Studies of the Pathogenesis of HIV Infection in Human Peripheral Blood Cells and/or Body Fluids in People Living With and Without HIV

The purpose of this this study is to learn more about the immune system, how it responds to infections (like HIV) and to learn more about conditions that may decrease your immune system s ability to fight infections. The primary procedure to be performed is venipuncture and blood drawing. The blood will be used for a variety of studies looking at immune dysfunctions and at the effects of HIV or other infectious and noninfectious conditions on the production of factors by immune cells. In addition, the cells in the blood may be screened for genes that have missing pieces or changes in them that can affect their function. This will help us evaluate specific immune responses for research purposes. This study will examine the effects of HIV infection on substances produced by immune cells that increase or decrease HIV infection.

Both people living with and without HIV may be eligible for this study. Participants will be required to have a yearly medical evaluation, including blood tests for cell counts and chemistries, a blood or urine pregnancy test for women, and other laboratory tests as medically indicated or for research purposes.

Participants will donate blood or reproductive fluids, or both. From 20 to 150 cc (4 to 30 teaspoonfuls) of blood will be drawn from the arm using a small needle. Participants may be asked to provide blood samples on more than one occasion over the course of the study. No more than 450 cc (less than 1 pint) of blood will be drawn during any 6-week period. Males will be given a private room for semen donation; fluid from females will be collected with a cotton swab after speculum insertion. Participants may also be asked to have a buccal swab. For this procedure, the inside of the cheek is gently scraped with a blunt-ended stick or brush to obtain cells (buccal mucosal cells). The tissues will be used for a variety of studies on the effects of HIV infection on factors that increase or decrease HIV infection.

Some of the tissues collected for this study may also be used for the following tests:

• Hepatitis screening Blood may be screened for different types of viral liver infections, such as hepatitis A, B, C, D, E, or G.
• Genetic testing We will use genetic tests that focus on specific genes that can affect how the immune system works or to learn more about HIV and other conditions being studied. We may test the DNA in the cells in the blood or in cheek cells for the presence of mutations or deletions. These alterations may be sought in genes encoding factors that are linked to the immune system s ability to fight infection and prevent disease, or factors that allow HIV and other infectious agents to cause infection. from blood or cheek cells may be examined for mutations or deletions that affect chemokines, cytokines and a family of enzymes called caspases. Chemokines and cytokines are important mediators of the immune response. Alterations in the genes for some of these substances influence HIV infection.
• HLA testing Blood may be tested for HLA type-a genetic marker of the immune system. These tests may be used to try to identify factors associated with the rate of progression of HIV disease or related conditions. Determining HLA type is necessary to be able to perform certain research studies. Some HLA types have been associated with an increased risk of certain diseases like arthritis and other rheumatologic problems.

Study Overview

• Status: Recruiting
• Conditions: HIV; Infectious Diseases; Immunodeficiencies

Detailed Description

We are studying virologic and/or immunologic parameters of HIV infection and other infectious or non-infectious immune deficiency diseases in order to better understand the pathogenesis of HIV. Because of the lack of an adequate animal model it is generally necessary to utilize human peripheral blood cells for studying aspects of either in vivo or in vitro HIV infection. We wish to be able to continue to elucidate many pathogenic aspects of HIV infection in relation to other infectious or non-infectious immune regulation and dysregulation using human peripheral blood mononuclear cells as a model.

• Study Type: Observational
• Enrollment (Estimated): 2500

Contacts and Locations

• Study Contact: Name: Catherine A Seamon, R.N.; Phone Number: (301) 402-3481; Email: cseamon@cc.nih.gov
• Study Contact Backup: Name: Susan Moir, Ph.D.; Phone Number: (301) 402-4559; Email: sm221a@nih.gov

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Completed
      • Washington Hospital Center
  • 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: Yes

• Sampling Method: Non-Probability Sample

Study Population

Volunteers living with/without HIV, Volunteers with/without immunodeficiencies, Volunteers with/without infectious diseases of interest

Description

• INCLUSION CRITERIA:
• 18 years of age or older.
• Adequate venous access.
• Have a blood pressure less than or equal to 180/100: pulse rate 50-100, unless a lower pulse rate is considered normal for the volunteer.
• Have adequate blood counts (volunteers living with HIV: hemoglobin greater than or equal to 9.0 g/dL, platelets greater than or equal to 50,000; volunteers living without HIV: hemoglobin greater than or equal to 9.0 g/dL, platelets greater than or equal to 50,000
• Be willing and able to provide written informed consent on screening, comply with study requirements and procedures, and comply with clinic policies
• Willingness to allow blood samples to be used for future studies of HIV infection/pathogenesis, and undergo hepatitis screening

