Modulation of Monocyte Activation by Atorvastatin in HIV Infection

University of Pennsylvania

Status and phase

Completed

Phase 4

Conditions

HIV Dementia

Treatments

Drug: Atorvastatin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01263938

IRB Protocol #: 812196

P30AI045008 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment

5 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Chronic HIV-1 infected individuals presently on HAART with no change in drug combination for at least 3 months at time of enrollment
Plasma viral load <200 copies / ml for at least 6 months prior to enrollment in the study
CD4 T cell count more than 350/ul
Willingness to use a method of contraception during the study period
Willingness to have blood drawn
If female, willingness to undergo pregnancy testing on a monthly basis and are not breastfeeding
Ability to understand and willingness to sign the informed consent
hs-CRP levels above the upper limit of normal (>3mg/L)

Exclusion criteria

Concomitant use of fibric acid derivatives or other lipid lowering agents including patients on statins and Ezetimibe
Use of any anti-inflammatory drugs (OTC or prescription) on a daily basis
Pregnancy or breast feeding
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
Allergy or hypersensitivity to statins or any of its components
History of myositis or rhabdomyolysis with use of any statins
Patients who are on concurrent immunomodulatory agents, including systemic corticosteroids will be ineligible for 3 months after completion of therapy with the immunomodulating agents
History of inflammatory muscle disease such as poly or dermatomyositis
Serious intercurrent illness requiring systemic treatment and/or hospitalization within 30 days of entry
Evidence of active opportunistic infections requiring treatment or neoplasms that require chemotherapy during the study period
Creatine phosphokinase elevations (CPK) greater than 3 times the upper limit of normal
Known active liver disease or AST/ALT greater than 2x the upper limit of normal
Renal insufficiency, indicated by serum creatinine 2 mg/dl
Absolute neutrophil count (ANC) 1000/mm3, hemoglobin < 10.0 g/dL for males and <9 g/dL for females, platelet count 100,000/mm