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

University of California, San Francisco18 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Masking

NONE

Enrollment

Conditions

HIV Infections

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Change in CSF Concentrations of Neopterin After 12 Weeks

CSF markers of immuno¬activation and inflammation after 12 weeks compared to baseline.

Time frame: three months (Rollover subjects were assessed for a second baseline after the initial 12 week period)

Secondary Outcomes

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.