Bengtsongunter3160

Background In well treated human immunodeficiency virus infection (HIV), there is a residual immune activation and immune exhaustion that may contribute to increased risk of comorbidities. T-cell immunoglobulin mucin domain-3 (Tim-3) is an inhibitory molecule involved in HIV-associated T-cell dysfunction. The Tim-3 can be cleaved to soluble Tim-3 (sTim-3) that may serve as a soluble marker of immune exhaustion. Methods We measured sTim-3 with enzyme-linked immunosorbent assay DuoSets in a cross-sectional cohort of 1010 people with HIV (PWH) on antiretroviral therapy (ART), and 76 controls from the Copenhagen Co-Morbidity in HIV Infection (COCOMO) study, and in a longitudinal cohort of 60 PWH before and during ART. Results In the cross-sectional cohort, levels of sTim-3 were elevated in PWH on ART compared with controls, especially in hepatitis C virus (HCV)-coinfected individuals, and were associated with HCV viremia and inflammation. In the longitudinal cohort, pretreatment sTim-3 correlated with HIV viral load and decreased after ART initiation. Pretreatment sTim-3 correlated inversely with CD4 counts, but it did not predict immunological response in multivariable analyses. Conclusions Levels of sTim-3 decreased after ART initiation. In a cross-sectional cohort, levels of sTIM-3 were higher in PWH than in controls and were independently associated with HCV coinfection and high-sensitivity C-reactive protein, representing a potential link between immune exhaustion, inflammation, and risk of comorbidities. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Background Multiple blood cultures have been shown to improve pathogen yield and antimicrobial stewardship for adult patients with suspected serious bacterial infection (SBI). For children, the use of multiple blood cultures is less common and volume recommendations are more complicated, often resulting in single cultures with low volume. Methods In 2010, Children's Hospital Colorado instituted electronic medical record (EMR) decision support to recommend collection of 2 blood cultures before administration of antibiotics for suspected SBI. Recommended blood culture volumes were calculated by age rather than weight. We evaluated all children admitted to inpatient units between 2008 and 2009 (pre-intervention) and 2011 and 2013 (postintervention) who received antibiotics in the hospital after having blood cultures drawn in the emergency department, excluding those with a length of stay >8 days. We compared blood culture yield, isolate classification (pathogen vs contaminant), and antimicrobial modifications before and after the interventions. Results A total of 3948 children were included in the study. KP-457 datasheet EMR guidelines were associated with a significantly higher number of children with multiple blood cultures drawn before antibiotic administration (88.0% vs 12.3%; P  less then  .001) and an increased percentage of blood cultures with the recommended volume (74.3% vs 15.2%; P  less then  .001), resulting in a significantly higher pathogen isolation rate and improved antimicrobial decisions. Multiple cultures helped define the role of common contaminants in the clinical decision process. Conclusions Multiple blood cultures with age-based volumes taken before starting antibiotics increase pathogen isolation rates and appropriate modification of antimicrobial treatment in children. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Background Coagulation activity among persons with HIV is associated with end-organ disease risk, but the pathogenesis is not well characterized. We tested a hypothesis that hypercoagulation contributes to disease risk, in part, via upregulation of inflammation. Methods Treatment effects of edoxaban (30 mg), a direct factor Xa inhibitor, vs placebo were investigated in a randomized, double-blind crossover trial among participants with HIV and viral suppression and D-dimer levels ≥100 ng/mL. During each 4-month crossover period, blood measures of coagulation, inflammation, and immune activation were assessed. Analyses of change on edoxaban vs change on placebo used linear mixed models. Results Forty-four participants were randomized, and 40 completed at least 1 visit during each study period. The mean age was 49 years, and the CD4+ count was 739 cells/mm3. Edoxaban treatment led to declines in D-dimer (44%) and thrombin-antithrombin complex (26%) but did not lower inflammatory or immune activation measures. More bruising or bleeding events occurred during edoxaban (n = 28) than during placebo or no drug periods (n = 15). Conclusions The direct factor Xa inhibitor edoxaban led to a substantial reduction in coagulation but no effect on inflammation or immune activation. These results do not support that hypercoagulation contributes to ongoing inflammation during chronic antiretroviral therapy-treated HIV disease. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.We report a case of fulminant Acanthamoeba castellanii encephalitis in a patient with chronic lymphocytic leukemia treated with ibrutinib. The unusually rapid neurologic decline and fatal outcome observed are probably related to alterations in immunologic function associated with inhibition of Bruton tyrosine kinase. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Background The HIV epidemic is unevenly distributed throughout the United States, even within neighborhoods. This study evaluated how effectively current testing approaches reached persons at risk for HIV infection across San Diego (SD) County, California. Methods HIV case and testing data, sexually transmitted infection (STI) data, and sociodemographic data for SD County were collected from the SD Health and Human Services Agency and the "Early Test" community-based HIV screening program between 1998 and 2016. Relationships between HIV diagnoses, HIV prevalence, and STI diagnoses with screening at the ZIP code level were evaluated. Results Overall, 379 074 HIV tests were performed. The numbers of HIV tests performed on persons residing in a ZIP code or region overall strongly correlated with prevalent HIV cases (R 2 = .714), new HIV diagnoses (R 2 = .798), and STI diagnoses (R 2 = .768 [chlamydia], .836 [gonorrhea], .655 [syphilis]) in those regions. ZIP codes with the highest HIV prevalence had the highest number of tests per resident and fewest number of tests per diagnosis.