Modulation of Monocyte Activation by Atorvastatin in HIV Infection
| Status: | Completed |
|---|---|
| Conditions: | HIV / AIDS, Neurology |
| Therapuetic Areas: | Immunology / Infectious Diseases, Neurology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 12/14/2017 |
| Start Date: | September 2011 |
| End Date: | October 2017 |
Pilot Study to Evaluate Effects of Atorvastatin on Monocyte Activation in HAART-treated HIV Infected Individuals
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.
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.
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
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