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

July 28, 2008 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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

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.

Study Overview

Status

Completed

Conditions

Detailed 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].

Study Type

Observational

Enrollment

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 009365067
        • Univ of Puerto Rico
  • United States
    • California
      • Menlo Park, California, United States, 94025
        • Willow Clinic
      • San Diego, California, United States, 921036325
        • Univ of California / San Diego Treatment Ctr
      • San Francisco, California, United States, 941102859
        • San Francisco Gen Hosp
      • Stanford, California, United States, 943055107
        • San Mateo AIDS Program / Stanford Univ
      • Stanford, California, United States, 943055107
        • Stanford Univ Med Ctr
    • Colorado
      • Denver, Colorado, United States, 80262
        • Univ of Colorado Health Sciences Ctr
    • Hawaii
      • HonolulU, Hawaii, United States, 96816-2396
        • Univ of Hawaii
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Univ Med School
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Hosp
    • New York
      • New York, New York, United States, 10003
        • Beth Israel Med Ctr
      • New York, New York, United States, 10016
        • Bellevue Hosp / New York Univ Med Ctr
      • New York, New York, United States, 10029
        • Mount Sinai Med Ctr
      • New York, New York, United States, 10032
        • Columbia Presbyterian Med Ctr
      • Rochester, New York, United States, 14642
        • Univ of Rochester Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 452670405
        • Univ of Cincinnati
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve Univ
      • Cleveland, Ohio, United States, 441091998
        • MetroHealth Med Ctr
      • Columbus, Ohio, United States, 432101228
        • Ohio State Univ Hosp Clinic
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Univ of Pennsylvania at Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15213
        • Univ of Pittsburgh
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • Miriam Hosp / Brown Univ
    • South Carolina
      • West Columbia, South Carolina, United States, 29169
        • Julio Arroyo
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Comprehensive Care Clinic
    • Texas
      • Dallas, Texas, United States, 75390
        • Univ of Texas, Southwestern Med Ctr of Dallas
    • Washington
      • Seattle, Washington, United States, 98104
        • Univ of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)
Neurologic AIDS Research Consortium (NARC)

Investigators

  • Study Chair: Christina Marra, MD, University of Washington
  • Study Chair: Kevin Robertson, PhD, University of North Carolina, Chapel Hill

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Estimate)

July 29, 2008

Last Update Submitted That Met QC Criteria

July 28, 2008

Last Verified

May 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 736
  • AACTG 736

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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