Switch from a NNRTI or PI-based regimen to a RAltegravir-based regimen in virologically suppressed HIV-infected patients: effects on Platelet reactivity, platelet-monocyte aggregation and the Inflammatory anD thrombotic state of monocytes

Completed

• Conditions: human immunodeficiency virus (HIV); 10047438

• Registration Number: NL-OMON42115
• Lead Sponsor: Radboudumc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 40

Inclusion Criteria

•Documented HIV-infection
•Age >= 18 years
•On stable antiretroviral therapy (ART) for >= 6 months at screening
•Undetectable plasma HIV viral load (<50 copies/mL) for at least 6 months
•CD4 cell count > 300 cells/mm3 at last measurement
•Current ART regimen at screening consisting of a 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) and on this regimen for > 3 months
•If female and of childbearing potential using effective birth control methods

Exclusion Criteria

•Use of platelet function inhibitors, such as aspirin and ADP receptor antagonists
•Known hypersensitivity to raltegravir or any other component of the formulation
•Using any concomitant therapy disallowed as per SPC for the study drug
•Signs of symptoms of an active (opportunistic) infection other than HIV
•Active hepatitis B or C
•Estimated glomerular filtration rate (by MDRD) <50 ml/min
•History of suspected or proven virologic failure since ART initiation (HIV-1 RNA *blips* less than 500 copies per milliliter with subsequent resuppression are allowed)
•Known genotypic resistance to any current ART component
•In females, pregnancy or breast feeding

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>1. Platelet reactivity: platelet expression of the platelet activation marker<br /><br>CD62P (P-selectin) and activated fibrinogen receptor (aIIb&beta;3) upon stimulation<br /><br>with different platelet agonists. 2. Platelet-leukocyte aggregates (eg. PMA).<br /><br>3. Proportion of CD14+CD16 ++(bright) monocytes compared to CD14+CD16- and<br /><br>activation state of monocytes (CD11b expression) and lymphocytes (CD38+ HLA-DR+<br /><br>CD8+ T cells). 4. Soluble (plasma) markers of platelet and monocyte<br /><br>activation.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Investigate whether switch to raltegravir is associated with:<br /><br>a) reduced activation status of monocytes and of CD4 and CD8 lymphocytes<br /><br>b) reduced expression of CCR5 on monocytes and CD4+ T-lymphocytes<br /><br>c) reduced plasma levels of inflammatory markers (eg. hs-CRP, several cytokines)<br /><br>d) epigenetic changes (eg. Histone methylation)<br /><br>e) altered IL-32 expression and splicing</p><br>