Effects of Raltegravir Based Regimen on Platelet Reactivity, Platelet-monocyte Aggregation and Immune Activation
Condition: HIV
Intervention: Raltegravir; Continuation of own regimen
Intervention description: Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy; Continuation of own antiretroviral medication during the 10 weeks follow-up
Intervention MeSH terms: Raltegravir Potassium
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Persistent immune activation; Platelet hyperreactivity

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.
    

Eligibility 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