Protocol Number: 92-I-0125

Title:

A Study of Viral Burden in Peripheral Blood versus Lymphoid and Bone Marrow Tissue in Human Immunodeficiency Virus Infected Individuals

Number:

92-I-0125

Summary:

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.

Sponsoring Institute:

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA

1. HIV infection must be documented by a licensed ELISA and confirmed either by Western blot, positive HIV culture, positive HIV antigen, plasma viremia, or second antibody test positive by a method other than ELISA.

2. Aged 18 years or older.

3. Ability to give informed, written consent.

4. The following laboratory values:

a) Absolute neutrophil count of greater than 1000/mm3.

b) PT, PTT within normal limits.

c) 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).

d) 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. CD4+T cell count of any level.

6. Patients may be receiving anti-retroviral therapy.

7. Patients may be receiving prophylaxis for opportunistic infections.

8. HIV negative individuals will qualify as control subjects.

9. 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.

Special Instructions:

Currently Not Provided

Keywords:

Lymph Node

Polymerase Chain Reaction (PCR)

Viremia

In Situ Hybridization

AIDS

Excisional Biopsy

RNA/DNA

Recruitment Keyword(s):

None

Condition(s):

HIV Infection

Viremia

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Institute of Allergy and Infectious Diseases

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease

Studies in human immunodeficiency virus-infected individuals who are long term non-progressors

Heterozygosity for a defective gene for CC chemokine receptor 5 is not the sole determinant for the immunologic and virologic phenotype of HIV-infected long term non-progressors

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