Modulation of Monocyte Activation by Atorvastatin in HIV Infection
Condition: HIV Dementia
MeSH terms: AIDS Dementia Complex
Intervention: Atorvastatin
Intervention description: For subjects on PI-based HAART therapy: 10mg/day X 2weeks followed by 20mg/day.
For subjects on non PI-based HAART therapy: 20mg/day X 2weeks followed by 40mg/day.
Intervention MeSH terms: Atorvastatin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV; monocytes; CD16+; statins; mcp1; inflammation

Summary:

      Activated monocytes play a key role in the pathogenesis of HIV-associated neurocognitive
      disorders (HAND). Individuals with HAND have expanded populations of activated monocytes.
      These monocytes are thought to emigrate into the CNS, where they produce neurotoxic
      proinflammatory factors, and also carry virus into the CNS. Statins are cholesterol lowering
      drugs with pleiotropic immunomodulatory / anti-inflammatory properties that are currently
      being explored for immunomodulation of T cell activation in several diseases, in addition to
      their established role to treat hyperlipidemia and atherosclerosis. The investigators in
      vitro data suggests that these drugs can downregulate monocyte activation patterns seen in
      HIV infection. No in vivo studies have yet been carried out to assess the effects of statins
      on the pro-inflammatory monocyte population in chronic HIV disease. This will be a pilot
      study of whether statin treatment will reduce the inflammatory monocyte phenotype and
      downregulate the inflammatory cytokines that have been linked to neuropathogenesis in HIV
      infection. If so, they may have potential as adjunctive therapy in HIV-associated
      neurological disease. The investigators propose to:

        -  Determine the effect of Atorvastatin on peripheral blood monocyte populations in a
           12-week pilot study in chronically HIV-infected people on HAART therapy.

        -  Determine the relationship between changes in monocyte phenotype following Atorvastatin
           treatment, and soluble markers of activation/inflammation linked to neuropathogenesis,
           as well as activation status of T cells.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Chronic HIV-1 infected individuals presently on HAART with no change in drug
             combination for at least 3 months at time of enrollment

          2. Plasma viral load <200 copies / ml for at least 6 months prior to enrollment in the
             study

          3. CD4 T cell count more than 350/ul

          4. Willingness to use a method of contraception during the study period

          5. Willingness to have blood drawn

          6. If female, willingness to undergo pregnancy testing on a monthly basis and are not
             breastfeeding

          7. Ability to understand and willingness to sign the informed consent

          8. hs-CRP levels above the upper limit of normal (>3mg/L)

        Exclusion Criteria:

          1. Concomitant use of fibric acid derivatives or other lipid lowering agents including
             patients on statins and Ezetimibe

          2. Use of any anti-inflammatory drugs (OTC or prescription) on a daily basis

          3. Pregnancy or breast feeding

          4. Active drug use or alcohol abuse/dependence, which in the opinion of the investigators
             will interfere with the patient's ability to participate in the study

          5. Allergy or hypersensitivity to statins or any of its components

          6. History of myositis or rhabdomyolysis with use of any statins

          7. Patients who are on concurrent immunomodulatory agents, including systemic
             corticosteroids will be ineligible for 3 months after completion of therapy with the
             immunomodulating agents

          8. History of inflammatory muscle disease such as poly or dermatomyositis

          9. Serious intercurrent illness requiring systemic treatment and/or hospitalization
             within 30 days of entry

         10. Evidence of active opportunistic infections requiring treatment or neoplasms that
             require chemotherapy during the study period

         11. Creatine phosphokinase elevations (CPK) greater than 3 times the upper limit of normal

         12. Known active liver disease or AST/ALT greater than 2x the upper limit of normal

         13. Renal insufficiency, indicated by serum creatinine 2 mg/dl

         14. Absolute neutrophil count (ANC) 1000/mm3, hemoglobin < 10.0 g/dL for males and <9 g/dL
             for females, platelet count 100,000/mm