Effect of Raltegravir on Endothelial Function in HIV-Infected Patients
Condition: HIV Infection; Inflammation; Cardiovascular Disease; HIV Infections
MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Cardiovascular Diseases; Inflammation
Intervention: raltegravir; Placebo
Intervention description: For patients assigned to the raltegravir group, subjects will receive raltegravir 400mg to be taken by mouth twice daily for 24 weeks in addition to taking their current HIV medication; For the patient assigned to the placebo group, subjects will take a matching placebo pill 400mg to be taken by mouth twice daily for 24 weeks in addition to taking their current HIV medication
Intervention MeSH terms: Raltegravir Potassium
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV; endothelium; inflammation; Treatment Experienced

Summary:

      Recent studies suggest that HIV patients are at increased risk for cardiovascular events;
      however, the mechanisms underlying this increased risk remain unclear. Our group was one of
      the first to demonstrate that HIV infection is independently associated with accelerated
      atherosclerosis, as measured by carotid artery-intima media thickness (IMT), and that
      HIV-associated inflammation may be driving this accelerated atherosclerosis. The mechanism by
      which HIV disease independent of any drug-specific toxicity increases the risk of
      cardiovascular disease during HAART is not known. We hypothesize that even well controlled
      HIV infection is independently associated with cardiovascular risk and that further
      decreasing HIV-associated inflammation adding newer antiretroviral agents will also decrease
      cardiovascular risk.

      We will perform a small clinical trial of approximately 50 HIV-infected patients each to
      study the relationship between HIV infection, inflammation, thrombosis, atherogenic
      lipoproteins, and measures of atherosclerosis. We propose the following specific aims: Aim 1:
      To determine the influence of traditional and novel markers of inflammation on endothelial
      function and IMT progression; Aim 2: To determine if "intensification" with raltegravir in
      subjects on long-term antiretroviral therapy with clinically undetectable HIV RNA levels will
      improve endothelial function, and to determine if this effect is mediated by alterations in
      inflammatory markers, lipoproteins and/or thrombotic factors. For Aim 2, subjects from 2
      randomized, double-blind, placebo-controlled raltegravir intensification studies will be
      asked to co-enroll in this cardiovascular study.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Stable antiretroviral therapy for at least 12 months

          2. All plasma HIV RNA levels within the past year must be below level of detection (< 50
             copies RNA/mL), although isolated single values > 50 but < 200 copies will be allowed.

          3. Screening plasma HIV RNA levels < 50 copies RNA/mL

          4. >90% adherence to therapy within the preceding 30 days, as determined by self-report

          5. Females of childbearing potential must have a negative serum pregnancy test at
             screening and agree to use a double-barrier method of contraception throughout the
             study period.

          6. CD4<350 cells/mm3 for at least one year ("immunologic non-responder") or CD4>=350
             cells/mm3 for at least one year ("immunologic responder").

        Exclusion Criteria:

          1. Ongoing or prior use of any integrase inhibitor or R5 inhibitor.

          2. Patients who plan to modify existing antiretroviral therapy in the next 24 weeks for
             any reason

          3. Serious illness requiring hospitalization or parental antibiotics within preceding 3
             months

          4. Concurrent or recent exposure to any immunomodulatory drugs

          5. Advanced liver disease or active hepatitis B or C

          6. Patients with systolic blood pressure <100/70

          7. Starting or stopping statin therapy during the trial