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HIV Status, Burden of Comorbid Disease and Biomarkers of Inflammation, Altered Coagulation and Microbial Translocation-VA Study: important study because it finds cd4 & viral load & comorbid conditions independently associated with inflammation
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Reported by Jules Levin CROI 2012 March 5-8 Seattle WA
Kaku Armah*1, A Justice2,3, R Tracy4, A Butt5,6, M Goetz7,8, S Deeks9,10, D Rimland11,12, C Rinaldo1,5, J Baker13, M Freiberg1,5, and the VACS Project Team
1Univ of Pittsburgh Grad Sch of Publ Hlth, PA, US; 2VA Connecticut Hlthcare System, West Haven, US; 3Yale Univ Sch of Med, New Haven, CT, US; 4Univ of Vermont, Burlington, US; 5Univ of Pittsburgh Sch of Med, PA, US; 6VA Pittsburgh Hlthcare System, PA, US; 7Univ of California, Los Angeles, David Geffen Sch of Med, US; 8VA Greater Los Angeles Hlthcare System, CA, US; 9Univ of California, San Francisco, US; 10San Francisco Gen Hosp, CA, US; 11Emory Univ Sch of Med, Atlanta, GA, US; 12Atlanta VAMC, GA, US; and 13Univ of Minnesota Med Sch, Minneapolis, US
Summary of Results
· Compared to uninfected Veterans, HIV+ Veterans with HIV RNA ≥500 copies/mL had a higher prevalence of elevated IL-6 and D-dimer.
· HIV+ Veterans with CD4 counts <200 copies/mm3 had a higher prevalence of elevated IL-6, D-dimer, and sCD14 vs. uninfected Veterans.
· Age ≥60 years, current smoking, low HDL, current hazardous or past drinking were associated with higher prevalence of elevated IL-6.
Age ≥70 years, African American race/ethnicity, prevalent CVD, uncontrolled hypertension, low HDL, and renal disease were significantly associated with D-dimer.
High/very high triglycerides, hepatitis C, and renal disease were significantly associated with sCD14.
·The increased prevalence of elevated biomarkers among HIV+ Veterans occurred despite the fact that the uninfected Veterans had similar or higher
prevalence of comorbid conditions that were also strongly and significantly associated with prevalence of elevated biomarkers.
Conclusions
- These data suggest that both ongoing HIV replication and immune depletion and comorbid conditions like cardiovascular and renal diseases, are
contributing to the prevalence of elevated biomarkers associated with inflammation, altered coagulation, and microbial translocation.
- Future studies, including randomized clinical trials, should focus simultaneously on viremia reduction, CD4 cell restoration and treatment of non-HIV related comorbidity as a strategy to reduce mortality and cardiovascular disease risk.
Strengths & Limitations
Strengths: Large, well documented cohort; presence of important subgroups (African Americans, and people with hepatitis C and/or substance use
disorders).
Limitations: Cross-sectional study design; Use of a single biomarker to describe complex inflammatory processes; Overwhelmingly male cohort.
Abstract
Background: Biomarkers of inflammation, altered coagulation (AC), and microbial translocation (MT) are associated with mortality and cardiovascular disease (CVD) in the general population and among human immunodeficiency virus infected people (HIV+). We compared biomarkers for inflammation, AC, and MT between HIV+ and uninfected people in the Veterans Aging Cohort Study (VACS).
Methods: Biomarkers of inflammation (interleukin-6 (IL-6)), AC (D-dimer), and MT (soluble CD4 (sCD14)) were measured in blood samples from 1525 HIV+ and 843 uninfected VACS participants. Logistic regression was used to determine the association between HIV infection and prevalence of elevated (>75th percentile) biomarkers adjusting for confounding comorbidities.
Results: HIV+ Veterans had less prevalent CVD, hypertension, diabetes, obesity, hazardous drinking and renal disease, but more dyslipidemia, hepatitis C, and current smoking than uninfected Veterans.
Compared to uninfected Veterans, HIV+ Veterans with HIV RNA ≥500 copies/ml or CD4 count <200 cells/mm3 had a significantly higher prevalence of elevated IL-6 (OR: 1.54; 95% CI=1.14-2.09, OR: 2.25; 95% CI: 1.60-3.16 respectively) and Ddimer (OR: 1.97; 95% CI: 1.44-2.71, OR: 1.68; 95% CI: 1.22-2.32 respectively) after adjusting for comorbidities. HIV+ Veterans with a CD4 cell count <200 copies/mm3 had significantly higher prevalence of elevated sCD14 compared to uninfected Veterans (OR: 2.60; 95% CI: 1.64-4.14). These associations still persisted after restricting the analysis to Veterans without known confounding comorbid conditions.
Conclusion: These data suggest that ongoing HIV replication and immune depletion significantly contribute to increased prevalence of elevated biomarkers of inflammation, altered coagulation, and microbial translocation. This contribution is independent of and in addition to the substantial contribution from comorbid conditions.
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