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Evaluation of Platelet Activation by HIV Protease Inhibitors – The HIV-PLA II Study
BACKGROUND: In the past, protease inhibitors (PIs) and the reverse transcriptase inhibitor abacavir were identified increasing the risk for thromboembolic complications and cardiovascular events (CVE) of HIV infected patients taking a combination antiretroviral therapy (cART). Results of the previou...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354741/ https://www.ncbi.nlm.nih.gov/pubmed/34393518 http://dx.doi.org/10.2147/HIV.S262282 |
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author | Kann, Gerrit Owasil, Junaid Kuczka, Karina Haberl, Annette Wolf, Timo Khaykin, Pavel Harder, Sebastian Stephan, Christoph von Hentig, Nils |
author_facet | Kann, Gerrit Owasil, Junaid Kuczka, Karina Haberl, Annette Wolf, Timo Khaykin, Pavel Harder, Sebastian Stephan, Christoph von Hentig, Nils |
author_sort | Kann, Gerrit |
collection | PubMed |
description | BACKGROUND: In the past, protease inhibitors (PIs) and the reverse transcriptase inhibitor abacavir were identified increasing the risk for thromboembolic complications and cardiovascular events (CVE) of HIV infected patients taking a combination antiretroviral therapy (cART). Results of the previous HIV-PLA I-study lead to the assumption that platelet activation could play a substantial role in increasing CVE risks. METHODS: The open label, monocentric HIV-PLA II-study investigated HIV-1-infected, therapy-naïve adults (n=45) starting with cART, consisting either of boosted PI (atazanavir, n= 6, darunavir, n=11), NNRTI (efavirenz, n=14) or integrase inhibitor (raltegravir, n=14), each plus tenofovir/emtricitabine co-medication. Main exclusion criteria were tobacco smoking, the intake of NSAIDs or abacavir or past CVE. Platelet adhesive molecule p-selectin (CD62P) and FITC anti-human Integrin α-IIb/Integrin β-3 (CD41/CD61) antibody (PAC-1) binding, monocyte CD11b/monocyte-associated CD41 expression and the endogenous thrombin potential (ETP) were assessed ex vivo-in vitro at baseline, weeks 4, 12 and 24. Therapy regimens were blinded to the investigators for laboratory and statistical analyses. RESULTS: CD11b and ETP showed no significant changes or differences between all study groups. In contrast, the mean + SD mean fluorescence units (MFI) of CD62P and PAC-1 increased significantly in patients taking PI, indicating an enhanced potential for thrombocyte activation and aggregation. CONCLUSION: CD62P expression, detecting the ɑ-platelet degranulation of pro-inflammatory and pro-thrombotic factors and adhesive proteins, and PAC-1 expression, representing a marker for conformation changes of the GIIb/IIIa receptor, increased significantly in patients taking HIV protease inhibitors. The findings of this study revealed a yet unknown pathway of platelet activation, possibly contributing to the increased risk for CVE under HIV protease inhibitor containing cART. CLINICAL TRIAL REGISTRATION NO. DRKS00000288. |
format | Online Article Text |
id | pubmed-8354741 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-83547412021-08-12 Evaluation of Platelet Activation by HIV Protease Inhibitors – The HIV-PLA II Study Kann, Gerrit Owasil, Junaid Kuczka, Karina Haberl, Annette Wolf, Timo Khaykin, Pavel Harder, Sebastian Stephan, Christoph von Hentig, Nils HIV AIDS (Auckl) Original Research BACKGROUND: In the past, protease inhibitors (PIs) and the reverse transcriptase inhibitor abacavir were identified increasing the risk for thromboembolic complications and cardiovascular events (CVE) of HIV infected patients taking a combination antiretroviral therapy (cART). Results of the previous HIV-PLA I-study lead to the assumption that platelet activation could play a substantial role in increasing CVE risks. METHODS: The open label, monocentric HIV-PLA II-study investigated HIV-1-infected, therapy-naïve adults (n=45) starting with cART, consisting either of boosted PI (atazanavir, n= 6, darunavir, n=11), NNRTI (efavirenz, n=14) or integrase inhibitor (raltegravir, n=14), each plus tenofovir/emtricitabine co-medication. Main exclusion criteria were tobacco smoking, the intake of NSAIDs or abacavir or past CVE. Platelet adhesive molecule p-selectin (CD62P) and FITC anti-human Integrin α-IIb/Integrin β-3 (CD41/CD61) antibody (PAC-1) binding, monocyte CD11b/monocyte-associated CD41 expression and the endogenous thrombin potential (ETP) were assessed ex vivo-in vitro at baseline, weeks 4, 12 and 24. Therapy regimens were blinded to the investigators for laboratory and statistical analyses. RESULTS: CD11b and ETP showed no significant changes or differences between all study groups. In contrast, the mean + SD mean fluorescence units (MFI) of CD62P and PAC-1 increased significantly in patients taking PI, indicating an enhanced potential for thrombocyte activation and aggregation. CONCLUSION: CD62P expression, detecting the ɑ-platelet degranulation of pro-inflammatory and pro-thrombotic factors and adhesive proteins, and PAC-1 expression, representing a marker for conformation changes of the GIIb/IIIa receptor, increased significantly in patients taking HIV protease inhibitors. The findings of this study revealed a yet unknown pathway of platelet activation, possibly contributing to the increased risk for CVE under HIV protease inhibitor containing cART. CLINICAL TRIAL REGISTRATION NO. DRKS00000288. Dove 2021-08-06 /pmc/articles/PMC8354741/ /pubmed/34393518 http://dx.doi.org/10.2147/HIV.S262282 Text en © 2021 Kann et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Kann, Gerrit Owasil, Junaid Kuczka, Karina Haberl, Annette Wolf, Timo Khaykin, Pavel Harder, Sebastian Stephan, Christoph von Hentig, Nils Evaluation of Platelet Activation by HIV Protease Inhibitors – The HIV-PLA II Study |
title | Evaluation of Platelet Activation by HIV Protease Inhibitors – The HIV-PLA II Study |
title_full | Evaluation of Platelet Activation by HIV Protease Inhibitors – The HIV-PLA II Study |
title_fullStr | Evaluation of Platelet Activation by HIV Protease Inhibitors – The HIV-PLA II Study |
title_full_unstemmed | Evaluation of Platelet Activation by HIV Protease Inhibitors – The HIV-PLA II Study |
title_short | Evaluation of Platelet Activation by HIV Protease Inhibitors – The HIV-PLA II Study |
title_sort | evaluation of platelet activation by hiv protease inhibitors – the hiv-pla ii study |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354741/ https://www.ncbi.nlm.nih.gov/pubmed/34393518 http://dx.doi.org/10.2147/HIV.S262282 |
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