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

University of California San Francisco (UCSF)

Status: Completed

Conditions: HIV Infections

Treatments: Drug: raltegravir

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00672932

CCRC5004

R01MH062701 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

18 participants in 2 patient groups

raltegravir group

Experimental group

Description:

The raltegravir dosing will be 400mg twice daily by mouth. Subjects will continue all of their regular medications throughout the protocol.

Treatment:

Drug: raltegravir

No augmented treatment

No Intervention group

Description:

Subjects randomized not to receive augmented treatment will continue in the study with their regular antiretroviral regimen.