Tissue Biopsy and Imaging Studies in HIV-Infected Patients

NCT00001471 | Completed

• 2 other identifiers: 95002795-I-0027
• Study Type: observational
• Target: 386
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine tissue from the tonsils, lymph nodes and large bowel of HIV-infected patients to investigate changes in viral load and certain white blood cells during treatment. Normal volunteers and HIV-infected patients 18 years of age or older may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood and urine tests and possibly an electrocardiogram (EKG). Blood tests may include HLA typing, a genetic test of immune system markers. Participants may undergo the following procedures:

• Blood tests (patients and volunteers)
• Biopsies The frequency of biopsies for given patients may vary, depending on their specific therapy. Typically, biopsies are done at a single time, or for patients starting a new therapy, biopsies could be performed before starting therapy, during therapy and possibly after completion of therapy.
• Tonsil biopsies (patients and volunteers) Volunteers will have one tonsil biopsy. Patients will have no more than six tonsil biopsies, with no more than three in a 10-day period. The biopsy is done by an ear, nose and throat specialist as an outpatient procedure. The tonsils are numbed with a local anesthetic, and one to four pieces of tissue are extracted.
• Lymph node biopsies (patients only) Patients will have no more than four lymph node biopsies, performed no more frequently than once a month. The biopsy is done by a surgeon and may require a 2- to 3-day hospital stay. The skin above the lymph nodes is numbed with a local anesthetic, an incision is made and the tissue is removed. Alternatively, a needle biopsy may be done, in which a small amount of lymph tissue is withdrawn through a special needle injected into the site.
• Intestinal biopsies (patients and volunteers) Volunteers will have one intestinal biopsy procedure. Patients may have up to six intestinal biopsy procedures, each separated by at least 10 days. This is done by a gastroenterologist as an outpatient procedure. A flexible tube (sigmoidoscope or colonoscope) with a light and special lens at the tip is inserted into the rectum and large bowel. Wire instruments passed through the tube are used to extract small tissue samples.
• Bronchoalveolar lavage (BAL; patients and volunteers) Volunteers and patients will undergo bronchoscopy in which a flexible tube (bronchoscope) with a light and special lens at the tip is inserted through the nose or mouth into the lungs, and the lining of the lung is sampled by washing the airways with small amounts of saline. The procedure is performed by a pulmonologist or critical care specialist, usually as an outpatient.

Conditions

HIV; ICL; Healthy Volunteers

Keywords

AIDS; HIV; Retrovirus; Therapy; Response; Natural History

Outcome Measures

Primary Outcomes (1)

• Obtain lymphoid tissue by tonsillar, lymph node, or intestinal biopsies, or BAL fluid in patients with HIV, ICL, and healthy volunteers to evaluate for viral burden, lymphocyte subsets, and cytokine production.

  Evaluate for viral burden, lymphocyte subsets, and cytokine production.

  Each procedure visit where tissue is obtained.

Study Arms (3)

Healthy Volunteers

Healthy Volunteers

HIV-infected

HIV-infected individuals

ICL

Idiopathic CD4 lymphopenia

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will include patients already seen in our outpatient clinic, as well as individuals recruited from outside clinics.

You may qualify if:

• Greater than or equal to 18 years old.
• Ability to sign informed consent.
• For women of child-bearing potential, negative result on a serum or urine pregnancy test within 1 week prior to the procedure.
• Willingness to allow storage of blood or biopsy samples for possible future use to study HIV/AIDS, related diseases or the immune system; willingness to permit HLA testing.
• FOR PATIENTS UNDERGOING BIOPSIES:
• No medical contraindication to tonsillar, lymph node, or intestinal biopsy.
• For tonsillar biopsy, presence of visible tonsillar tissue; for lymph node biopsy, palpable lymph nodes.
• No aspirin or piroxicam (Feldene) for 10 days prior to the procedure; other non steroidal anti-inflammatory drugs (e.g. ibuprofen) must be discontinued the day prior to the procedure. Acetaminophen \[Tylenol\] is permitted at any time.
• FOR PATIENTS UNDERGOING BAL:
• Hematocrit greater than 27 percent, platelets greater than 50,000/ml.
• Baseline pulse-oximetry recording of 94 percent or greater unless clinical indication for bronchoscopy.
• No medical contraindication to bronchoscopy.
• In addition to the above:
• FOR HIV POSITIVE VOLUNTEERS:
• HIV infection must be confirmed by ELISA and western blot or dot blot. For patients with acute HIV infection and negative HIV serology, plasma HIV viral load greater than 10,000 copies/ml.

You may not qualify if:

• FOR ALL VOLUNTEERS UNDERGOING BIOPSIES:
• Platelet count less than 75,000 platelets/mm(3).
• PT or PTT prolonged by greater than 2 seconds unless patient has documented lupus anticoagulant/anti-phospholipid syndrome, which is not associated with an increased bleeding risk
• Known underlying bleeding disorder.
• Pregnancy.
• FOR HIV-POSITIVE OR ICL VOLUNTEERS FOR LYMPH NODE BIOPSIES:
• Use of narcotics (other than as prescribed by a physician) or cocaine less than 1 week prior to the date of biopsy.
• FOR ALL VOLUNTEERS FOR INTESTINAL BIOPSIES:
• Use of narcotics (other than as prescribed by a physician) or cocaine less than 1 week prior to the date of biopsy.
• Significant heart valve abnormalities.
• Presence of pacemaker, artificial joint or vascular surgery graft.
• FOR ALL VOLUNTEERS FOR BAL:
• Use of narcotics (other than as prescribed by a physician) or cocaine less than 1 week prior to the date of biopsy.
• Pregnancy.
• Any medical condition for which the investigators believe bronchoscopy may be contraindicated.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Zeng M, Southern PJ, Reilly CS, Beilman GJ, Chipman JG, Schacker TW, Haase AT. Lymphoid tissue damage in HIV-1 infection depletes naive T cells and limits T cell reconstitution after antiretroviral therapy. PLoS Pathog. 2012 Jan;8(1):e1002437. doi: 10.1371/journal.ppat.1002437. Epub 2012 Jan 5.

  PMID: 22241988 BACKGROUND

• Brenchley JM, Schacker TW, Ruff LE, Price DA, Taylor JH, Beilman GJ, Nguyen PL, Khoruts A, Larson M, Haase AT, Douek DC. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med. 2004 Sep 20;200(6):749-59. doi: 10.1084/jem.20040874. Epub 2004 Sep 13.

  PMID: 15365096 BACKGROUND

• Mavigner M, Cazabat M, Dubois M, L'Faqihi FE, Requena M, Pasquier C, Klopp P, Amar J, Alric L, Barange K, Vinel JP, Marchou B, Massip P, Izopet J, Delobel P. Altered CD4+ T cell homing to the gut impairs mucosal immune reconstitution in treated HIV-infected individuals. J Clin Invest. 2012 Jan;122(1):62-9. doi: 10.1172/JCI59011. Epub 2011 Dec 12.

  PMID: 22156200 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Joseph A Kovacs, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: November 30, 1994
• Last Updated: April 28, 2026

Record last verified: 2026-03-26

Locations

US (1)