores desencadenantes más frecuentes fueron la tos persistente y la inyección de heparina de bajo peso molecular. El 70% estaban anticoagulados, de ellos el 57% presentaba INR en rango supraterapéutico y en el 45% se suspendió la anticoagulación de manera definitiva tras el ingreso. El 41% presentaban insuficiencia renal crónica y la creatinina en el momento del diagnóstico fue superior a la basal (p<0,001). El tratamiento fue conservador en la mayoría de casos; se realizó radiología intervencionista en tres pacientes (6,5%) y cirugía abierta en cuatro (8,7%). El tratamiento invasivo se aplicó a pacientes con hematomas de mayor tamaño y con mayores requerimientos transfusionales, y se asoció a una mayor estancia media (p<0,001).conclusiones. El HEMR es más frecuente en pacientes ancianos, tratados con acenocumarol y en rango supraterapéutico y conlleva con frecuencia la suspensión definitiva del tratamiento anticoagulante. La insuficiencia renal aparece relacionada con la sobredosificación del tratamiento anticoagulante y con la producción del hematoma. El tamaño del HEMR y los requerimientos transfusionales son factores que parecen relacionados con mayor necesidad de tratamiento invasivo mediante embolización arterial o cirugía. results. The median age of patients was 81 years, 61% were female. The most frequent triggers were persistent coughing and injection of low molecular weight heparin. Seventy percent were anticoagulated, of which 57% had INR in the supratherapeutic range, and in 45% anticoagulation was definitively discontinued after admission. Forty-one percent presented chronic renal failure; moreover, creatinine at the time of diagnosis was higher than baseline (p <0.001). In most cases, treatment was conservative; interventional radiology was performed on three patients (6.5%) and open surgery on four (8.7%). Invasive treatment was employed with patients who had larger hematomas and higher transfusion requirements, and this was associated with a longer mean stay (p<0.001).conclusions. RSH is more frequent in elderly patients, treated with acenocumarol and in the supratherapeutic range, and frequently entails permanent suspension of anticoagulant therapy. Renal insufficiency is related to the overdosage of the anticoagulant treatment and to the production of the hematoma. The size of RSH and transfusion requirements are factors that seem to be related to a greater need for invasive treatment through arterial embolization or surgery.