Clinical trial NCT00672932: Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients
Official title: Pilot Study of Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: raltegravir
central nervous system (CNS)
HIV-1
AIDS
cerebrospinal fluid (CSF)
immunoactivation
antiretroviral therapy
suppression
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: Merck Sharp & Dohme LLC
First posted: 2008-05-06
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in CSF Concentrations of Neopterin After 12 Weeks
timeFrame: three months (Rollover subjects were assessed for a second baseline after the initial 12 week period)
Secondary outcomes:
measure: Change From Baseline in CD8+ T Cell Co-expression of CD38 and HLA-DR
timeFrame: three months (Rollover subjects were assessed for a second baseline after the initial 12 week period)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Ucsf Ccrc, Sfgh
state: California
Study officials:
affiliation: University of California, San Francisco
name: Richard Price, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.