Search

BackgroundInflammasome activation is increased in people with human immunodeficiency virus (PWH), but its relationship with coronary plaque is poorly understood in this setting.MethodsIn a large human immunodeficiency virus cardiovascular prevention cohort, relationships between caspase-1, interleukin (IL)-1β, and IL-18 and coronary plaque indices were assessed by multivariate logistic regression.ResultsHigher IL-18 and IL-1β were associated with Leaman score, an integrative measure of plaque burden and composition.ConclusionsAs Leaman score >5 is associated with cardiovascular events in the general population, future work is needed to determine how the inflammasome relates to events and whether strategies to reduce its activation affect events or plaque progression among PWH.

People with HIV have a higher risk of fracture than the general population. Because of the low performance of the existing prediction tools, there is controversy surrounding fracture risk estimation in this population. The aim of the study was to develop a model for predicting the long‐term risk of fragility fractures in people with HIV. We included 11,899 individuals aged ≥30 years from the Spanish HIV/AIDS research network cohort. We identified incident fragility fractures from medical records, defined as nontraumatic or those occurring after a casual fall, at major osteoporotic sites (hip, clinical spine, forearm, proximal humerus). Our model accounted for the competing risk of death and included 12 candidate predictors to estimate the time to first fragility fracture. We assessed the discrimination and calibration of the model and compared it with the FRAX tool. The incidence rate of fragility fractures was 4.34 (95% CI 3.61 to 5.22) per 1000 person‐years. The final prediction model included age, chronic kidney disease, and chronic obstructive pulmonary disease as significant predictors. The model accurately predicted the 5‐ and 10‐year risk of fragility fractures, with an area under the receiving operator characteristic curve of 0.768 (95% CI 0.722 to 0.814) and agreement between the observed and expected probabilities. Furthermore, it demonstrated better discrimination and calibration than the FRAX tool, improving the classification of over 35% of individuals with fragility fractures compared to FRAX. Our prediction model demonstrated accuracy in predicting the long‐term risk of fragility fractures. It can assist in making personalized intervention decisions for individuals with HIV and could potentially replace the current tools recommended for fracture risk assessment in this population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Current guidelines recommend screening people with HIV (PWH) for bone disease using predictive tools developed for the general population, although data on PWH are scarce. In this study, we assessed the performance of FRAX and QFracture scoring systems to predict the occurrence of fragility fractures in a prospective cohort of 17,671 adults with human immunodeficiency virus (HIV) included in the HIV/AIDS research network (CoRIS) in Spain. The survival estimates of fragility fractures during follow-up were calculated and FRAX and QFracture scores were computed at cohort inclusion. For both tools, discriminatory measures and the observed-to-expected (O/E) ratios were assessed. During a follow-up time of 42,411.55 person-years, 113 fragility fractures were recorded. Areas under the curve were 0.66 [95% confidence interval (95% CI) 0.61–0.71] for FRAX and 0.67 (95% CI 0.62–0.73) for QFracture for major osteoporotic fractures, and 0.72 (95% CI 0.57–0.88) and 0.81 (95% CI 0.68–0.95) for hip fracture, respectively. The O/E was 1.67 for FRAX and 5.49 for QFracture for major osteoporotic fractures, and 11.23 for FRAX and 4.87 for QFracture for hip fractures. Moreover, O/E raised as the risk increased for both tools and in almost all age groups. When using the recommended assessment thresholds, <6% and 10% of major osteoporotic and hip fractures would have been identified, respectively. In conclusion, FRAX and QFracture displayed acceptable discrimination, although both tools significantly underestimated the risk of fragility fractures in PWH. The recommended assessment thresholds may not be appropriate for this population as they were unable to identify individuals with fragility fractures during follow-up. [ABSTRACT FROM AUTHOR]

Despite in vitro activity of interferon-β (IFN-β) against SARS-CoV-2 infection, its clinical efficacy remains controversial. We evaluated the impact of IFN-β treatment in a cohort of 3590 patients hospitalized with COVID-19 during March–April 2020. The primary endpoint was a composed variable of admission to intensive care unit (ICU)/death. Overall, 153 patients (4%) received IFN-β. They were significantly more severely ill, with a worse clinical and analytical situation, explaining a higher ICU admission (30% vs. 17%; p < 0.01), and a shorter time to the composed variable. In a Cox regression analysis, older age, lymphopenia, renal failure, or increased neutrophil-to-lymphocyte ratio were associated with a greater hazard ratio (HR) of admission at ICU/death. Notably, the HR of IFN-β for the outcome variable was no longer significant after adjustment (HR, 1.03; 95% CI, 0.82–1.30), and different sensitivity analysis (early IFN use, ICU admission) showed no changes in the estimates. A propensity score matching analysis showed no association of IFN-β therapy and outcome. In conclusion, in this large cohort of hospitalized COVID-19 patients, IFN-β was used mainly in patients with advanced disease, reflecting an important bias of selection. After adjusting by severity, IFN-β was not associated with a higher rate of ICU admission or mortality. [ABSTRACT FROM AUTHOR]

People living with HIV-1 and HTLV-2 concomitantly show slower CD4+ T cell depletion and AIDS progression, more frequency of the natural control of HIV-1, and lower mortality rates. A similar beneficial effect of this infection has been reported on HCV coinfection reducing transaminases, increasing the spontaneous clearance of HCV infection and delaying the development of hepatic fibrosis. Given the critical role of CD8+ T cells in controlling HIV-1 infection, we analysed the role of CD8+ T cell-mediated cytotoxic activity in coinfected individuals living with HIV-1. One hundred and twenty-eight individuals living with HIV-1 in four groups were studied: two groups with HTLV-2 infection, including individuals with HCV infection (N = 41) and with a sustained virological response (SVR) after HCV treatment (N = 25); and two groups without HTLV-2 infection, including individuals with HCV infection (N = 25) and with a sustained virological response after treatment (N = 37). We found that CD8+ T cell-mediated HIV-1 inhibition in vitro was higher in individuals with HTLV-2. This inhibition activity was associated with a higher frequency of effector memory CD8+ T cells, higher levels of granzyme A and granzyme B cytolytic enzymes, and perforin. Hence, cellular and soluble cytolytic factors may contribute to the lower HIV-1 pre-ART viral load and the HIV-1 proviral load during ART therapy associated with HTLV-2 infection. Herein, we confirmed and expanded previous findings on the role of HTLV-2 in the beneficial effect on the pathogenesis of HIV-1 in coinfected individuals. [ABSTRACT FROM AUTHOR]