TY  - JOUR
A1  - Kann, Gerrit
A1  - Owasil, Junaid
A1  - Kuczka, Karina Maria
A1  - Haberl, Annette
A1  - Wolf, Timo
A1  - Khaykin, Pavel
A1  - Harder, Sebastian
A1  - Stephan, Christoph
A1  - Hentig, Nils von
T1  - Evaluation of platelet activation by HIV protease inhibitors – the HIV-PLA II study
T2  - HIV/AIDS : research and palliative care
N2  - 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.
KW  - HIV protease inhibitors
KW  - platelets
KW  - leucocytes
KW  - PAC-1
KW  - GIIb/IIIa-receptor
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/69266
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-692669
SN  - 1179-1373
N1  - The authors are grateful for the support of this study provided by the Fritz- und Heinrich Riese Foundation.
VL  - 13
SP  - 789
EP  - 800
PB  - Dove Medical Press
CY  - Macclesfield [u.a.]
ER  -