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