Phase 4
Completed N=5
Modulation of Monocyte Activation by Atorvastatin in HIV Infection
HIV Dementia
Source: ClinicalTrials.gov NCT01263938 ↗
Enrolled (actual)
5
Serious AEs
0.0%
Results posted
Apr 2019
Primary outcomePrimary: Change in Monocyte Surface Markers Expression (Expressed as Percentage), Following Treatment of Chronic HIV+/ HAART+ Subjects With Atorvastatin (T=12wks Versus T=0wk). — 1.5; -4.4; 0.5 Change T=0 to T=12 (percentage change) — p=0.625
◆ Published Evidence
No publication linked
No peer-reviewed publication reporting this trial's results has been linked yet. This can indicate results are unpublished — a known publication-bias signal. We re-check periodically.
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Monocyte Surface Markers Expression (Expressed as Percentage), Following Treatment of Chronic HIV+/ HAART+ Subjects With Atorvastatin (T=12wks Versus T=0wk). |
1.5; -4.4; 0.5 | 0.625 |
| PRIMARY Change From Baseline in Levels of Plasma Inflammatory Marker MCP-1 of Chronic HIV+/ HAART+ Subjects. |
10 | >0.999 |
| PRIMARY Change From Baseline in Levels of Plasma Inflammatory Marker sCD14 of Chronic HIV+/ HAART+ Subjects. |
-0.22 | 0.813 |
| PRIMARY Change From Baseline in Levels of Plasma Inflammatory Marker sCD163 of Chronic HIV+/ HAART+ Subjects. |
-18 | 0.625 |
Eligibility Criteria
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 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
Data sourced from ClinicalTrials.gov (NCT01263938). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.