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.

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.

12 weeks

6 subjects who rolled over to treatment after 12 weeks of no treatment were followed for an additional 12 weeks. 1 subject in the Raltegravir group was not included in other analyses because a pharmacological study showed no drug in either plasma or CSF.

The underlying hypothesis might not have actually been addressed because of the particular makeup of the subject group with minimal CNS infection and immunoactivation that left little room to discern a therapeutic effect.