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NCT Number: NCT01263938

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.

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Key information

Conditions

HIV Dementia AIDS Dementia Complex Blood-Borne Infections Brain Diseases Central Nervous System Diseases Communicable Diseases Dementia Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Inflammation Lentivirus Infections Mental Disorders Nervous System Diseases Neurocognitive Disorders Pathologic Processes Pathological Conditions, Signs and Symptoms RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Urogenital Diseases Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

atorvastatin

Drug

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 names: Lipitor

Primary outcomes

  1. Change in Monocyte Surface Markers Expression (Expressed as Percentage), Following Treatment of Chronic HIV+/ HAART+ Subjects With Atorvastatin (T=12wks Versus T=0wk).

    Time frame: Subjects enrolled in the study following the screening visit were assessed for the primary outcome measures at T=0 (drug intervention begins); T=12wks (intervention ends)

    Effects of Atorvastatin on immune activation associated surface markers (CD16, CD163 and CCR2) of monocytes were assessed in chronic HIV+/HAART+ subjects following 12 weeks of treatment. Whole blood drawn from these subjects were stained with fluorochrome tagged antibodies to the surface markers. Stained whole blood cells were then acquired on a flow cytometer and analyzed using the Flowjo software to determine the percentage of cells (monocytes) expressing the specific marker. This was done before starting and after completing drug treatment to assess the effect of drug.

  2. Change From Baseline in Levels of Plasma Inflammatory Marker MCP-1 of Chronic HIV+/ HAART+ Subjects.

    Time frame: Subjects enrolled in the study following the screening visit were assessed for the primary outcome measures at T=0 (drug intervention begins); T=12wks (intervention ends)

    Monocyte specific inflammatory soluble factor MCP-1 was measured by ELISA in plasma of HIV+/HAART+ subjects at baseline and at 12 weeks following atorvastatin treatment.

  3. Change From Baseline in Levels of Plasma Inflammatory Marker sCD14 of Chronic HIV+/ HAART+ Subjects.

    Time frame: Subjects enrolled in the study following the screening visit were assessed for the primary outcome measures at T=0 (drug intervention begins); T=12wks (intervention ends)

    Monocyte specific inflammatory soluble factor sCD14 was measured by ELISA in plasma of HIV+/HAART+ subjects at baseline and at 12 weeks following atorvastatin treatment.

  4. Change From Baseline in Levels of Plasma Inflammatory Marker sCD163 of Chronic HIV+/ HAART+ Subjects.

    Time frame: Subjects enrolled in the study following the screening visit were assessed for the primary outcome measures at T=0 (drug intervention begins); T=12wks (intervention ends)

    Monocyte specific inflammatory soluble factor sCD163 was measured by ELISA in plasma of HIV+/HAART+ subjects at baseline and at 12 weeks following atorvastatin treatment.

Sponsors and collaborators

Lead sponsor

University of Pennsylvania

Other

Collaborators

  • National Institute of Allergy and Infectious Diseases (NIAID)

Registry information

Official study title

Pilot Study to Evaluate Effects of Atorvastatin on Monocyte Activation in HAART-treated HIV Infected Individuals

Important dates

Study start
2011
Primary completion
2017
Study completion
2017
First posted
Dec 21, 2010
Registry last updated
May 1, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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