Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients

Study Overview
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Brief Summary
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This pilot study focuses on the persistence of central nervous system (CNS) immune activation that has been observed in the presence of 'effective' combination antiretroviral therapy (cART). Attention to this issue is based on the fear that chronic CNS immunoactivation can cause indolent brain injury that will eventually compromise brain function as patients survive for years on treatment. A leading hypothesis explaining this continued immunoactivation is that viral replication continues within the brain at a level too low for detection in cerebrospinal fluid (CSF), yet sufficient to stimulate local immunoactivation. Based on this hypothesis, we propose to use augmented treatment with raltegravir to test whether additional suppression of this hypothesized CNS HIV-1 replication will reduce continued CNS immunoactivation.

Official Title
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Pilot Study of Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: raltegravir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capacity to provide informed consent. Documented HIV-1 infection. History of continuous cART treatment (with at least three drugs) for at least 2 years. Documentation of 'undetectable' plasma HIV-1 RNA for at least 1 year. HIV-1 RNA <50 copies/mL in plasma and CSF at screening visit. Exclusion Criteria: Contraindication to LP (suspicion of CNS mass lesion, bleeding diathesis, etc.). Prior experience with raltegravir or contraindication to raltegravir treatment, including medication interactions that might compromise ongoing antiretroviral therapy or treatment of other conditions. Active opportunistic infections or neurological diseases. Other conditions or treatments likely to interfere with treatment or evaluation. Hemoglobin < 10 Gm/dL. Pregnant or anticipating pregnancy during study. Active substance abuse. Subjects taking rifampin, phenytoin, Phenobarbital or other drugs that accelerate raltegravir metabolism and might decrease its tissue concentrations.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: raltegravir group<br>The raltegravir dosing will be 400mg twice daily by mouth. Subjects will continue all of their regular medications throughout the protocol. | Drug: raltegravir<br>* 400 mg two times daily for three months<br>* Other names: Isentress;|
| No Intervention: No augmented treatment<br>Subjects randomized not to receive augmented treatment will continue in the study with their regular antiretroviral regimen. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CSF Concentrations of Neopterin After 12 Weeks | CSF markers of immuno¬activation and inflammation after 12 weeks compared to baseline. | three months (Rollover subjects were assessed for a second baseline after the initial 12 week period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in CD8+ T Cell Co-expression of CD38 and HLA-DR | Blood CD8+ T cell activation as indicated by percentage of cells in fresh specimens coexpressing surface CD38 and human leukocyte antigen (HLA)-DR. | three months (Rollover subjects were assessed for a second baseline after the initial 12 week period) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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raltegravir, central nervous system (CNS), HIV-1, AIDS, cerebrospinal fluid (CSF), immunoactivation, antiretroviral therapy, suppression