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 B*57+, B*27+ 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 B*57+, B*27+ 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. ...

Population

Individuals identified as having innate control over the HIV virus

Brief Title

Leukapheresis to Obtain Plasma or Lymphocytes for Studies of HIV-infected Patients, Including Long-term Non-progressors

Official Title

Evaluation of Viral Factors and Immune Parameters to Study HIV-Specific Immunity

Brief Summary

This study will collect white blood cells and plasma for research on how the immune system <br /> controls HIV infection. The immune system of a very small group of HIV-infected patients, <br /> called non-progressors, has been able to control HIV for long periods without antiretroviral <br /> therapy. Some immune system-related genes important for this control have been identified in <br /> these patients. This study will examine the contribution of HLA genes B*57+, B*27+ and A*01+ <br /> to HIV disease in progressors and long-term non-progressors. (HLA type is a genetic marker of <br /> the immune system.) <br /> <br /> HIV-infected patients 18 years of age and older with HLA types B*57+, B*27+ and/or A*01+ may <br /> be eligible for this study. <br /> <br /> Participants will undergo apheresis-a method for collecting larger quantities of certain <br /> blood components than can safely be collected through a simple blood draw-by one of the <br /> following two methods: <br /> <br /> - Automated pheresis - Blood is drawn through a needle placed in an arm vein and spun in a <br /> machine, separating the blood components. The white cells are extracted and the red <br /> cells, with or without plasma (liquid part of the blood), are re-infused into the donor <br /> through the same needle or a needle in the other arm. An anticoagulant (medication to <br /> prevent blood from clotting) is usually added to the blood while in the machine to <br /> prevent it from clotting during processing. <br /> <br /> - Manual pheresis - One unit (1 pint) of blood is drawn through a needle placed in an arm <br /> vein, similar to donating a pint of whole blood. The red blood cells, with or without <br /> plasma, are separated from the rest of the blood and re-infused to the donor through the <br /> same needle. Manual pheresis will be done only when a person s estimated total blood <br /> volume or red cell count is too low to safely permit removal of blood through a pheresis <br /> machine. An adult small in size or markedly anemic, for example, may fall into this <br /> category. <br /> <br /> Some of the blood collected through apheresis may be stored for future studies of HIV disease <br /> and immune function and for HLA testing, a genetic test of markers of the immune system. Some <br /> of the blood may be used to screen for different types of viral liver infections, such as <br /> hepatitis A, B, C, D, E, F, or G. <br /> <br /> ...

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) HIV-infected long-term
nonprogressors (LTNP), who appear to control HIV primarily through virus-specific cellular
immunity; 2) HIV-infected participants 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 subjects, lymphocytes obtained from lymph node biopsy
will also be studied.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.