HIV-1 Specific Immune Responses in Thai Individuals With HIV Dementia
|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
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|