modulation of monocyte activation by atorvastatin in hiv infection

Conditions: HIV Dementia

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

Keywords: hiv monocytes cd16+ statins mcp1 inflammation