HIV infection is associated with platelet hyperreactivity and increased platelet-monocyte aggregation (PMA), which may contribute to the excess cardiovascular risk. In a cross-sectional study we recently showed that individuals using a raltegravir-based regimen have reduced platelet reactivity and PMA compared to other antiretroviral regimens. The aim of this study was to investigate whether switching a non-nucleoside reverse transcriptase inhibitor (NNRTI)- or protease inhibitor (PI)-based regimen to a raltegravir-based regimen reduces platelet reactivity and/or PMA.
This study was designed as an investigator initiated, single-center, prospective randomized, open-label, blinded endpoint (PROBE) trial. We enrolled 40 adult HIV-infected individuals with undetectable (<40 copies/mL) viral load receiving a standard backbone of two NRTI’s (either TDF/FTC or ABC/3TC) with either a NNRTI (EFV or RPV) or a boosted PI (DRV/r, ATZ/r or LPV/r). Participants were randomized (1:1) to continue the same ART regimen or to switch to raltegravir during 3 months. The primary outcome was the change (Δ) in platelet reactivity at 3 months. This was determined using a flow-cytometry based assay by measuring platelet expression of the platelet granule protein P-selectin and the binding of fibrinogen to the activated αIIbβ3 integrin upon ex vivo stimulation of whole blood with three different platelet agonists (ADP, collagen-related-peptide and thrombin receptor activator peptide). Plasma markers of platelet activation (platelet factor-4, beta-thromboglobulin and P-selectin) and inflammation (high-sensitive C-reactive protein (hs-CRP) were also measured. Analysis was based on intention-to-treat using an unpaired t-test or Mann-Whitney test. Clinicaltrials.gov identifier: NCT02383355.
The groups were well matched. Overall, 95% of participants were male with a median age of 48yrs, and a median CD4 count of 660 cells/µL. No Grade III-IV adverse events were recorded. At 3 months, the Δ platelet reactivity, to all three platelet agonists, were similar between the two groups. Neither PMA formation nor plasma levels of platelet factor-4, beta-thromboglobulin and soluble P-selectin were different between groups. In addition, plasma hsCRP did not differ between treatments at 3 months.
A switch to a raltegravir-based regimen in virally suppressed HIV-infected individuals reduces neither platelet reactivity nor platelet-monocyte aggregation.