Abstract

WEPE094 - Poster Exhibition

Factors associated with elevated D-dimer levels in HIV-positive individuals

A. Borges¹, J. O'Connor², A. Phillips², J. Baker³, M. Vjecha⁴, M. Losso⁵, H. Klinker⁶, G. Lopardo⁷, I. Williams², J. Lundgren¹, for the INSIGHT SMART, ESPRIT and SILCAAT Study Groups

¹University of Copenhagen, Rigshospitalet, Copenhagen HIV Programme, Copenhagen, Denmark, ²University College London Medical School, London, United Kingdom, ³University of Minnesota, Department of Medicine, Minneapolis, United States, ⁴Veterans Affairs Medical Center, Washington, United States, ⁵Hospital JM Ramos Mejia, Buenos Aires, Argentina, ⁶University of Wuerzburg Medical Center, Würzburg, Germany, ⁷Fundación Centro de Estudios Infectológicos, Buenos Aires, Argentina

Background: In the SMART and ESPRIT studies, elevated D-dimer levels were strong predictors of all-cause mortality. The factors associated with elevated D-dimer levels during HIV infection, however, remain poorly understood.
Methods: In this cross-sectional study, all SMART, ESPRIT and SILCAAT participants with available D-dimer measurements at baseline were included (N= 9,837). Factors independently associated with elevated D-dimer levels were identified by linear and logistic regression models. The following predictors were investigated: age, gender, race, body mass index, markers of inflammation (CRP and IL-6), past and current exposure to different ART classes. For linear regression, log₁₀-transformed D-dimer levels were used as the dependent variable. For logistic regression, participants were dichotomized into two groups: low and elevated D-dimer levels; the latter defined as levels greater than 0.377 µg/mL (4^th quartile). Regression coefficients and OR with 95% CI were calculated to assess the contribution of predictors.
Results: Factors independently associated with higher D-dimer levels by linear regression were: female sex (+0.141, p< 0.0001), black race (+0.055, p< 0.0001), older age (+0.061 per 10 years older, p< 0.0001), being off ART at baseline (+0.075, p< 0.0001), higher viral load (+0.037 per log₁₀, p< 0.0001), CRP (+0.009 per µg/mL, p< 0.0001) and IL-6 (+0.001 per pg/mL, p< 0.0001). In contrast, higher CD4⁺ count (-0.019 per 100 cells higher, p< 0.0001) and use of PI-containing ART regimens were associated with lower D-dimer levels (Tables). Logistic regression yielded consistent results, with female sex (OR=2.36, p< 0.0001) and black race (1.82, p< 0.0001) being important predictors of elevated D-dimer levels.

Factors	Number of subjects (% of total)	D-dimer levels (µg/mL) median (IQR)	Multivariable linear regression: adjusted regression coefficients (95% CI)
Demographics
Age (per 10 years)	9,837 (100)	-	0.061 (0.053; 0.068)
Race
Black	1,912 (19.4)	0.30 (0.18-0.53)	0.055 (0.038; 0.073)
White	6,643 (67.5)	0.22 (0.15-0.34)	Ref
Gender
Female	1,961(19.9)	0.30 (0.20-0.51)	0.141(0.125; 0.157)
Male	7,876(80.1)	0.22 (0.15-0.34)	Ref
Body mass index (kg/m2)	9,837 (100)	-	0.001 (-0.000; 0.002)

[Linear regression parameter estimates (N=9,837)]

Factors	Number of subjects (% of total)	D-dimer levels (µg/mL)median (IQR)	Multivariable linear regression: adjusted regression coefficients (95% CI)
CRP (per µg/mL)	9,837 (100)	-	0.009 (0.008; 0.010)
IL-6 (per pg/mL)	9,837 (100)	-	0.001 (0.001; 0.001)

[Linear regression (inflammatory markers)]

Factors	Number of subjects (% of total)	D-dimer (µg/mL) median (IQR)	Multivariable linear regression: adjusted regression coefficients (95% CI)
CD4+ count per 100 (cells/mm3)	9,837 (100)	-	-0.019 (-0.021; -0.016)
HIV viral load, per log10 (copies/ml)	9,837(100)	-	0.037 (0.029; 0.045)
Baseline ART use
Off ART	821 (8.4)	0.34 (0.22-0.62)	0.075 (0.037; 0.114)
PI based	3,690 (37.5)	0.24 (0.16-0.36)	-0.040 (-0.070; -0.011)
NNRTI based	3,584 (36.4)	0.22 (0.15-0.35)	-0.027 (-0.057; 0.004)
PI and NNRTI	783 (8.0)	0.22 (0.15-0.33)	-0.045 (-0.082; -0.009)
NRTI only	959 (9.8)	0.26 (0.17-0.39)	Ref

[Linear regression (HIV-specific variables)]


Conclusions: Black race, female sex, older age, viral replication and inflammatory markers are independent predictors of elevated D-dimer levels during HIV infection. Baseline ART use, PI-containing regimens in particular, is associated with lower D-dimer levels, a finding possibly attributable to lower viral loads and higher CD4⁺ counts in those on ART.
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