Clinical trial NCT00001103: HIV Levels in Cerebrospinal Fluid and Brain Function in Patients Receiving Anti-HIV Drugs
Official title: Cerebrospinal Fluid Human Immunodeficiency Virus-1 (HIV-1) and Cognitive Function in Individuals Receiving Potent Antiretroviral Therapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cognitive Disorders
HIV Infections
Keywords: Neuropsychological Tests
HIV-1
RNA, Viral
Anti-HIV Agents
Viral Load
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Neurologic AIDS Research Consortium (NARC)
First posted: 2001-08-31
Enrollment: 100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no

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

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Menlo Park
country: United States
facility: Willow Clinic
state: California
city: San Diego
country: United States
facility: Univ of California / San Diego Treatment Ctr
state: California
city: San Francisco
country: United States
facility: San Francisco Gen Hosp
state: California
city: Stanford
country: United States
facility: San Mateo AIDS Program / Stanford Univ
state: California
city: Stanford
country: United States
facility: Stanford Univ Med Ctr
state: California
city: Denver
country: United States
facility: Univ of Colorado Health Sciences Ctr
state: Colorado
city: HonolulU
country: United States
facility: Univ of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Univ Med School
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Hosp
state: Maryland
city: New York
country: United States
facility: Beth Israel Med Ctr
state: New York
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: Mount Sinai Med Ctr
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Med Ctr
state: New York
city: Rochester
country: United States
facility: Univ of Rochester Medical Center
state: New York
city: Cincinnati
country: United States
facility: Univ of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve Univ
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Med Ctr
state: Ohio
city: Columbus
country: United States
facility: Ohio State Univ Hosp Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Univ of Pennsylvania at Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Univ of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Miriam Hosp / Brown Univ
state: Rhode Island
city: West Columbia
country: United States
facility: Julio Arroyo
state: South Carolina
city: Nashville
country: United States
facility: Comprehensive Care Clinic
state: Tennessee
city: Dallas
country: United States
facility: Univ of Texas, Southwestern Med Ctr of Dallas
state: Texas
city: Seattle
country: United States
facility: Univ of Washington
state: Washington
city: San Juan
country: Puerto Rico
facility: Univ of Puerto Rico
Study officials:
affiliation: University of Washington
name: Christina Marra, MD
role: STUDY_CHAIR
affiliation: University of North Carolina, Chapel Hill
name: Kevin Robertson, PhD
role: STUDY_CHAIR
References: