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

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.

- 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:

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.