HIV status, burden of comorbid disease, and biomarkers of inflammation, altered coagulation, and monocyte activation

Abstract

Background: Biomarkers of inflammation, altered coagulation, and monocyte activation are associated with mortality and cardiovascular disease (CVD) in the general population and among human immunodeficiency virus (HIV)-infected people. We compared biomarkers for inflammation, altered coagulation, and monocyte activation between HIV-infected and uninfected people in the Veterans Aging Cohort Study (VACS).

Methods: Biomarkers of inflammation (interleukin-6 [IL-6]), altered coagulation (d-dimer), and monocyte activation (soluble CD14 [sCD14]) were measured in blood samples from 1525 HIV-infected 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-infected 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-infected veterans with HIV-1 RNA ≥500 copies/mL or CD4 count <200 cells/µL had a significantly higher prevalence of elevated IL-6 (odds ratio [OR], 1.54; 95% confidence interval [CI],1.14-2.09; OR, 2.25; 95% CI, 1.60-3.16, respectively) and d-dimer (OR, 1.97; 95% CI, 1.44-2.71, OR, 1.68; 95% CI, 1.22-2.32, respectively) after adjusting for comorbidities. HIV-infected veterans with a CD4 cell count <200 cells/µL 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.

Conclusions: These data suggest that ongoing HIV replication and immune depletion significantly contribute to increased prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation. This contribution is independent of and in addition to the substantial contribution from comorbid conditions.

Figure 1.

Distribution of age- and race/ethnicity-adjusted interleukin 6 (IL-6), d-dimer, and soluble CD14 (sCD14) levels by human immunodeficiency virus (HIV) status, HIV-1 RNA level, and CD4 lymphocyte count.