Elite Controller and ART-treated HIV+ Statin Versus ASA Treatment Intervention Study
Condition: Human Immunodeficiency Virus
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Intervention: Aspirin; Atorvastatin
Intervention description: Daily Asprin daily; Daily Atorvastatin Daily
Intervention MeSH terms: Aspirin; Atorvastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Treated Progressors; Immune Activation

Summary:

      Background:

      - The immune system protects the body from infection. But it can also cause harm. For
      example, the clotting system makes blood clot and protects from bleeding. But blood clots are
      sometimes harmful. People with human immunodeficiency virus (HIV) infection have increased
      inflammation and clotting. This may increase their risk for diseases like stroke or heart
      attack. Researchers want to know how aspirin or HMG-CoA reductase inhibitors (so-called
      statin medications) affect the immune and clotting systems of people with HIV. Aspirin is a
      medicine to decrease clotting. Statins are medications given to lower cholesterol and
      decrease inflammation.

      Objectives:

      - To see how aspirin or statins change immune and clotting systems in people with HIV.

      Eligibility:

      - Adults 18 and older with HIV and a low viral load, not on aspirin or a statin medication.
      They must also have either: (1) never taken anti-HIV medications (ARVs), have a suppressed
      viral load, have stable CD4 counts, and never had an opportunistic infection; or (2) been
      taking ARVs for 5 continuous years and have a suppressed viral load for more than 3 years.

      Design:

        -  Participants will be screened with medical history, physical exam, and blood and lab
           tests.

        -  Participants will repeat screening tests and have an MRI. An MRI is a way to visualize
           blood vessels in the neck and head. Participants will lie on a table that slides in and
           out of a cylinder surrounded by a magnetic field.

        -  Participants will take either study drug once daily for 9 months.

        -  Participants will have a blood procedure twice. Blood will be removed through a needle
           in one arm and circulated through a machine that removes white blood cells. The blood,
           minus white blood cells, is returned through a needle in the other arm.

        -  All participants will be observed for 3 months before and after treatment.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        EC Arm

          1. Age greater than or equal to 18 years.

          2. Documented HIV-1 infection confirmed by enzyme-linked immunosorbent assay (ELISA) and
             Western blot tests (will not be repeated if performed previously at NIH).

          3. Categorized as a long term non-progressor EC as defined by viral loads typically less
             than the LLD of commercially available assays and clinical and laboratory criteria (no
             OIs, no ART, stable CD4 T cell counts for more than 3 years). Viral load blips are
             allowed as long as they are less than 500 copies/mL and flanked by viral load
             measurements less than 100copies/mL. Viral load <100c/mL will be acceptable for
             eligibility at screening.

          4. In women of childbearing potential, with no plans for pregnancy for the next 15 months
             and willing to use 2 investigator approved highly reliable methods of birth control
             consistently while on the study or in 3 month follow up.

          5. Willingness to have samples stored for future research.

          6. Not on a statin or ASA for the past 6 months.

        ART <50 Arm

          1. Age greater than or equal to 18 years.

          2. Documented HIV-1 infection confirmed by enzyme-linked immunosorbent assay (ELISA) and
             Western blot tests.

          3. In women of childbearing potential, with no plans for pregnancy for the next 15 months
             and willing to use 2 investigator approved highly reliable methods of birth control
             consistently while on the study or in 3 month follow up.

          4. On continuous combination ART >4 years.

          5. HIV RNA <50 copies/mL (or less than 40 or less than 48 copies/mL, depending on the
             lower limit of detection of the assay used; transient periods of low level (<300)
             detectable virus, blips, acceptable if isolated and followed by viral loads less than
             the lower limit of detection) >3 years and current HIV-RNA less than the LLD of the
             commercially available assay used. Subject will be rescreened if HIV is detectable at
             screening visit.

          6. Willingness to have samples stored for future research.

          7. Not on a statin or ASA for the past 6 months.

        EXCLUSION CRITERIA

          1. Diagnosis of cardiovascular disease or hypercholesterolemia (LDL cholesterol 190
             mg/dL).

          2. Known hypersensitivity or allergy to ATV or ASA, including a history of myositis or
             rhabdomyolysis with statin or ASA use.

          3. Other contraindication for ASA or statin therapy (active liver disease, peptic ulcer
             disease, etc.).

          4. Women who are lactating, pregnant, or actively trying to become pregnant or
             considering pregnancy over the likely span of the study (including women of
             childbearing potential who are unwilling to use adequate contraception throughout the
             study).

          5. Any chronic inflammatory condition either requiring anti-inflammatory medication
             (systemic corticosteroids, daily NSAID use,immunomodulating medications) which may, in
             the opinion of the investigator, confound the interpretation of soluble inflammatory
             biomarkers. While on study, short term (less than 5 days) NSAID use will be allowed at
             the discretion of the investigator.

          6. Active drug use or alcohol abuse that, in the opinion of the investigator, may
             interfere with the ability of the subject to participate in the study or that may
             unacceptably increase the risk of the study intervention..

          7. Safety laboratory cut offs: coagulation (INR >2 upper limit of normal [ULN], PLT<75K),
             renal function (GFR<60), liver function (ALT or Alkaline phosphatase or direct
             bilirubin >2x ULN), aldolase <1.5 ULN and anemia (Hg <9 mg/dL).

          8. Antiretroviral therapy with tipranivir, or any therapy which combines non-nucleoside
             reverse transcriptase inhibitors with protease inhibitors.

          9. Chronic hepatitis C co-infection. However, if a subject has more than 24 weeks of
             sustained virologic response (SVR), the subject can be considered for eligibility.

         10. If either MR or apheresis is contraindicated, subject may still participate without
             this procedure. In the case of missed apheresis, a 30 mL research blood draw will be
             substituted (see Appendices B and C).

               -  If statin initiation is indicated per current guidelines, subject will be
                  counseled to consult with their PMD. If the subject then chooses to take part in
                  the study, we will provide their PMD with all pertinent lab results during the
                  course of the study, if requested.

        Co-enrollment Guidelines: Co-enrollment in other trials will be restricted, other than
        enrollment on observational studies. Study staff should be notified of co-enrollment as it
        may require the approval of the Investigator.