Overview
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 HIV-infected patients, 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. This study will examine the contribution of HLA genes B57+, B27+ and A*01+ to HIV disease in progressors and long-term non-progressors. (HLA type is a genetic marker of the immune system.)
HIV-infected patients 18 years of age and older with HLA types B57+, B27+ and/or A*01+ may be eligible for this 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-by one of the following two methods:
- Automated pheresis - 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 the same needle or 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.
- Manual pheresis - One unit (1 pint) of blood is drawn through a needle placed in an arm vein, similar to donating a pint of whole blood. The red blood cells, with or without plasma, are separated from the rest of the blood and re-infused to the donor through the same needle. Manual pheresis will be done only when a person s estimated total blood volume or red cell count is too low to safely permit removal of blood through a pheresis machine. An adult small in size or markedly anemic, for example, may fall into this category.
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. Some of the blood may be used to screen for different types of viral liver infections, such as hepatitis A, B, C, D, E, F, or G.
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:
- People living with HIV, who appear to control HIV primarily through virus-specific cellular immunity (long-term nonprogressors/LTNP);
- People living with HIV who have broadly cross-neutralizing antibody activity against HIV; and
- 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.
Eligibility
- 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:
- Pregnant
- 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.