CNS (Central Nervous System) Viral Dynamics and Cellular Immunity During AIDS
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|ClinicalTrials.gov Identifier: NCT00583167|
Recruitment Status : Completed
First Posted : December 31, 2007
Last Update Posted : May 28, 2014
Understanding whether or not viral replication occurs in the brain during chronic untreated HIV-1 infection is of undeniable importance, and has implications for treatment and research priorities. Evidence suggests that viral replication in the CNS occurs at the extremes of HIV-1 disease. Brain involvement has been reported during acute infection, and there is convincing evidence of CNS viral replication during HIV-associated dementia (HAD) and advanced AIDS. Some human and primate data suggest that viral RNA and proteins may be absent from brains of some individuals with chronic untreated HIV-1 infection despite abundant proviral DNA. However, the extent of viral replication in the brain is not known for most of the 42 million people worldwide living with untreated HIV-1 infection.
Why is viral replication in the brain such a pivotal issue? Microglial cells and macrophages are primary targets for intrathecal HIV-1 replication, and this can promote neuronal injury through direct effects of gp120 and tat, and indirect induction of toxic mediators. Low-grade injury over years or decades would likely be deleterious, particularly as the population ages. Because treatment guidelines allow systemic HIV-1 replication to continue until CD4+ T cell counts decline considerably, antiretroviral therapy (ART) is not recommended for many persons living with HIV. Demonstrating replication in the brain during chronic HIV-1 infection may affect treatment strategies and encourage investigation.
Identifying factors that modulate intrathecal viral replication is equally important. Anti-HIV-1 cytotoxic T lymphocytes (CTL) partially control systemic viral replication and delay disease progression. Although available data has been provocative, the role of anti-HIV CTL in the CNS has received little attention. To fill this gap we will examine relationships between intrathecal viral replication, CTL responses, and glial activation/proliferation during HIV-1 infection. These studies will be relevant not only to AIDS but to other inflammatory diseases of the CNS as well.
|Condition or disease|
|Study Type :||Observational|
|Actual Enrollment :||4 participants|
|Official Title:||CNS Viral Dynamics and Cellular Immunity During AIDS|
|Study Start Date :||March 2006|
|Actual Primary Completion Date :||June 2009|
|Actual Study Completion Date :||July 2010|
HIV-infected subjects who are at least 18 years of age, with no ART in the previous 3 months, and with plasma HIV-1 RNA >20,000 copies/mL. CD4+ T cell count >200 cells/mm3. Group A1 will undergo continuous CSF ( cerebrospinal fluid) sampling via intrathecal catheter.
HIV-infected subjects who are at least 18 years of age, with no ART in the previous 3 months, and with plasma HIV-1 RNA >20,000 copies/mL. CD4+ T cell count <200 cells/mm3. Group A2 will undergo continuous CSF sampling via intrathecal catheter.
HIV-infected subjects who are at least 18 years of age, with no ART in the previous 3 months, and with plasma HIV-1 RNA >20,000 copies/mL. Group B will not undergo continuous CSF sampling, but will undergo sparse CSF sampling by lumbar punctures.
- To characterize intrathecal viral replication during chronic untreated HIV-1 infection, and to assess how intrathecal viral replication relates to stage of HIV-1 disease. [ Time Frame: end of study ]
- To measure intrathecal and systemic cellular immune responses against HIV-1 and to assess how these responses relate to intrathecal viral replication. [ Time Frame: end of study ]
- To correlate intrathecal viral replication and anti-HIV CTL responses with the degree of glial activation/proliferation and neuronal dropout in the brain. [ Time Frame: end of study ]
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00583167
|United States, Tennessee|
|Vanderbilt AIDS Clinical Trials Center|
|Nashville, Tennessee, United States, 37232-2582|
|Principal Investigator:||David W. Haas, MD||Vanderbilt University|