HIV Levels in Cerebrospinal Fluid and Brain Function in Patients Receiving Anti-HIV Drugs

HIV Infections Clinical Trial

Official title:

Cerebrospinal Fluid Human Immunodeficiency Virus-1 (HIV-1) and Cognitive Function in Individuals Receiving Potent Antiretroviral Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001103
• Other study ID #: ACTG 736
• Secondary ID: AACTG 736
• Status: Completed
• Phase: N/A
• First received: November 2, 1999
• Last updated: July 28, 2008

Study information

• Verified date: May 2006
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to see whether anti-HIV drugs that reduce HIV in the blood also reduce HIV in the cerebrospinal fluid (CSF). CSF is the fluid found around the brain and spinal cord. This study also looks at whether reducing HIV in the CSF can help protect brain function.

HIV can be detected in the brain and CSF early in HIV disease. Anti-HIV drugs probably reduce HIV in the CSF. This may be important because other studies have suggested high CSF HIV levels may lead to some loss of brain function.

Description:

HIV-1 RNA emerges in CSF early in the course of HIV disease. Studies have shown that high levels of HIV-1 RNA in CSF correlate with increased severity of dementia and worsened performance on neuropsychological tests. While combination antiretroviral treatments are potent suppressors of HIV-1 replication in plasma, the extent to which these treatments suppress viral replication in CSF is unknown. A few studies suggest that antiretroviral treatments can reduce HIV-1 RNA in CSF. However, since CSF is isolated from peripheral immune responses to HIV and antiretroviral treatment may not readily penetrate the compartment, researchers hypothesize the remaining virus will overcome the antiretroviral treatment to achieve high levels of viral replication again. This virologic failure is likely accompanied by decreased cognitive function. It is therefore critical to determine the ability of antiretroviral treatments to control HIV-1 replication in the CSF and the durability of that viral suppression.

Patients enrolling in one of several AACTG-sponsored potent antiretroviral therapy trials (a "parent" trial) may enter this study. [AS PER AMENDMENT 06/06/00: Patients already enrolled in an AACTG-sponsored study who are changing treatment due to virologic failure may also enter this study.] [AS PER AMENDMENT 11/15/01: Patients starting a new potent antiretroviral regimen as part of their clinical care, enrolling in a potent antiretroviral treatment trial, or changing potent antiretroviral therapy in clinical care or in an ongoing antiretroviral treatment trial because of virologic failure may enter this study.] Patients receive no treatment but undergo various procedures aimed at characterizing the effects of antiretroviral therapies on CSF viral load and cognitive function. Procedures include: 1) venipuncture to measure plasma HIV-1 RNA and DNA levels, CD4+ T cell count, and cytokine and immune activation markers associated with HIV-1 neurological disorders; 2) neuropsychological examinations to measure cognitive function; and 3) lumbar punctures to obtain CSF samples, which are used to determine the pharmacokinetics of antiretroviral agents in CSF and to determine levels of blood cells, cytokine and immune activation markers, and HIV-1 RNA and DNA. An entry visit must occur before initiating potent antiretroviral therapy in the parent trial [AS PER AMENDMENT 06/06/00: or before changing the antiretroviral regimen due to virologic failure in an ongoing trial]. [AS PER AMENDMENT 11/15/01: Patients are registered before initiating a new potent antiretroviral regimen.] Subsequent visits occur within 21 days prior to each lumbar puncture and at Weeks 24 and 52. If evaluations, procedures, or assays for a given patient's parent trial [AS PER AMENDMENT 11/15/01: for any coenrollment AACTG study] occur at the times specified in this study, they are not duplicated for this study. Other visits may occur when a patient changes antiretroviral treatment or discontinues a parent trial [AS PER AMENDMENT 11/15/01: discontinues a potent antiretroviral therapy].

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria

• Are HIV-positive.

• Have levels of CD4 cells (immune cells that fight infection) less than 200 cells/mm3 and viral loads (level of HIV in the blood) greater than 2,000 copies/ml or viral loads greater than 50,000 copies/ml and any CD4 cell levels.

• Are either: 1) starting a new potent antiretroviral therapy for HIV; 2) enrolling in a potent antiretroviral trial; or 3) currently participating in an ongoing antiretroviral trial or in clinical care and will be changing treatment due to treatment failure. The entry visit for ACTG 736 must occur before starting the treatment or before changing to the new treatment. (This study has been changed to include patients who have changed treatment due to treatment failure and those who are starting a new anti-HIV regimen.)

Exclusion Criteria

• Have an infection or cancer in the brain or certain diseases of the brain or nervous system.

• Have a serious psychiatric illness (such as schizophrenia or severe depression).

• Have completed treatment for a significant infection within 4 weeks of beginning the study (but certain drugs that fight infection are allowed on this study).

• Are taking drugs to prevent or dissolve blood clots.

• Abuse drugs or alcohol.

Study Design

N/A

Related Conditions & MeSH terms

• Cognition Disorders
• Cognitive Disorders
• HIV Infections

Locations

Country	Name	City	State
Puerto Rico	Univ of Puerto Rico	San Juan
United States	Johns Hopkins Hosp	Baltimore	Maryland
United States	Northwestern Univ Med School	Chicago	Illinois
United States	Univ of Cincinnati	Cincinnati	Ohio
United States	Case Western Reserve Univ	Cleveland	Ohio
United States	MetroHealth Med Ctr	Cleveland	Ohio
United States	Ohio State Univ Hosp Clinic	Columbus	Ohio
United States	Univ of Texas, Southwestern Med Ctr of Dallas	Dallas	Texas
United States	Univ of Colorado Health Sciences Ctr	Denver	Colorado
United States	Univ of Hawaii	HonolulU	Hawaii
United States	Willow Clinic	Menlo Park	California
United States	Comprehensive Care Clinic	Nashville	Tennessee
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Beth Israel Med Ctr	New York	New York
United States	Columbia Presbyterian Med Ctr	New York	New York
United States	Mount Sinai Med Ctr	New York	New York
United States	Univ of Pennsylvania at Philadelphia	Philadelphia	Pennsylvania
United States	Univ of Pittsburgh	Pittsburgh	Pennsylvania
United States	Miriam Hosp / Brown Univ	Providence	Rhode Island
United States	Univ of Rochester Medical Center	Rochester	New York
United States	Univ of California / San Diego Treatment Ctr	San Diego	California
United States	San Francisco Gen Hosp	San Francisco	California
United States	Univ of Washington	Seattle	Washington
United States	San Mateo AIDS Program / Stanford Univ	Stanford	California
United States	Stanford Univ Med Ctr	Stanford	California
United States	Julio Arroyo	West Columbia	South Carolina

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	National Institute of Neurological Disorders and Stroke (NINDS), Neurologic AIDS Research Consortium (NARC)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

External Links

•   Haga clic aquí para ver información sobre este ensayo clínico en español.