Viral Load in Blood and Lymph Tissues of HIV-Infected Individuals

Conditions Phase Intervention Type

Eligibility

Ages Eligible for Study
18 years and up
Genders Eligible for Study
Both

Keywords

Lymph Node, Polymerase Chain Reaction PCR, In Situ Hybridization, AIDS, and Excisional Biopsy

Sponsors

NIH
National Institute of Allergy and Infectious Diseases (NIAID)

Inclusion Criteria

1. HIV infection must be documented by a licensed ELISA and confirmed either by
Western blot, or plasma viremia.

2. Aged 18 years or older.

3. Ability to give informed, written consent.

4. The following laboratory values:

1. Absolute neutrophil count of greater than 1000/mm3.

2. PT, PTT within normal limits (unless PTT is elevated in presence of positive
lupus anticoagulant in a subject with no prior history of abnormal
bleeding).

3. Adequate blood counts (HIV positive volunteers: hemoglobin greater than or
equal to 9.0 g/dL, HCT greater than or equal to 28%, platelets greater than
or equal to 75,000; HIV negative volunteers: hemoglobin greater than or
equal to 11.2 g/dL, HCT greater than or equal to 34.1%, platelets greater
than or equal to 150,000).

4. Blood pressure less than or equal to 180/100; pulse rate 50-100, unless a
lower pulse rate is considered normal for the volunteer.

5. HIV negative individuals will qualify as control subjects.

6. Patients must have a clinically palpable lymph node in an easily accessible
location.

Exclusion Criteria

1. Women who are pregnant and/or breast-feeding.

2. Currently abusing alcohol or other drugs, including narcotics or cocaine.

3. Patients with AIDS dementia or with an AIDS related malignancy other than minimal
Kaposi's sarcoma.

4. No Aspirin or Non-Steroidal Anti-inflammatory medications (NSIADs) 7 days prior to
procedure. Acetaminophen (Tylenol) is permitted at any time.

5. Any medical condition for which the PI feels LN BX might be contraindicated.

6. Subjects in which sedation is planned. Use of narcotics (other than as prescribed by a
physician) or cocaine less than 1 week prior to the date of biopsy will be excluded.

Detailed Description

Our laboratory has previously demonstrated that lymph nodes are a major reservoir for human immunodeficiency virus (HIV) and a major site of active virus replication in infected individuals(1-3). There is at least a 10 fold greater viral burden per given number of CD4+ T lymphocytes obtained from the lymph nodes versus the peripheral blood in the same infected individual. These data have been accumulated predominantly in individuals with progressive generalized lymphadenopathy (CDC Class A1 and A2). It is unclear at present whether this pattern holds true for all categories of HIV infected individuals. We have proposed that the seeding of lymph nodes by HIV early in the course of HIV infection and the persistent production of virus in lymph nodes throughout the course of infection are major factors in the pathogenesis of HIV in virtually all infected individuals. In addition, it is likely that the selective perturbations of various T cell subsets (i.e., V-B classes of CD4+T cells) that have been observed in peripheral blood are much more dramatic in the lymph node given the greater viral burden in the lymph node compared to the peripheral blood. In order to investigate this hypothesis, it is essential that we study simultaneously lymph nodes and peripheral blood from the same individuals and that we study different individuals at various stages of disease from early in the course of infection (CDC Class A) to advanced disease (CDC Class B and C). If, as we suspect, there is active virus replication in the lymph node early in the course of infection, even at a time when there is little virus burden or active replication in the peripheral blood, this would justify anti-retroviral therapy at the earliest possible time in the course of infection. In addition, in certain patients who are about to initiate treatment with an anti-retroviral agent such as zidovudine or didanosine through their private physician, it would be important to know whether treatment actually reduces the viral burden and virus replication in lymph nodes. The effect of therapy on viral burden and replication will be compared in the lymph node versus peripheral blood mononuclear cells and both of these parameters will be compared with the level of plasma viremia.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001316

Overall Contact

Susan Moir, Ph.D.
(301) 402-4559

Overall Contact Backup

Catherine A Seamon, R.N.
(301) 402-3481

Locations

  • National Institutes of Health Clinical Center, 9000 Rockville Pike
    Bethesda, Maryland United States

    Status: Recruiting

    Contact info For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
    800-411-1222xTTY8664111010