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  • Protocolo de Prevenção e Tratamento de Infeções Associadas à Terapêutica Imunossupressora de Doenças Autoimunes
    Publication . Valdoleiros, Sofia R.; Furtado, Isabel; Silva, Carolina; Correia Gonçalves, Inês; Santos Silva, André; Vasconcelos, Olga; Horta, Ana; Vasconcelos, A. Ludgero; Xará, Sandra; Gonçalves, Maria João; Abreu, Miguel; Sarmento-Castro, Rui
    We propose a guideline about the risk, prevention and treatment of infection in the patient under immunomodulatory or immunosuppressive therapy in the context of autoimmune or autoinflammatory disease. It is divided into three sections: drugs and associated risk of infection; immunizations; risk, prevention, and treatment of specific infections. The treatment of autoimmune diseases involves the use of immunosuppressive or immunomodulatory therapies, with an increasing number of new drugs being used. It is associated with an increased risk of infection, which may be present globally or only for specific agents, varying widely depending on the pharmacological class and even within the same class. The prevention strategy and clinical management need to be individually tailored and there are several key factors: characterization of the disease that prompts the immunosuppression, understanding of the mechanism of action of the immunosuppressive drug, knowledge of previous infections, recognition of risk factors, laboratory test results, vaccine administration, monitoring of clinical signs and symptoms and patient education.
  • Thymic Function as a Predictor of Immune Recovery in Chronically HIV-Infected Patients Initiating Antiretroviral Therapy
    Publication . Rb-Silva, R.; Nobrega, C.; Azevedo, C.; Athayde, E.; Canto-Gomes, J.; Ferreira, I.; Cheynier, R.; Yates, A.; Horta, Ana; Correia-Neves, M.
    Poor immunological responders (PIR) are HIV-infected patients with virologic suppression upon antiretroviral therapy (ART) but persistently low CD4+ T cell counts. Early identification of PIR is important given their higher morbimortality compared to adequate immune responders (AIR). In this study, 33 patients severely lymphopenic at ART onset, were followed for at least 36 months, and classified as PIR or AIR using cluster analysis grounded on their CD4+ T cell count trajectories. Based on a variety of immunological parameters, we built predictive models of PIR/AIR outcome using logistic regression. All PIR had CD4+ T cell counts consistently below 500 cells/μL, while all AIR reached this threshold. AIR showed a higher percentage of recent thymic emigrants among CD4+ T cells; higher numbers of sj-TRECs and greater sj/β TREC ratios; and significant increases in thymic volume from baseline to 12 months of ART. We identified mathematical models that correctly predicted PIR/AIR outcome after 36 months of therapy in 77-87% of the cases, based on observations made until 2-6 months after ART onset. This study highlights the importance of thymic activity in the immune recovery of severely lymphopenic patients, and may help to select the patients that will benefit from closer follow-up or novel therapeutic approaches.