HIV-1 Specific Immune Responses in Thai Individuals With HIV Dementia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Assess the HIV-1 specific CD4+ T helper cell and CD8+ CTL responses in individuals with and without HAD prior to initiation of ARV
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Assess the HIV-1 specific CD4+ T helper cell and CD8+ CTL responses in individuals with and without HAD prior to initiation of ARV
时间窗: May 2013
次要结局
- 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)
- Correlate the impact of ARV on HAD with qualitative and quantitative changes in CD4+ and CD8+ HIV-1 specific responses(May 2013)
研究者
Assoc.Prof.Jintanat Ananworanich, M.D.
Assoc.Prof.Jintanat Ananworanich, M.D.
SEARCH Research Foundation