Research ArticleHEALTH AND MEDICINE

Targeting thrombogenicity and inflammation in chronic HIV infection

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Science Advances  12 Jun 2019:
Vol. 5, no. 6, eaav5463
DOI: 10.1126/sciadv.aav5463
  • Fig. 1 Blood thrombogenicity.

    (A) Thrombus formation at low shear rate (top) and high shear (bottom) rate in PWH versus age- and sex-matched seronegative controls. (B) Thrombus formation at low and high shear rates in PWH versus seronegative controls, separated by gender.

  • Fig. 2 Correlations of thrombus size with markers of inflammation.

    Thrombus formation at high shear rate showed strong correlation with sTNFR1, sTNFR2, and nonclassical monocytes and a strong negative correlation with classical monocytes, tested using Pearson’s correlation.

  • Fig. 3 Effects of antiplatelet treatments on thrombogenicity and inflammation.

    (A) Thrombus formation at low and high shear rates in PWH treated with study drugs, at baseline (0) and after 24 weeks. (B) sCD14 levels measured in study groups at baseline (0) and 12 and 24 weeks of study treatment.

  • Fig. 4 Study design.

    Flow chart of the study design showing the cross-sectional, case-control study in the top part and the randomized, double-blind pilot trial in the bottom part. BT, blood thrombogenicity; TK, thrombus kinetics; PR, platelet reactivity; MoI, markers of inflammation.

  • Table 1 Baseline demographics of study participants.

    LDL, low-density lipoprotein; HDL, high-density lipoprotein; NSTI, integrase strand transfer inhibitors; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; pi, protease inhibitor.

    Seronegative
    controls (n = 14)
    PWH (n = 15)
    Age (years)44 (21)46 (13)
    Male, no. (%)7 (50%)8 (53%)
    Race
      White non-Hispanic5 (35.5%)3 (20.0%)
      Black non-Hispanic4 (29.0%)6 (40.0%)
      Hispanic5 (35.5%)6 (40.0%)
    Body mass index (kg/m2)25.6 (2.5)27.9 (10.7)
    CD4 T cell count708 (380)
    Smoking
      Never11 (78.6%)7 (46.7%)
      Past1 (7.1%)4 (26.7%)
      Current2 (14.3%)4 (26.7%)
    ART, no. (%)
      Abacavir-based2 (13.0%)
      INSTI + 2 NRTI6 (40.0%)
      NNRTI + 2 NRTI2 (13.0%)
      PI + 2 NRTI6 (40.0%)
    LDL (mg/dl)114 (30)99 (21)
    HDL (mg/dl)52 (20)47 (22)
    Total cholesterol (mg/dl)181 (53)169 (55)
    Platelet count (×109/liter)221 (95)232 (124)
  • Table 2 Platelet reactivity of PWH versus seronegative controls.

    Maximum platelet aggregation in response to various agonists tested using platelet aggregometry and summarized as median (IQR).

    Seronegative
    controls
    (n = 14)
    PWH (n = 15)P
    Spontaneous
    aggregation
    2.0 (2.3)3.0 (1.0)0.008
    ADP
      0.4 μM5.0 (10.8)5.0 (5.0)0.946
      1.0 μM18.0 (24.5)14.5 (9.8)0.701
      20 μM85.5 (13.3)84.0 (19.8)0.701
    Arachidonic acid
      150 μM1.0 (2.5)3.0 (4.5)0.133
      500 μM73.0 (22.0)86.5 (14.8)0.013
    Collagen
      0.05 μg/ml2.0 (2.0)3.0 (5.0)0.019
      2.0 μg/ml82.5 (15.3)78.0 (17.0)0.571
    Epinephrine
      0.0 5 μM5.5 (17.5)5.5 (5.3)0.635
      0.1 μM7.0 (49.8)6.5 (6.5)0.701
      5.0 μM82.5 (22.0)88.0 (39.0)0.488

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/5/6/eaav5463/DC1

    Table S1. Thrombus size [median (IQR) μm2/mm] of PWH versus seronegative controls: Subgroup analyses.

    Table S2. Coagulation parameters [median (IQR)] of PWH versus seronegative controls: Gender analyses.

    Table S3. Correlation of high-shear thrombus with parameters of inflammation and thrombosis in PWH versus seronegative controls.

  • Supplementary Materials

    This PDF file includes:

    • Table S1. Thrombus size median (IQR) μm2/mm of PWH versus seronegative controls: Subgroup analyses.
    • Table S2. Coagulation parameters median (IQR) of PWH versus seronegative controls: Gender analyses.
    • Table S3. Correlation of high-shear thrombus with parameters of inflammation and thrombosis in PWH versus seronegative controls.

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