Evaluation of Platelet Activation by HIV Protease Inhibitors – The HIV-PLA II Study
Gerrit Kann,1,* Junaid Owasil,1,* Karina Kuczka,2 Annette Haberl,1 Timo Wolf,1 Pavel Khaykin,1 Sebastian Harder,2 Christoph Stephan,1 Nils von Hentig1 1HIVCENTER, Medical HIV Treatment and Research Unit, Johann Wolfgang Goethe University Frankfurt, Frankfurt am Main, Germany; 2Pharma...
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Dove Medical Press
2021
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oai:doaj.org-article:962caca7d0c04f0db75e9266fc9947a72021-12-02T14:51:49ZEvaluation of Platelet Activation by HIV Protease Inhibitors – The HIV-PLA II Study1179-1373https://doaj.org/article/962caca7d0c04f0db75e9266fc9947a72021-08-01T00:00:00Zhttps://www.dovepress.com/evaluation-of-platelet-activation-by-hiv-protease-inhibitors--the-hiv--peer-reviewed-fulltext-article-HIVhttps://doaj.org/toc/1179-1373Gerrit Kann,1,* Junaid Owasil,1,* Karina Kuczka,2 Annette Haberl,1 Timo Wolf,1 Pavel Khaykin,1 Sebastian Harder,2 Christoph Stephan,1 Nils von Hentig1 1HIVCENTER, Medical HIV Treatment and Research Unit, Johann Wolfgang Goethe University Frankfurt, Frankfurt am Main, Germany; 2Pharmazentrum Frankfurt, Institute of Clinical Pharmacology, Johann Wolfgang Goethe University Frankfurt, Frankfurt am Main, Germany*These authors contributed equally to this workCorrespondence: Nils von HentigHIVCENTER, Medical HIV Treatment and Research Unit, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, Frankfurt am Main, 60590, GermanyTel +49-69-63017680Fax +49-69-630183442Email Hentig@em.uni-frankfurt.deBackground: 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.Keywords: HIV protease inhibitors, platelets, leucocytes, PAC-1, GIIb/IIIa-receptorKann GOwasil JKuczka KHaberl AWolf TKhaykin PHarder SStephan Cvon Hentig NDove Medical Pressarticlehiv protease inhibitorsplateletsleucocytespac-1giib/iiia-receptorImmunologic diseases. AllergyRC581-607ENHIV/AIDS: Research and Palliative Care, Vol Volume 13, Pp 789-800 (2021) |
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DOAJ |
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EN |
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hiv protease inhibitors platelets leucocytes pac-1 giib/iiia-receptor Immunologic diseases. Allergy RC581-607 |
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hiv protease inhibitors platelets leucocytes pac-1 giib/iiia-receptor Immunologic diseases. Allergy RC581-607 Kann G Owasil J Kuczka K Haberl A Wolf T Khaykin P Harder S Stephan C von Hentig N Evaluation of Platelet Activation by HIV Protease Inhibitors – The HIV-PLA II Study |
| description |
Gerrit Kann,1,* Junaid Owasil,1,* Karina Kuczka,2 Annette Haberl,1 Timo Wolf,1 Pavel Khaykin,1 Sebastian Harder,2 Christoph Stephan,1 Nils von Hentig1 1HIVCENTER, Medical HIV Treatment and Research Unit, Johann Wolfgang Goethe University Frankfurt, Frankfurt am Main, Germany; 2Pharmazentrum Frankfurt, Institute of Clinical Pharmacology, Johann Wolfgang Goethe University Frankfurt, Frankfurt am Main, Germany*These authors contributed equally to this workCorrespondence: Nils von HentigHIVCENTER, Medical HIV Treatment and Research Unit, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, Frankfurt am Main, 60590, GermanyTel +49-69-63017680Fax +49-69-630183442Email Hentig@em.uni-frankfurt.deBackground: 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.Keywords: HIV protease inhibitors, platelets, leucocytes, PAC-1, GIIb/IIIa-receptor |
| format |
article |
| author |
Kann G Owasil J Kuczka K Haberl A Wolf T Khaykin P Harder S Stephan C von Hentig N |
| author_facet |
Kann G Owasil J Kuczka K Haberl A Wolf T Khaykin P Harder S Stephan C von Hentig N |
| author_sort |
Kann G |
| title |
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_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_sort |
evaluation of platelet activation by hiv protease inhibitors – the hiv-pla ii study |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/962caca7d0c04f0db75e9266fc9947a7 |
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