EXCLUSION CRITERIA:

• Pregnant and/or breastfeeding females.
• Active substance abuse or history of prior substance abuse that may interfere with protocol compliance or compromise patient safety.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Individuals with/without Immunodeficiencies; Individuals with/without immunodeficiencies
Individuals living with HIV
Individuals living with/without HIV
Individuals living with/without infectious diseases; Individuals living with/without infectious diseases of interest

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The purpose of this protocol is to provide a mechanism to obtain blood products and other biologic samples that will be used by NIH Intramural Investigators in studies of HIV and other infectious or immune deficiency diseases	To provide a mechanism to obtain blood products and other biologic samples that will be used by NIH Intramural Investigators in studies of HIV and other infectious or immune deficiency diseases.	Throughout

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To provide the opportunity to compare genomic and proteomic properties of specimens obtained from individuals living with HIV, other infectious diseases, and other immunodeficiencies with those of healthy volunteers	To provide the opportunity to compare genomic and proteomic properties of specimens obtained from individuals living with HIV, other infectious diseases, and other immunodeficiencies with those of healthy volunteers	Throughout

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Medstar Health Research Institute
• Investigators: Principal Investigator: Susan Moir, Ph.D., National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

General Publications

• Le Saout C, Hasley RB, Imamichi H, Tcheung L, Hu Z, Luckey MA, Park JH, Durum SK, Smith M, Rupert AW, Sneller MC, Lane HC, Catalfamo M. Chronic exposure to type-I IFN under lymphopenic conditions alters CD4 T cell homeostasis. PLoS Pathog. 2014 Mar 6;10(3):e1003976. doi: 10.1371/journal.ppat.1003976. eCollection 2014 Mar.
• Jelicic K, Cimbro R, Nawaz F, Huang da W, Zheng X, Yang J, Lempicki RA, Pascuccio M, Van Ryk D, Schwing C, Hiatt J, Okwara N, Wei D, Roby G, David A, Hwang IY, Kehrl JH, Arthos J, Cicala C, Fauci AS. The HIV-1 envelope protein gp120 impairs B cell proliferation by inducing TGF-beta1 production and FcRL4 expression. Nat Immunol. 2013 Dec;14(12):1256-65. doi: 10.1038/ni.2746. Epub 2013 Oct 27.
• Auerbach DJ, Lin Y, Miao H, Cimbro R, Difiore MJ, Gianolini ME, Furci L, Biswas P, Fauci AS, Lusso P. Identification of the platelet-derived chemokine CXCL4/PF-4 as a broad-spectrum HIV-1 inhibitor. Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9569-74. doi: 10.1073/pnas.1207314109. Epub 2012 May 29.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 1993

Study Registration Dates

• First Submitted: November 3, 1999
• First Submitted That Met QC Criteria: November 3, 1999
• First Posted (Estimated): November 4, 1999

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: February 9, 2024

More Information

Terms related to this study

• Keywords: Natural History; Lymphocytes; Venipuncture; Mononuclear Cells
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Urogenital Diseases; Genital Diseases; HIV Infections; Infections; Communicable Diseases
• Other Study ID Numbers: 910140; 91-I-0140

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: .Identified data in BTRIS (automatic for activities in the Clinical Center).@@@@@@@@@@@@De-identified or identified data with approved outside collaborators under appropriate agreements.@@@@@@@@@@@@This study will comply with the NIH Genomic Data Sharing Policy, which applies to all NIH-funded research that generates large-scale human or non-human genomic data, as well as the use of these data for subsequent research. Large-scale data include genome-wide association studies (GWAS), single nucleotide polymorphisms (SNP) arrays, and genome sequence, transcriptomic, epigenomic, and gene expression data. De-identified data may be shared in an NIH-funded or approved public repositories, including the Database of Genotypes and Phenotypes (dbGAP) or in NCBI Virus Portal for viral sequencing.
• IPD Sharing Time Frame: Shared scientific data should be made accessible as soon as possible, and no later than the time of an associated publication, or the end of the award/support period, whichever comes first.@@@@@@@@@@@@Genomic data will be shared following the guidelines of the Genomic Data Sharing Policy, when applicable.
• IPD Sharing Access Criteria: Identified data in BTRIS (automatic for activities in the Clinical Center and will be available for use following the BTRIS Policy for Data Sharing and Use).@@@@@@@@@@@@De-identified or identified data with approved outside collaborators under appropriate agreements.@@@@@@@@@@@@De-identified genomic data may be shared in an NIH-funded or approved public repositories, including the Database of Genotypes and Phenotypes (dbGAP) or in NCBI Virus Portal for viral sequencing and the use of the data within will be governed by their policies.
• 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