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 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.

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Author:Gerrit KannGND, Junaid OwasilGND, Karina Maria KuczkaGND, Annette Haberl, Timo WolfORCiDGND, Pavel Khaykin, Sebastian HarderGND, Christoph StephanORCiDGND, Nils von HentigORCiDGND
Parent Title (English):HIV/AIDS : research and palliative care
Publisher:Dove Medical Press
Place of publication:Macclesfield [u.a.]
Document Type:Article
Date of Publication (online):2021/08/06
Date of first Publication:2021/08/06
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/10/24
Tag:GIIb/IIIa-receptor; HIV protease inhibitors; PAC-1; leucocytes; platelets
Page Number:12
First Page:789
Last Page:800
The authors are grateful for the support of this study provided by the Fritz- und Heinrich Riese Foundation.
Institutes:Biochemie, Chemie und Pharmazie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 3.0