Viral Load in Blood and Lymph Tissues of HIV-Infected Individuals
| Status: | Recruiting |
|---|---|
| Conditions: | Infectious Disease, HIV / AIDS |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/6/2019 |
| Start Date: | March 18, 1992 |
| Contact: | Catherine A Seamon, R.N. |
| Email: | cseamon@cc.nih.gov |
| Phone: | (301) 402-3481 |
A Study of Viral Burden in Peripheral Blood Versus Lymphoid and Bone Marrow Tissue in HIV-Infected Individuals
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.
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.
We are studying the pathogenesis of HIV infection and other immune dysfunctions. Because of
the lack of an adequate animal model it is generally necessary to utilize human peripheral
blood and lymphoid tissues cells for studying aspects of either in vivo or in vitro HIV
infection. A dichotomy exists between the amount of HIV that can be measured in peripheral
blood compared to lymphoid tissue, as well as the types of immune cells that reside in each
compartment. We wish to be able to continue to elucidate many pathogenic aspects of HIV
infection and other immune dysfunctions using human peripheral blood mononuclear cells and
intact tissue or cells obtained from two major lymphoid organs, lymph nodes and bone marrow.
the lack of an adequate animal model it is generally necessary to utilize human peripheral
blood and lymphoid tissues cells for studying aspects of either in vivo or in vitro HIV
infection. A dichotomy exists between the amount of HIV that can be measured in peripheral
blood compared to lymphoid tissue, as well as the types of immune cells that reside in each
compartment. We wish to be able to continue to elucidate many pathogenic aspects of HIV
infection and other immune dysfunctions using human peripheral blood mononuclear cells and
intact tissue or cells obtained from two major lymphoid organs, lymph nodes and bone marrow.
- 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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
Click here to add this to my saved trials
