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

NCT00672932 | Completed Results

• 2 other identifiers: CCRC5004R01MH062701
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infections

Keywords

raltegravir; central nervous system (CNS); HIV-1; AIDS; cerebrospinal fluid (CSF); immunoactivation; antiretroviral therapy; suppression

Outcome Measures

Primary Outcomes (1)

• Change in CSF Concentrations of Neopterin After 12 Weeks

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

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

Secondary Outcomes (1)

• Change From Baseline in CD8+ T Cell Co-expression of CD38 and HLA-DR

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

Study Arms (2)

raltegravir group

EXPERIMENTAL

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

Drug: raltegravir

No augmented treatment

NO INTERVENTION

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

Interventions

raltegravir DRUG

400 mg two times daily for three months

Also known as: Isentress

raltegravir group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institute of Mental Health (NIMH): collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Ucsf Ccrc, Sfgh

San Francisco, California, 94110, United States

Location

Related Publications (1)

• 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.

  PMID: 22021620 RESULT

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Raltegravir Potassium

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

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.

Results Point of Contact

• Title: Richard W. Price, M.D.
• Organization: UCSF

rwprice@sfgh.ucsf.edu

415-206-4487

Study Officials

• Richard Price, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2008
• First Posted: May 6, 2008
• Study Start: April 1, 2008
• Primary Completion: October 1, 2010
• Study Completion: February 1, 2011
• Last Updated: July 5, 2013
• Results First Posted: July 5, 2013

Record last verified: 2013-05

Locations

US (1)