HIV-1 Specific Immune Responses in Thai Individuals With HIV Dementia
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|ClinicalTrials.gov Identifier: NCT00777426|
Recruitment Status : Completed
First Posted : October 22, 2008
Last Update Posted : September 26, 2014
A total of 60 participants will be enrolled. They will be in 3 groups
- ARV-naïve, HIV-positive ≥ 20 year of age with HAD (n=25) who intend to start ARV
- ARV-naïve, HIV-positive ≥ 20 year of age without HAD (n=25), who intend to start ARV
- HIV-negative ≥ 20 year of age (n=10). The protocol team will work with the primary care physician to ensure that the subjects receive standard HIV and ARV care; however, initiation of ARV is not a requirement of the study and ARV will not be provided by the study.
Participant accrual will include 10-15 participants per year. HIV-positive subjects will be tentatively enrolled in HAD vs. non-HAD groups by the enrolling neurologist and subsequently confirmed to that group by a consensus conference held every 6 months by the study neurologists. In cases of disagreement, cases will be re-assigned to the consensus conference determination and recruitment will continue. An external validation consensus conference will be conducted as well every 6-12 months to monitor correct assignment of the level of impairment.
|Condition or disease|
This application focuses on the role of cellular immune responses in HIV dementia (HAD) versus non-HAD individuals in a cognitively characterized cohort followed for one year.
Increasing evidence links strong CD4+ T helper function to robust CD8+ CTL responses. HIV-1-infected individuals who are able to maintain strong HIV-1 specific T cell responses have better clinical outcomes and rarely develop neurological signs or symptoms. Monocyte/macrophage (M/M) infiltration into the white matter of the brain is a hallmark of HAD; however, the mechanisms by which M/M are recruited to the brain are not clearly understood. We hypothesize that the loss of specific HIV-1 T cell response results in activation/dysregulation of M/M leading to their accumulation in the brain.
To test this hypothesis will characterize Thai HIV-1-infected individuals as follows: 25 HAD individuals, 25 CD4-, education-, gender-, and age-matched non-HAD individuals and 10 HIV negative controls. We will then: 1) define CD4+ and CD8+ T cell function by evaluating HIV-1 specific responses in HAD vs. non-HAD groups; 2) simultaneously correlate these responses to M/M subpopulation cell number, percentage, and immune function; 3) correlate these responses to HIV-1 proviral load and autologous viral sequences (viral escape sequences and HIV quasispecies); and 4) evaluate the impact of ARV on dementia related to changes in immunological responses. Since little is known of the interaction between CD4+ T helper responses, CTL function, and the level of M/M subpopulation activation in the neuropathogenesis of HAD, this innovative study will elucidate the role of HIV-1 specific immune responses in HAD and provide new insights into HIV-1 neuropathogenesis and its relationship to peripheral immune responses, potentially opening exciting new areas for further investigation.
|Study Type :||Observational|
|Actual Enrollment :||60 participants|
|Study Start Date :||September 2008|
|Actual Primary Completion Date :||June 2013|
|Actual Study Completion Date :||October 2013|
|Thai HAD individuals (25 cases)|
|Thai Non-HAD individuals (25 cases)|
|Thai Non-infected individuals (10 cases)|
- Assess the HIV-1 specific CD4+ T helper cell and CD8+ CTL responses in individuals with and without HAD prior to initiation of ARV [ Time Frame: May 2013 ]
- Measure M/M dysregulation/activation and correlate this with HIV-1 specific CD4+ and CD8+ T cell responses prior to initiation of ARV [ Time Frame: May 2013 ]
- Correlate the impact of ARV on HAD with qualitative and quantitative changes in CD4+ and CD8+ HIV-1 specific responses [ Time Frame: May 2013 ]
Biospecimen Retention: Samples Without 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): NCT00777426
|Bangkok, Thailand, 10330|
|Study Chair:||Jintanat Ananworanich, MD||South East Asia Research Collaboration with Hawaii|