Thromboelastography on plasma reveals delayed clot formation and accelerated clot lyses in HIV-1 infected persons compared with healthy controls

BACKGROUND: Thromboembolic events among HIV infected persons are a recognized clinical problem but the underlying mechanisms are poorly understood. To assess whether coagulation and fibrinolysis differ between long-term treated HIV infected individuals (HIV+) and healthy controls (CON), we investigated functional plasma coagulation by thrombelastography (TEG) and plasma markers of endothelial and platelet activation. METHODS: In 67 successfully long-term treated HIV+ and 15 CON we analyzed stored plasma samples by TEG, with or without addition of tissue-type plasminogen activator (tPA), and measured levels of C-reactive protein, thrombomodulin, syndecan-1, sVE-cadherin, soluble CD40 ligand (sCD40L), adrenaline and noradrenaline. RESULTS: Compared to CON, HIV+ had delayed clot formation (reaction (R)-time 14.2 min. vs. 11.2 min., p = 0.0004) and reduced clot formation rapidity (angle 22.6° vs. 48.6 °, p = <0.0001). Clot lyses induced by tPA was accelerated in HIV+ displaying enhanced clot degradation after 30 and 60 min (53.9 % vs. 24.2 %, p < 0.0001 and 77.4 % vs. 59.9 %, p < 0.0001, respectively). sCD40L and TEG R-time correlated negatively in both HIV+ and CON (Rho =−0.502, p < 0.001 and rho =−0.651, p = 0.012). DISCUSSION: No previous studies have examined plasma coagulation by TEG in HIV, however, we have previously demonstrated that HIV+ display hypocoagulability in whole blood by TEG in accordance with the results of this study. Others have reported of HIV associated changes in the hemostatic system in a pro-coagulant direction based on measurements of isolated components of the coagulation pahways. In disease conditions, the flowing blood may change from “normal” to hyper- or hypocoagulant or to hyper- or hypofibrinolytic. A balance may exist in the flowing blood, i.e. between blood cells and the plasma phase, so that pro-coagulant blood cells are balanced by a hypocoagulable plasma phase; thus alterations that may promote thromboembolic events in the patient may at the same time appear as a hypocoagulable profile when evaluated in vitro. CONCLUSION: Plasma from long-term treated HIV infected persons displays a hypocoagulable profile with reduced fibrinolytic resistance as compared to healthy controls

Kaplan-Meier plots.

<p>The observation period (days) is from 18 months (+/−6 months) after initiation of cART till death or 01/01/2010. The dotted line depicts the highest 50^th percentile and the full line depicts the lowest 50^th percentile. Analysis of survival linked to T cell subset are made with proportions of CD4+ and CD8+ cells respectively. Analysis using concentrations instead of proportions yielded similar results. Subsets were defined as naïve CD4/8(CD45RA+, CD62+), memory CD4/8 (CD45RA-, CD45R0+) and activated CD4 (HLA-DR+), and activated CD8 (HLA-DR+, CD38+).</p

Uni-and multivariate cox regression.

<p>The analysis only included subjects with complete data (N = 90).</p><p>HR: hazard ratio, CI: confidence interval, %: proportion of total CD4 or CD8 cells respectively.</p><p>Subsets were defined as naïve CD4/8(CD45RA+, CD62+), memory CD4/8 (CD45RA-, CD45R0+), activated CD4 (HLA-DR+), and activated CD8 (HLA-DR+, CD38+).</p

Additional file 3: of Persistence of cervical high-risk human papillomavirus in women living with HIV in Denmark â the SHADE

Unadjusted and adjusted odds ratios for predictors of low-grade squamous intraepithelial lesions or worse (LSIL+). A table presenting the unadjusted and adjusted odds ratios for predictors of low-grade squamous intraepithelial lesions or worse (LSIL+). (DOCX 17 kb

Additional file 2: of Persistence of cervical high-risk human papillomavirus in women living with HIV in Denmark â the SHADE

Unadjusted and adjusted odds ratios for predictors of atypical cells of undetermined significance or worse (ASCUS+). A table presenting the unadjusted and adjusted odds ratios for predictors of atypical cells of undetermined significance or worse (ASCUS+). (DOCX 18 kb

Additional file 1: of Persistence of cervical high-risk human papillomavirus in women living with HIV in Denmark â the SHADE

Questionnaire at visit 1 (inclusion). A questionnaire regarding information on tobacco use, age at sexual debut, lifetime sexual partners, prior condyloma, HPV vaccination status, and contraceptive use. (DOC 127 kb

Additional file 4: of Persistence of cervical high-risk human papillomavirus in women living with HIV in Denmark â the SHADE

Unadjusted and adjusted odds ratios for predictors of high-grade squamous intraepithelial lesions or worse (HSIL+). A table presenting the Unadjusted and adjusted odds ratios for predictors of high-grade squamous intraepithelial lesions or worse (HSIL+). (DOCX 18 kb

Persistence of cervical high-risk human papillomavirus in women living with HIV in Denmark – the SHADE

Abstract Background Women living with HIV (WLWH) have high rates of persistent high-risk human papillomavirus (hrHPV) infections and cervical cancer. We aimed to assess the distribution of hrHPV genotypes, risk factors of type-specific hrHPV persistence, and high-grade squamous intraepithelial lesions or worse (≥HSIL) in WLWH in Denmark. Methods From the prospective Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) we identified WLWH with a positive hrHPV test during the study period; 2011–2014. HIV demographics were retrieved from the Danish HIV Cohort Study and pathology results from the The Danish Pathology Data Bank. Logistic regression was used to identify risk factors associated with persistent hrHPV infection (positivity of the same hrHPV type in two samples one-two years after the first hrHPV positive date) and ≥ HSIL. Results Of 71 WLWH, 31 (43.7%) had persistent hrHPV infection. Predominant hrHPV genotypes were HPV58, 52, 51, and 35 and most frequently observed persistent genotypes were HPV52, 33 and 31. CD