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

This study has been completed.
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00672932
First received: April 29, 2008
Last updated: May 29, 2013
Last verified: May 2013

April 29, 2008
May 29, 2013
April 2008
October 2010   (final data collection date for primary outcome measure)
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) ] [ Designated as safety issue: No ]
CSF markers of immuno¬activation and inflammation after 12 weeks compared to baseline.
Changes in blood T cell activation as measured by co-expression of CD38 and HLA-DR on the surface of blood CD4+ T cells [ Time Frame: three months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00672932 on ClinicalTrials.gov Archive Site
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) ] [ Designated as safety issue: No ]
Blood CD8+ T cell activation as indicated by percentage of cells in fresh specimens coexpressing surface CD38 and human leukocyte antigen (HLA)-DR.
Changes in blood neopterin, IP-10, and MCP-1 [ Time Frame: three months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients
Pilot Study of Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients

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.

Not Provided
Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
HIV Infections
Drug: raltegravir
400 mg two times daily for three months
Other Name: Isentress
  • Experimental: raltegravir group
    The raltegravir dosing will be 400mg twice daily by mouth. Subjects will continue all of their regular medications throughout the protocol.
    Intervention: Drug: raltegravir
  • No Intervention: No augmented treatment
    Subjects randomized not to receive augmented treatment will continue in the study with their regular antiretroviral regimen.
Dahl V, Lee E, Peterson J, Spudich SS, Leppla I, Sinclair E, Fuchs D, Palmer S, Price RW. Raltegravir treatment intensification does not alter cerebrospinal fluid HIV-1 infection or immunoactivation in subjects on suppressive therapy. J Infect Dis. 2011 Dec 15;204(12):1936-45. doi: 10.1093/infdis/jir667. Epub 2011 Oct 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
February 2011
October 2010   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00672932
CCRC5004, R01 MH 62701
No
University of California, San Francisco
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
University of California, San Francisco
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP