View Clinical Trial (Medical Research Study)
A Study of Viral Burden in Peripheral Blood Versus Lymphoid and Bone Marrow Tissue in HIV-Infected Individuals
| City: |
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Bethesda |
| State: |
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Maryland |
| Zip Code: |
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20892 |
| Conditions: |
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HIV Infection - Viremia |
| Purpose: |
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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.
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| Study Summary: |
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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. Several subsequent studies have shown that virologic cross talk between B
cells and CD4+ T cells occurs within the microenvironment of lymphoid tissues (LT) and, to a
lesser extent, between cells in lymph nodes and the peripheral blood. Recently we have
demonstrated that immunosuppressive CD25+CD4+ regulatory T (Treg) cells are enriched to the
LT, compared to the blood, of viremic HIV+ subjects. Furthermore, Treg cells isolated from
the LT are particularly effective in suppressing HIV-specific cytolytic activity. We are
currently investigating several issues related to the impact of HIV infection/replication on
the immune competence and homing profiles of numerous cell types within the LT. In
particular, we are also investigating the role of the negative regulatory molecules,
programmed death (PD)-1 and its ligands PD-L1 and PD-L2, in the suppression of HIV-specific
T cell responses and the induction of apoptosis. The interaction between PD-1 and its
ligands is thought to be a major mechanism whereby T cell effector function in tissue sites
is restrained. Therefore, while we have performed functional studies in this area using
peripheral blood, these studies are more appropriately conducted with tissue samples. We
will also pursue immunological, migrational and virologic characteristics of various cell
types including B cells and their subsets and CD4+, CD8+, and NK cells in the LT and bone
marrow tissue.
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| Criteria: |
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- 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.
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 12.0 g/dL, HCT greater than or equal to 38%, 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. Patients who have taken more than two 650 mg doses of aspirin less than one week
prior to the date of biopsy.
5. Patients who have taken non-aspirin containing, non-steroidal, anti-inflammatory
medications (e.g. ibuprofen, naproxen, and similar drugs) within 24 hours prior to
the date of biopsy.
6. Any medical condition for which the PI feels LN BX might be contraindicated.
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| NCT ID: |
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NCT00001316 |
| Primary Contact: |
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Principal Investigator
Susan Moir, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Laura A Heytens
Phone: (301) 435-8003
Email: heytensl@mail.nih.gov
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| Backup Contact: |
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Email: sm221a@nih.gov
Susan Moir, Ph.D.
Phone: (301) 402-4559
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| Location Contact: |
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Bethesda, Maryland 20892
United States
For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)
Phone: 800-411-1222
Email: prpl@mail.cc.nih.gov
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 23, 2013 |
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