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

• Status: Completed
• Trial end date: 2011-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Collaborators: Merck Sharp & Dohme Corp.; National Institute of Mental Health (NIMH)
• Treatments: Raltegravir Potassium

Criteria

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.