Use of Bromodeoxyuridine to Study White Blood Cell Replication and Survival in HIV-Infected Patients

NCT00001650 | Completed

• 2 other identifiers: 97018997-I-0189
• Study Type: observational
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine how quickly white blood cells called CD4 lymphocytes reproduce and how long they live in people infected with HIV. It will do this using bromodeoxyuridine (BrDU), a compound that is structurally similar to thymidine, one of the building blocks of DNA. BrDU gets incorporated into DNA instead of thymidine, but it can only get into cells that are replicating. Therefore, measuring the proportion of cells with BrDU indicates how many cells are replicating. HIV-infected patients 18 years of age and older may be eligible for this study. Candidates will be screened with a medical history, physical examination, chest X-ray, electrocardiogram (EKG) and blood tests. Participants will be given an infusion of BrDU through a catheter (thin plastic tube) placed in an arm vein. Blood will be drawn up to 4 times in the first 24 hours after the infusion. Additional samples will then be collected as often as daily for the first week, twice a week for the next 3 weeks and then weekly to monthly for up to 1 year. Some patients may undergo a tissue biopsy (removal of a small tissue sample from a lymph node, tonsil or colon) or computed tomography (CT) scans of the thymus (a small gland between the lungs that manufactures lymphocytes. Some patients will have a second infusion in order to examine changes in the rate of CD4 replication over time or following potent antiretroviral therapy. Patients will be followed in the clinic periodically for the first year and then will be seen in the clinic or contacted by telephone once a year for 4 more years. The results of this study may provide a better understanding of how HIV causes disease and how therapy affects the immune system.

Conditions

HIV Infection; Acquired Immunodeficiency Syndrome

Keywords

BrDU; HIV; Labeling; CD4 Cells; Immunodeficiency

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older.
• Documented HIV infection (ELISA/Western blot positive or, for acute seroconverters, PCR positive).
• Able to provide informed consent and willing to comply with study requirements and clinic policies.
• Negative urine or serum pregnancy test (for women of childbearing potential). In addition, women of childbearing potential must agree to practice abstinence or use two methods of birth control / contraception for 4 weeks prior to and 2 weeks after each BrDU infusion. Similarly, all men must agree to practice abstinence or use a condom when engaging in intercourse during the same time period.
• Hemoglobin greater than 9 mg/dl; platelets greater than 50,000/mm(3); neutrophils greater than 750 cells/mm(3).
• AST/ALT less than 300 IU/ml.
• Less than Grade 2 level toxicity for other laboratory parameters.

You may not qualify if:

• Active substance abuse or prior history of substance abuse which may interfere with protocol compliance.
• Psychiatric illness or disturbance which, in the assessment of the protocol team, may affect safety or compliance.
• Significant underlying cardiac, pulmonary, renal, gastrointestinal, rheumatologic or CNS disease as detectable on routine history, physical exam, or screening laboratory studies.
• Pregnancy or breast-feeding.
• Ongoing therapy with topical or systemic 5-fluorouracil.
• Willingness to allow stored samples to be used for future studies of HIV infections and immunological function, and willingness to have HLA typing performed.
• Patients who are virologic responders and immunologic non-responders (10-15 patients):
• Plasma HIV less than 500 copies/ml by bDNA or RT-PCR for 1 year while receiving HAART, which includes at a minimum 3 antiretroviral drugs, at least one of which is a protease inhibitor or non-nucleoside reverse transcriptase inhibitor, and plasma HIV less than 50 copies /ml by the bDNA assay, performed at the NIH, within the 4 weeks prior to enrollment;
• CD4 count less than 300 cells/mm(3) on 2 occasions at least one week apart, with no documented CD4 count greater than 350 cells/mm(3) during the prior 6 months;
• No ongoing opportunistic infection or malignancy.
• Patients who are virologic and immunologic responders (10-15 patients, matched if possible to study group for age (+/- 5 years) and duration of HAART therapy (+/- 6 months):
• Plasma HIV less than 500 copies/ml by bDNA or RT-PCR for 1 year while receiving HAART, which includes at a minimum 3 antiretroviral drugs, at least one of which is a protease inhibitor or non-nucleoside reverse transcriptase inhibitor, and plasma HIV less than 50 copies/ml by the bDNA assay, performed at the NIH, within the 4 weeks prior to enrollment;
• CD4 count greater than 350 cells/mm(3) on 2 occasions at least one week apart; CD4 count prior to the initiation of HAART therapy documented to be less than 300 cells/mm(3);
• No ongoing opportunistic infection or malignancy.
• For all patients: Willingness to have a CT scan of the thymus, to be performed under protocol 95-I-0027.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995 Jan 12;373(6510):123-6. doi: 10.1038/373123a0.

  PMID: 7816094 BACKGROUND

• Wolthers KC, Bea G, Wisman A, Otto SA, de Roda Husman AM, Schaft N, de Wolf F, Goudsmit J, Coutinho RA, van der Zee AG, Meyaard L, Miedema F. T cell telomere length in HIV-1 infection: no evidence for increased CD4+ T cell turnover. Science. 1996 Nov 29;274(5292):1543-7. doi: 10.1126/science.274.5292.1543.

  PMID: 8929418 BACKGROUND

• Sprent J, Tough DF. Lymphocyte life-span and memory. Science. 1994 Sep 2;265(5177):1395-400. doi: 10.1126/science.8073282.

  PMID: 8073282 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: September 19, 1997
• Study Completion: May 13, 2011
• Last Updated: July 2, 2017

Record last verified: 2011-05-13

Locations

US (1)