Effects of Raltegravir Based Regimen on Platelet Reactivity, Platelet-monocyte Aggregation and Immune Activation

• Status: Completed
• Trial end date: 2017-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Cardiovascular disease (CVD) has emerged as a leading cause of morbidity and mortality in HIVinfected individuals. The precise mechanisms underlying this increased cardiovascular risk remain to be elucidated. Platelet hyperreactivity and increased platelet-monocyte aggregation (PMA) are found in HIVinfectedpatients and may contribute to the excess cardiovascular risk as platelets play a key role in the onset and progression of atherosclerosis and in acute cardiovascular events. In addition, HIV-infected individuals frequently suffer from persistent immune activation and inflammation. In a crosssectional study the investigators recently showed that individuals using a regimen containing the integrase inhibitor raltegravir have reduced platelet hyperreactivity and PMA compared to other antiretroviral regimens. Other recent studies showed that raltegravir is associated with decreased immune activation. Due to the inherent limitations of cross sectional studies, the investigators aim to expand our findings in an intervention study. The investigators will conduct a randomized control trial where the investigators switch patients to a integrase containing treatment regimen to assay possible changes in platelet function and persistent immune activation. Knowledge gathered in the proposed study can help understand and prevent cardiovascular disease in patients treated for a HIV infection by reducing platelet hyperreactivity and persistent immune activation.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Radboud University
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Raltegravir Potassium

Criteria

Inclusion Criteria:

• Male or female

• Documented HIV-infection

• Age ≥ 18 years

• Willing to comply with the protocol requirements

• 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 adenosine diphosphate (ADP) receptor antagonists

• Known hypersensitivity to raltegravir or any other component of the formulation

• Using any concomitant therapy disallowed as per summary of product characteristics (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

• Clinical or laboratory evidence of significantly decreased hepatic function, defined as alanine aminotransferase (ALAT) level > 2 upper limit of normal (ULN)

• History of suspected or proven virologic failure since ART initiation (HIV-1 RNA "blips" less than 500 copies per milliliter with subsequent suppression are allowed)

• Known genotypic resistance to any current ART component

• Prior use of single or dual NRTI-only regimens, or history of any ART not considered highly active by current standards.

• In females, pregnancy or breast feeding