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CompletedNCT00001650Updated Jul 2, 2017

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

An observational study in HIV Infection and Acquired Immunodeficiency Syndrome, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-07-02.

Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Observational

Study type
Observational
Enrollment
56
Ages
18 Years and older
Sex
All
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Study 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.

Read the detailed description

Understanding the rate of lymphocyte replication and destruction in HIV infected patients, as well as the effects of therapy on lymphocyte replication should lead to a better understanding of the mechanisms behind the immunodeficiency induced by HIV. To examine this directly, up to 85 HIV-infected patients will be enrolled in the study. Patients will receive up to two 30 minute infusions (at least one month apart) of bromodeoxyuridine (BrDU; 200 mg/m(2)), an analogue of thymidine. BrDU is incorporated into DNA and can be measured using an anti-BrDU monoclonal antibody. It can be measured in subpopulations of cells to determine the rate of replication of those cells. All participants in this study will be reimbursed for the inconvenience and discomfort associated with study participation.

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Conditions studied

  • HIV Infection
  • Acquired Immunodeficiency Syndrome

Keywords

  • BrDU
  • HIV
  • Labeling
  • CD4 Cells
  • Immunodeficiency
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In context

HIV Infections

4,258 studies on the registry are indexed under HIV Infections; 240 are open to participants now.

This study's enrollment of 56 is below the median of 200 across 713 observational studies indexed under HIV Infections.

Browse HIV Infections studies →

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,401 studies on the registry; 179 are open to participants now.

Of its 396 completed or terminated interventional studies of FDA-regulated products, 294 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

18 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.

Exclusion criteria

EXCLUSION CRITERIA:

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.

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Study design

Enrollment
56 participants (actual)
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Study locations

1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike
    Bethesda, Maryland 20892, United States
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References and documents

Publications

  • 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. PubMed 7816094 ↗
  • 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. PubMed 8929418 ↗
  • Sprent J, Tough DF. Lymphocyte life-span and memory. Science. 1994 Sep 2;265(5177):1395-400. doi: 10.1126/science.8073282. PubMed 8073282 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 2, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00001650
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
First posted
Nov 4, 1999
Start date
Sep 19, 1997
Completion
May 13, 2011
Last update
Jul 2, 2017
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in May 2011. You cannot join it, but the record below documents what was studied.

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