Modulation of Monocyte Activation by Atorvastatin in HIV Infection
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.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Study to Evaluate Effects of Atorvastatin on Monocyte Activation in HAART-treated HIV Infected Individuals|
- Effect of statins on peripheral blood monocytes [ Time Frame: Subjects enrolled in the study following the screening visit will be assessed for the primary outcome measures at T=0 (drug intervention begins); T=2wks; T=6wks; T=12wks (intervention ends); T=16wks (study ends) ] [ Designated as safety issue: No ]
Primary outcome measures include:
- Surface marker analyses of monocyte phenotype
- Plasma levels of soluble inflammatory mediators
- Effect of statins on T cell markers [ Time Frame: Subjects enrolled in the study following the screening visit will be assessed for the secondary outcome measures at T=0 (drug intervention begins); T=2wks; T=6wks; T=12wks (intervention ends); T=16wks (study ends) ] [ Designated as safety issue: No ]
Secondary outcome measures include:
- T cell surface markers
- expanded plasma cytokine profile
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
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.
Other Name: Lipitor
Please refer to this study by its ClinicalTrials.gov identifier: NCT01263938
|United States, Pennsylvania|
|University of Pennsylvania School of Medicine|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Ronald G Collman, MD||University of Pennsylvania|