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.

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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.

• INCLUSION CRITERIA:

  1. Adult (18 years-old or older)
  2. 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.
  3. 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:

1. Pregnant
2. 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.
3. Any condition that, in the opinion of the investigator, contraindicates participation in this study.

Individuals identified as having innate control over the HIV virus

Individual participant data that underline the results reported in the publication, after de-identification (text, tables, figures, and appendices)

Beginning 9 months and ending 36 months following article publication

Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose. Analysis for individual participant data meta-analysis. Proposals may be submitted up to 36 months following article publication.