hiv-1 specific immune responses in thai individuals with hiv dementia

Conditions: HIV Infections

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.

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.

Eligibility criteria:
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.

Keywords: hiv positive with had