Evaluation of Viral Factors and Immune Parameters to Study HIV-Specific Immunity
Overview
- Phase
- Not Applicable
- Intervention
- Long term nonprogressors
- Conditions
- HIV
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 400
- Locations
- 1
- Primary Endpoint
- Perform genetic studies to characterize immune-related susceptibility/protective genes and compare these between patients groups and within families.
- Status
- Recruiting
- Last Updated
- 5 days ago
Overview
Brief Summary
This study will collect white blood cells and plasma for research on how the immune system controls HIV infection. The immune system of a very small group of people with HIV, called non-progressors, has been able to control HIV for long periods without antiretroviral therapy. Some immune system-related genes important for this control have been identified in these patients.
People living with HIV who are 18 years of age and older, documented or suspected long-term nonprogressors in generally good health may be eligible to screen for the study.
Participants will undergo apheresis (a method for collecting larger quantities of certain blood components than can safely be collected through a simple blood draw) if venous access is adequate once yearly. Some may be asked to return every six months.
- Automated apheresis - Blood is drawn through a needle placed in an arm vein and spun in a machine, separating the blood components. The white cells are extracted and the red cells, with or without plasma (liquid part of the blood), are re-infused into the donor through a needle in the other arm. An anticoagulant (medication to prevent blood from clotting) is usually added to the blood while in the machine to prevent it from clotting during processing.
- Blood draw - a needle placed in an arm vein for large volume (approx 75ml) blood draw if veins considered inadequate for apheresis procedure.
Some of the blood collected through apheresis may be stored for future studies of HIV disease and immune function and for HLA testing, a genetic test of markers of the immune system.
Detailed Description
In an attempt to elucidate the mechanism(s) of immune-mediated restriction of HIV viral replication, we aim to study three groups of individuals: 1. People living with HIV, who appear to control HIV primarily through virus-specific cellular immunity (long-term nonprogressors/LTNP); 2. People living with HIV who have broadly cross-neutralizing antibody activity against HIV; and 3. the family members of participants exhibiting immunologic control of HIV infection. Although most of our previous efforts have focused on investigating the virus-specific immune responses in a unique group of patients termed LTNP who control HIV by cellular immune-mediated mechanisms, more recently, another group of rare individuals who naturally develop broadly cross-neutralizing antibody activity against HIV isolates have also been identified in our laboratory. Passive transfer studies in nonhuman primates have demonstrated that neutralizing antibodies detectable in a subject at the time of challenge can protect from infection. We aim to recruit more of these participants in an effort to further characterize and compare their virus-specific cellular and humoral immune responses with those in individuals experiencing progressive infection. As we attain greater insight into differences between these participant groups, we hope to perform genetic studies that would enable us to more precisely identify susceptibility or protective genes, which could be potentially used to construct a familial pedigree. We anticipate that all of these findings will contribute to an enhanced understanding of the nature of effective HIVspecific humoral and cellular immunity, which will help focus future vaccine design efforts. For our studies, it will be necessary to obtain larger quantities of plasma or mononuclear cells than can be safely obtained by simple phlebotomy. These components can be easily and safely obtained using apheresis procedures in the Clinical Center Apheresis Unit. This protocol is designed to conform to the requirements of the Apheresis Unit for donors to have leukapheresis or plasmapheresis procedures. In select participants, lymphocytes obtained from lymph node biopsy will also be studied.
Investigators
Eligibility Criteria
Inclusion Criteria
- •INCLUSION CRITERIA:
- •Adult (18 years-old or older)
- •Eligibility to undergo apheresis procedures; or, for participants who are unable to undergo apheresis, willingness to undergo blood draw for research purposes that remain within safety guidelines established by NIH policy.
- •Willingness to give informed consent for the storage of blood or tissue samples and HLA testing
- •AND at least one of the following:
- •An HIV-seropositive participant categorized as an LTNP as defined by clinical and laboratory criteria, regardless of HLA class I type.
- •HIV-seropositive progressors
- •Persons who are seronegative for HIV but are family members of seropositive participants exhibiting immunologic control of HIV
Exclusion Criteria
- •Cardiovascular instability, severe anemia, inadequate venous access, severe coagulation disorder, or any other condition that the Principal Investigator or Apheresis Unit staff considers a contraindication to the apheresis procedure or research blood draw.
- •Any condition that, in the opinion of the investigator, contraindicates participation in this study.
Arms & Interventions
Long term nonprogressors
Individuals with innate control over HIV
Family members
Family members of individuals with innate control over HIV
HIV infection with one of the following HLA types: B*27+, B*35+,B*44+, B*57+, B*58+, and/or A*02.
People living with HIV with specific HLA-types.
Outcomes
Primary Outcomes
Perform genetic studies to characterize immune-related susceptibility/protective genes and compare these between patients groups and within families.
Time Frame: Ongoing
Availability of cells from family members of LTNP with or without putative response modifiers could help in defining the role of these genes in shaping the immune response to HIV.
Identify patients with broadly neutralizing sera and characterize their HIV-specific B cell responses
Time Frame: Ongoing
characterize HIV-specific neutralizing antibody activity
Identification of the cause and effect relationships between viremia and putative immune correlates of control of HIV replication
Time Frame: Ongoing
to understand HIV-specific immunity
To further investigate differences in the virus-specific T cell-mediated responses between HIV-1-infected LTNP and patients with progressive disease who bear HLA class I alleles that have been associated with delayed disease progression and to c...
Time Frame: Ongoing
deeper understanding of the components and correlates of an effective HLA class-I-restricted HIV-specific CD8+ T cell response