Circulating Levels of Tissue Factor Microparticle Procoagulant Activity Are Reduced With Antiretroviral Therapy and Are Associated With Persistent Inflammation and Coagulation Activation Among HIV-Positive Patients

Activation of coagulation pathways may contribute to risk for non-AIDS related conditions among HIV positive patients. We measured tissue factor-dependent procoagulant activity on circulating microparticles (MP-TF) in the plasma of 163 HIV positive participants, both untreated and treated, with viral suppression. MP-TF activity was 39% lower among treated versus untreated participants (p<0.001), which persisted in adjusted models (−36%; p=0.03). Among treated participants, MP-TF activity correlated modestly with D-dimer (r=0.24; p=0.01), vWF (r=0.36; p<0.001), and IL-6 (r=0.20; p=0.04) levels. Future research should focus on mechanisms driving residual functional TF activity and whether these alterations have clinical consequences for non-AIDS defining complications

Markers of Inflammation, Coagulation, and Renal Function Are Elevated in Adults with HIV Infection

(See the article by Kalayjian et al, on pages 1796-1805, and the editorial commentary by Dubé and Sattler, on pages 1783-1785.) Background. Human immunodeficiency virus (HIV) replication and immune activation may increase inflammation and coagulation biomarkers. Limited data exist comparing such biomarkers in persons with and without HIV infection. Methods. For persons 45-76 years of age, levels of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, D-dimer, and cystatin C were compared in 494 HIV-infected individuals in the Strategies for Management of Anti-Retroviral Therapy (SMART) study and 5386 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) study. For persons 33-44 years of age, hsCRP and IL-6 levels were compared in 287 participants in the SMART study and 3231 participants in the Coronary Artery Development in Young Adults (CARDIA) study. Results. hsCRP and IL-6 levels were 55% (P<.001) and 62% (P<.001) higher among HIV-infected participants than among CARDIA study participants. Compared with levels noted in MESA study participants, hsCRP, IL-6, D-dimer, and cystatin C levels were 50%, 152%, 94%, and 27% higher, respectively (P<.001 , for each), among HIV-infected participants. HIV-infected participants receiving antiretroviral therapy who had HIV RNA levels ≤400 copies/mL had levels higher (by 21% to 60%) (P<.001) than those in the general population, for all biomarkers. Conclusions. hsCRP, IL-6, D-dimer, and cystatin C levels are elevated in persons with HIV infection and remain so even after HIV RNA levels are suppressed with antiretroviral therapy. Additional research is needed on the pathophysiology of HIV-induced activation of inflammatory and coagulation pathways, to guide potential intervention

Factors associated with D-dimer levels in HIV-infected individuals.

BACKGROUND: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood. METHODS: In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol. RESULTS: Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels. CONCLUSIONS: D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels

Human immunodeficiency virus, hepatitis C, and inflammatory biomarkers in individuals with alcohol problems: a cross-sectional study

BACKGROUND: Assessing whether hepatitis C (HCV) co-infection with human immunodeficiency virus (HIV) is associated with increased inflammation is complex. The liver, integral to inflammatory biomarker synthesis, is compromised by HCV and alcohol abuse. Using single liver-synthesized biomarkers (e.g. C-reactive protein) to represent inflammation may not be appropriate in HIV/HCV co-infection. We hypothesized that 1) detectable HIV/HCV RNA was independently associated with increased inflammation; 2) a composite inflammation measure describes inflammation differently from single inflammatory biomarkers. METHODS: We compared inflammation by HIV/HCV group in a cohort of 361 HIV infected participants from the HIV-Longitudinal Interrelationships of Viruses and Ethanol study. Inflammatory biomarkers >75th percentile were considered elevated. Associations between HIV/HCV group and elevated biomarkers were analyzed as a composite measure (inflammatory burden) or individually. We defined inflammatory burden as number of concurrently elevated biomarkers. Biomarkers included interleukin-6 (IL-6), C-reactive protein (CRP), cystatin C, serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10). Covariates: alcohol, liver fibrosis, comorbidities, CD4 count, antiretroviral therapy, substance use. RESULTS: Detectable HIV and HCV RNA (OR = 2.49; 95% CI = 1.05–5.89) and detectable HCV RNA alone (2.95; 1.08–8.01) were independently associated with increased odds of having a greater inflammatory burden compared to undetectable viremia. Elevated IL-10 (7.79; 1.90–31.97) and TNF-α (7.70; 1.42–41.83) were independently associated with detectable HIV and HCV RNA. Elevated IL-10 was also associated with detectable HCV RNA alone (5.51; 1.17, 25.84). CONCLUSIONS: Detectable HIV and HCV replication versus undetectable replication was associated with inflammatory burden and certain inflammatory biomarkers independently of alcohol consumption, liver fibrosis and other comorbidities

Factors Associated with D-Dimer Levels in HIV-Infected Individuals

Matti A Ristola on työryhmän jäsen.Peer reviewe

Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS): Final Report of the ASCENDS Ad Hoc Science Definition Team

Improved remote sensing observations of atmospheric carbon dioxide (CO2) are critically needed to quantify, monitor, and understand the Earth's carbon cycle and its evolution in a changing climate. The processes governing ocean and terrestrial carbon uptake remain poorly understood,especially in dynamic regions with large carbon stocks and strong vulnerability to climate change,for example, the tropical land biosphere, the northern hemisphere high latitudes, and the Southern Ocean. Because the passive spectrometers used by GOSAT (Greenhouse gases Observing SATellite) and OCO-2 (Orbiting Carbon Observatory-2) require sunlit and cloud-free conditions,current observations over these regions remain infrequent and are subject to biases. These short comings limit our ability to understand and predict the processes controlling the carbon cycle on regional to global scales.In contrast, active CO2 remote-sensing techniques allow accurate measurements to be taken day and night, over ocean and land surfaces, in the presence of thin or scattered clouds, and at all times of year. Because of these benefits, the National Research Council recommended the National Aeronautics and Space Administration (NASA) Active Sensing of CO2 Emissions over Nights,Days, and Seasons (ASCENDS) mission in the 2007 report Earth Science and Applications from Space: National Imperatives for the Next Decade and Beyond. The ability of ASCENDS to collect low-bias observations in these key regions is expected to address important gaps in our knowledge of the contemporary carbon cycle.The ASCENDS ad hoc Science Definition Team (SDT), comprised of carbon cycle modeling and active remote sensing instrument teams throughout the United States (US), worked to develop the mission's requirements and advance its readiness from 2008 through 2018. Numerous scientific investigations were carried out to identify the benefit and feasibility of active CO2 remote sensing measurements for improving our understanding of CO2 sources and sinks. This report summarizes their findings and recommendations based on mission modeling studies, analysis of ancillary meteorological data products, development and demonstration of candidate technologies, anddesign studies of the ASCENDS mission concept

Data Assimilation Enhancements to Air Force Weathers Land Information System

The United States Air Force (USAF) has a proud and storied tradition of enabling significant advancements in the area of characterizing and modeling land state information. 557th Weather Wing (557 WW; DoDs Executive Agent for Land Information) provides routine geospatial intelligence information to warfighters, planners, and decision makers at all echelons and services of the U.S. military, government and intelligence community. 557 WW and its predecessors have been home to the DoDs only operational regional and global land data analysis systems since January 1958. As a trusted partner since 2005, Air Force Weather (AFW) has relied on the Hydrological Sciences Laboratory at NASA/GSFC to lead the interagency scientific collaboration known as the Land Information System (LIS). LIS is an advanced software framework for high performance land surface modeling and data assimilation of geospatial intelligence (GEOINT) information