- 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.
MetadatenAuthor: | Gerrit KannGND, Junaid OwasilGND, Karina Maria KuczkaGND, Annette Haberl, Timo WolfORCiDGND, Pavel Khaykin, Sebastian HarderGND, Christoph StephanORCiDGND, Nils von HentigORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-692669 |
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DOI: | https://doi.org/10.2147/HIV.S262282 |
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ISSN: | 1179-1373 |
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Parent Title (English): | HIV/AIDS : research and palliative care |
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Publisher: | Dove Medical Press |
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Place of publication: | Macclesfield [u.a.] |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2021/08/06 |
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Date of first Publication: | 2021/08/06 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2023/10/24 |
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Tag: | GIIb/IIIa-receptor; HIV protease inhibitors; PAC-1; leucocytes; platelets |
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Volume: | 13 |
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Page Number: | 12 |
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First Page: | 789 |
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Last Page: | 800 |
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Note: | The authors are grateful for the support of this study provided by the Fritz- und Heinrich Riese Foundation. |
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HeBIS-PPN: | 515016845 |
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Institutes: | Biochemie, Chemie und Pharmazie |
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| Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell 3.0 |
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