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

HIV Infections Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00777426
• Other study ID #: SEARCH 007
• Status: Completed
• Phase: N/A
• First received: October 21, 2008
• Last updated: September 25, 2014
• Start date: September 2008
• Est. completion date: October 2013

Study information

• Verified date: September 2014
• Source: South East Asia Research Collaboration with Hawaii
• Contact: n/a
• Is FDA regulated: No
• Health authority: Thailand: Ethical Committee
• Study type: Observational

Clinical Trial Summary

A total of 60 participants will be enrolled. They will be in 3 groups

1. ARV-naïve, HIV-positive ≥ 20 year of age with HAD (n=25) who intend to start ARV

2. ARV-naïve, HIV-positive ≥ 20 year of age without HAD (n=25), who intend to start ARV

3. 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: October 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

Group Thai HAD individuals

• 20 years of age

• not currently receiving nor have ever received antiretroviral medications

• not explained by opportunistic infections or causes other than HIV on the basis of clinical assessment and neuropsychological testing and eligible for inclusion.

Group Thai Non-HAD individuals

• will be matched with a seropositive Thai patient with similar age (same decade), education (less than high school degree, high school degree +/- some college, college degree +), gender, and CD4 group

• HIV positive

• not currently receiving nor have ever received antiretroviral medications.

Group Thai Non-HAD individuals will be matched with a Thai seronegative patient by age (same decade), and education (less than high school degree, high school degree +/- some college, college degree+), and gender.

Exclusion Criteria:

• Head injury with loss of consciousness greater than 1 hour

• Current or past illicit drug use (less then 5 years) or positive drug screen for amphetamine, methamphetamines, cocaine, marijuana, or narcotics at either screening or entry.

• Inability to provide informed consent or lack of designated surrogate who can provide consent

• The following laboratory values:

• PT/PTT > the upper limit of normal (ULN) or INR > 1.1

• Hemoglobin < 9.0 mg/dL

• ALT > 5x ULN

• serum creatinine > 2x ULN or creatinine clearance < 30 cc per min by Cockroft-Gault formula

• Acute illness within 30 days prior to entry, persistent and active AIDS- defining opportunistic infection or autoimmune disease. Stable treated opportunistic infections on maintenance therapy, minor infections such as oral thrush and Kaposi's Sarcoma limited to the skin will be allowed.

• Current or recent fevers or meningeal signs suggestive of CNS opportunistic infection.*

• History of pre-existing neurologic disease to include stroke, multiple sclerosis

• History of psychiatric illness including schizophrenia, bipolar disorder, anxiety disorder, panic attacks, or post traumatic stress disorder. Patients with active major depression will be excluded as well - patients with past depression that is controlled and patients with or minor depressive symptoms will be allowed to enroll.

• Known learning disability including dyslexia.

• Positive Hepatitis C serology (Hepatitic C Ab)

• Confusion or other signs and symptoms of metabolic encephalopathy or delirium

• Mass consistent with opportunistic infection or tumor on CT or MRI of the head, or focal neurological deficit on examination consistent with possible brain lesion.*

• Other conditions that could explain neurocognitive decline in the opinion of the investigator such as hypothyroidism, vitamin B12 deficiency or neurosyphilis.

• Pregnancy.

• Not willing to take an MRI.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• HIV Infections

Locations

Country	Name	City	State
Thailand	SEARCH Thailand	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
South East Asia Research Collaboration with Hawaii

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess the HIV-1 specific CD4+ T helper cell and CD8+ CTL responses in individuals with and without HAD prior to initiation of ARV		May 2013	No
Secondary	Measure M/M dysregulation/activation and correlate this with HIV-1 specific CD4+ and CD8+ T cell responses prior to initiation of ARV		May 2013	No
Secondary	Correlate the impact of ARV on HAD with qualitative and quantitative changes in CD4+ and CD8+ HIV-1 specific responses		May 2013	No

External Links

•   South East Asia Research Collaboration with Hawaii (SEARCH)