HIV-1 Specific Immune Responses in Thai Individuals With HIV Dementia
A total of 60 participants will be enrolled. They will be in 3 groups
1. ARV-naÃ¯ve, HIV-positive â‰¥ 20 year of age with HAD (n=20) who intend to start ARV
2. ARV-naÃ¯ve, HIV-positive â‰¥ 20 year of age without HAD (n=20), who intend to start ARV
3. HIV-negative â‰¥ 20 year of age (n=20). 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: 20 HAD individuals, 20 CD4-, education-, gender-, and age-matched non-HAD individuals and 20 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.
Observational Model: Cohort, Time Perspective: Prospective
South East Asia Research Collaboration with Hawaii
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00777426
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of TOGAVIRIDAE INFECTIONS; HERPESVIRIDAE INFECTIONS; ADENOVIRIDAE INFECTIONS; FLAVIVIRIDAE INFECTIONS; BUNYAVIRIDAE INFECTIONS; PICORNAVIRIDAE INFECTIONS; PARAMYXOVIRIDAE INFECTIONS; ORTHOMYXOVIRIDAE INFECTIONS; RETROVIRIDAE INFECTIONS; and ARENAVIRIDAE INFECTIONS.
Viral infections of the leptomeninges and subarachnoid space. TOGAVIRIDAE INFECTIONS; FLAVIVIRIDAE INFECTIONS; RUBELLA; BUNYAVIRIDAE INFECTIONS; ORBIVIRUS infections; PICORNAVIRIDAE INFECTIONS; ORTHOMYXOVIRIDAE INFECTIONS; RHABDOVIRIDAE INFECTIONS; ARENAVIRIDAE INFECTIONS; HERPESVIRIDAE INFECTIONS; ADENOVIRIDAE INFECTIONS; JC VIRUS infections; and RETROVIRIDAE INFECTIONS may cause this form of meningitis. Clinical manifestations include fever, headache, neck pain, vomiting, PHOTOPHOBIA, and signs of meningeal irritation. (From Joynt, Clinical Neurology, 1996, Ch26, pp1-3)
Infections with viruses of the family PARAMYXOVIRIDAE. This includes MORBILLIVIRUS INFECTIONS; RESPIROVIRUS INFECTIONS; PNEUMOVIRUS INFECTIONS; HENIPAVIRUS INFECTIONS; AVULAVIRUS INFECTIONS; and RUBULAVIRUS INFECTIONS.
Central Nervous System Infections
Pathogenic infections of the brain, spinal cord, and meninges. DNA VIRUS INFECTIONS; RNA VIRUS INFECTIONS; BACTERIAL INFECTIONS; MYCOPLASMA INFECTIONS; SPIROCHAETALES INFECTIONS; fungal infections; PROTOZOAN INFECTIONS; HELMINTHIASIS; and PRION DISEASES may involve the central nervous system as a primary or secondary process.
Infections with viruses of the order MONONEGAVIRALES. The concept includes FILOVIRIDAE INFECTIONS; PARAMYXOVIRIDAE INFECTIONS; and RHABDOVIRIDAE INFECTIONS.
The primary objective is to assess the safety of telithromycin (HMR 3647) (20% fine granules) 1g filling sachet in children with infections (Respiratory tract infections, Dermatological in...
The purpose of this study is to determine the effect of an approved medication for adults for an investigational use in pediatric patients 3 months to 17 years for the treatment of complic...
Adults admitted to intensive care units are at risk for a variety of complications. One of the most frequent complications is the development of new infections. Infections due to a fungus...
The purpose of this multicentre prospective trial is to determine the incidence and risk factors for surgical wound infections. Also the investigators will evaluate consequences of wound i...
To determine the pharmacokinetic profile and to evaluate the safety and tolerability of ascending multiple doses of tigecycline in patients aged 8 to 11 years with selected serious infecti...
Disseminated infections with non-tuberculous mycobacteria (NTM) are a life-threatening AIDS-defining illness. Localized infections include pulmonary and extra-pulmonary disease as well as the immune r...
Epidemiology, risk factors and clinical impact of infections by multiresistant bacteria in cirrhosis are poorly known. METHODS: Prospective evaluation in 2 series of cirrhotic patients admitted with i...
The orthopedic community has begun to witness a worrisome rise in the incidence of periprosthetic joint infections (PJIs) caused by resistant organisms. Besides other challenges associated with treati...
Vascular infections present in a multitude of ways with computed tomography (CT) aiding in the diagnosis of many of the uncommon vascular infections, which are equally dangerous and carry severe life-...
At the beginning of the twentieth century Western Europe and the USA experienced an increasing interest in combating venereal diseases. Although infections in children with venereal diseases had been...