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

Completed
Conditions
Cognitive Disorders
HIV Infections
Registration Number
NCT00001103
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief 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.

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 \[AS PER AMENDMENT 11/15/01: discontinues a potent antiretroviral therapy\].

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
100
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (26)

Univ of Colorado Health Sciences Ctr

🇺🇸

Denver, Colorado, United States

Ohio State Univ Hosp Clinic

🇺🇸

Columbus, Ohio, United States

Univ of California / San Diego Treatment Ctr

🇺🇸

San Diego, California, United States

Univ of Cincinnati

🇺🇸

Cincinnati, Ohio, United States

Univ of Pennsylvania at Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

San Francisco Gen Hosp

🇺🇸

San Francisco, California, United States

Univ of Rochester Medical Center

🇺🇸

Rochester, New York, United States

Beth Israel Med Ctr

🇺🇸

New York, New York, United States

Northwestern Univ Med School

🇺🇸

Chicago, Illinois, United States

Case Western Reserve Univ

🇺🇸

Cleveland, Ohio, United States

Columbia Presbyterian Med Ctr

🇺🇸

New York, New York, United States

Stanford Univ Med Ctr

🇺🇸

Stanford, California, United States

Univ of Hawaii

🇺🇸

HonolulU, Hawaii, United States

MetroHealth Med Ctr

🇺🇸

Cleveland, Ohio, United States

Willow Clinic

🇺🇸

Menlo Park, California, United States

Univ of Pittsburgh

🇺🇸

Pittsburgh, Pennsylvania, United States

Julio Arroyo

🇺🇸

West Columbia, South Carolina, United States

Comprehensive Care Clinic

🇺🇸

Nashville, Tennessee, United States

Bellevue Hosp / New York Univ Med Ctr

🇺🇸

New York, New York, United States

Mount Sinai Med Ctr

🇺🇸

New York, New York, United States

San Mateo AIDS Program / Stanford Univ

🇺🇸

Stanford, California, United States

Miriam Hosp / Brown Univ

🇺🇸

Providence, Rhode Island, United States

Univ of Washington

🇺🇸

Seattle, Washington, United States

Univ of Texas, Southwestern Med Ctr of Dallas

🇺🇸

Dallas, Texas, United States

Univ of Puerto Rico

🇵🇷

San Juan, Puerto Rico

Johns Hopkins Hosp

🇺🇸

Baltimore, Maryland, United States

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