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

This study has been completed.
National Institute of Mental Health (NIMH)
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of California, San Francisco Identifier:
First received: April 29, 2008
Last updated: May 29, 2013
Last verified: May 2013
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.

Condition Intervention
HIV Infections
Drug: raltegravir

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Pilot Study of Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients

Resource links provided by NLM:

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Change in CSF Concentrations of Neopterin After 12 Weeks [ Time Frame: three months (Rollover subjects were assessed for a second baseline after the initial 12 week period) ]
    CSF markers of immuno¬activation and inflammation after 12 weeks compared to baseline.

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

Enrollment: 18
Study Start Date: April 2008
Study Completion Date: February 2011
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: raltegravir group
The raltegravir dosing will be 400mg twice daily by mouth. Subjects will continue all of their regular medications throughout the protocol.
Drug: raltegravir
400 mg two times daily for three months
Other Name: Isentress
No Intervention: No augmented treatment
Subjects randomized not to receive augmented treatment will continue in the study with their regular antiretroviral regimen.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
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Please refer to this study by its identifier: NCT00672932

United States, California
Ucsf Ccrc, Sfgh
San Francisco, California, United States, 94110
Sponsors and Collaborators
University of California, San Francisco
National Institute of Mental Health (NIMH)
Merck Sharp & Dohme Corp.
Principal Investigator: Richard Price, MD University of California, San Francisco
  More Information

Responsible Party: University of California, San Francisco Identifier: NCT00672932     History of Changes
Other Study ID Numbers: CCRC5004
R01MH062701 ( US NIH Grant/Contract Award Number )
Study First Received: April 29, 2008
Results First Received: June 18, 2012
Last Updated: May 29, 2013

Keywords provided by University of California, San Francisco:
central nervous system (CNS)
cerebrospinal fluid (CSF)
antiretroviral therapy

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Raltegravir Potassium
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on May 24, 2017