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Sponsors and Collaborators: |
Vanderbilt University National Institutes of Health (NIH) |
Information provided by: | Vanderbilt University |
ClinicalTrials.gov Identifier: | NCT00583167 |
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 |
HIV Infections |
MedlinePlus related topics: | AIDS |
Study Type: | Observational |
Study Design: | Cohort, Prospective |
Official Title: | CNS Viral Dynamics and Cellular Immunity During AIDS |
whole blood, plasma, CSF
Estimated Enrollment: | 50 |
Study Start Date: | March 2006 |
Estimated Study Completion Date: | December 2010 |
Estimated Primary Completion Date: | March 2010 (Final data collection date for primary outcome measure) |
Groups/Cohorts |
A1
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 sampling via intrathecal catheter.
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A2
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.
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B
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.
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Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Sampling Method: | Non-Probability Sample |
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. Individuals with past ART experience must have the ability to construct an ART regimen predicted to completely suppress plasma HIV-1 RNA, based on results of viral susceptibility testing that is done as a routine part of clinical practice.
Inclusion Criteria:
Exclusion Criteria:
Contact: Deborah Sutherland, RN, BSN | 615-467-0154 ext 109 | deborah.sutherland@vanderbilt.edu |
Contact: Becky Basham | 615-467-0154 ext 117 | rebecca.j.basham@vanderbilt.edu |
United States, Tennessee | |||||
Vanderbilt AIDS Clinical Trials Center | Recruiting | ||||
Nashville, Tennessee, United States, 37203 |
Vanderbilt University |
National Institutes of Health (NIH) |
Principal Investigator: | David W. Haas, MD | Vanderbilt University |
Responsible Party: | Vanderbilt University ( David W. Haas, MD ) |
Study ID Numbers: | 050001, R01 MH071205 |
First Received: | December 26, 2007 |
Last Updated: | August 4, 2008 |
ClinicalTrials.gov Identifier: | NCT00583167 |
Health Authority: | United States: Institutional Review Board; United States: Federal Government |
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