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

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

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.

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Study Overview

• Status: Recruiting
• Conditions: HIV

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.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Daniel C Rogan, M.D.; Phone Number: (301) 642-3852; Email: daniel.rogan@nih.gov
• Study Contact Backup: Name: Rosemary McConnell, R.N.; Phone Number: (301) 761-6645; Email: rosemary.mcconnell@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals identified as having innate control over the HIV virus

Description

• 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Other

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Family members; Family members of individuals with innate control over HIV
Long term nonprogressors; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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...	deeper understanding of the components and correlates of an effective HLA class-I-restricted HIV-specific CD8+ T cell response	Ongoing
Perform genetic studies to characterize immune-related susceptibility/protective genes and compare these between patients groups and within families.	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.	Ongoing
Identify patients with broadly neutralizing sera and characterize their HIV-specific B cell responses	characterize HIV-specific neutralizing antibody activity	Ongoing
Identification of the cause and effect relationships between viremia and putative immune correlates of control of HIV replication	to understand HIV-specific immunity	Ongoing

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Daniel C Rogan, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2001

Study Registration Dates

• First Submitted: January 11, 2002
• First Submitted That Met QC Criteria: January 11, 2002
• First Posted (Estimated): January 14, 2002

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: December 7, 2023

More Information

Terms related to this study

• Keywords: Natural History; HIV Infection; Apheresis; Long-term nonprogressors; HLA B*5701
• Other Study ID Numbers: 020086; 02-I-0086

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: .Individual participant data that underline the results reported in the publication, after deidentification (text, tables, figures, and appendices)
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication
• IPD Sharing Access Criteria: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No