IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. 
Viral Load in Blood and Lymph Tissues of HIV-Infected Individuals
This study is currently recruiting participants.
Verified July 12, 2017 by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier:
NCT00001316
First received: November 3, 1999
Last updated: July 13, 2017
Last verified: July 12, 2017
| Tracking Information | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| First Received Date ICMJE | November 3, 1999 | ||||||||
| Last Updated Date | July 13, 2017 | ||||||||
| Start Date ICMJE | March 18, 1992 | ||||||||
| Primary Completion Date | Not Provided | ||||||||
| Current Primary Outcome Measures ICMJE |
|
||||||||
| Original Primary Outcome Measures ICMJE | Not Provided | ||||||||
| Change History | Complete list of historical versions of study NCT00001316 on ClinicalTrials.gov Archive Site | ||||||||
| Current Secondary Outcome Measures ICMJE | Not Provided | ||||||||
| Original Secondary Outcome Measures ICMJE | Not Provided | ||||||||
| Current Other Outcome Measures ICMJE | Not Provided | ||||||||
| Original Other Outcome Measures ICMJE | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | Viral Load in Blood and Lymph Tissues of HIV-Infected Individuals | ||||||||
| Official Title ICMJE | A Study of Viral Burden in Peripheral Blood Versus Lymphoid and Bone Marrow Tissue in HIV-Infected Individuals | ||||||||
| Brief 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. | ||||||||
| Detailed Description | Several years ago, we and others demonstrated that lymph nodes are a major reservoir for human immunodeficiency virus (HIV) and a major site of active virus replication in infected individuals. Subsequent studies from our group showed that virologic cross talk between B cells and CD4+ T cells occurs within the microenvironment of lymphoid tissues (LT), and that immunosuppressive CD25+CD4+ regulatory T (Treg) cells enriched in the LT. Furthermore, Treg cells isolated from the LT are particularly effective in suppressing HIV-specific cytolytic activity. More recently, follicular helper (Tfh) CD4+ T cells have been described in LT and found to play an important role in providing help to B cells during germinal center reactions. These Tfh cells are expanded in HIV-infected viremic individuals and their numbers correlate with frequencies of germinal center B cells, consistent with longstanding observations of HIV-induced GC hyperplasia in untreated infected individuals. Despite the increased frequencies of Tfh and GC B cells in LT, there is also evidence for reduced immune function due to over-expression of negative regulatory molecules. 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. Given the paucity of Tfh and GC B cells in the 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 (BM) tissue. In this regard, the BM is both the site of B-cell development and the only known long-lived repository of plasma cells that are responsible for maintaining humoral immunity. While HIV infection has been shown to impair hematopoiesis in the BM, relatively little is known regarding the effect of HIV infection on plasma cells that home back to the BM after maturation. | ||||||||
| Study Type ICMJE | Observational | ||||||||
| Study Design ICMJE | Observational Model: Cohort Time Perspective: Prospective |
||||||||
| Target Follow-Up Duration | Not Provided | ||||||||
| Biospecimen | Not Provided | ||||||||
| Sampling Method | Not Provided | ||||||||
| Study Population | Not Provided | ||||||||
| Condition ICMJE | HIV Infection | ||||||||
| Intervention ICMJE | Not Provided | ||||||||
| Study Groups/Cohorts | Not Provided | ||||||||
| Publications * |
|
||||||||
|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||||
| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Recruiting | ||||||||
| Estimated Enrollment ICMJE | 400 | ||||||||
| Completion Date | Not Provided | ||||||||
| Primary Completion Date | Not Provided | ||||||||
| Eligibility Criteria ICMJE |
EXCLUSION CRITERIA:
|
||||||||
| Sex/Gender |
|
||||||||
| Ages | 18 Years and older (Adult, Senior) | ||||||||
| Accepts Healthy Volunteers | Yes | ||||||||
| Contacts ICMJE |
|
||||||||
| Listed Location Countries ICMJE | United States | ||||||||
| Removed Location Countries | Belgium | ||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT00001316 | ||||||||
| Other Study ID Numbers ICMJE | 920125 92-I-0125 |
||||||||
| Has Data Monitoring Committee | Not Provided | ||||||||
| U.S. FDA-regulated Product | Not Provided | ||||||||
| IPD Sharing Statement | Not Provided | ||||||||
| Responsible Party | National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ) | ||||||||
| Study Sponsor ICMJE | National Institute of Allergy and Infectious Diseases (NIAID) | ||||||||
| Collaborators ICMJE | Not Provided | ||||||||
| Investigators ICMJE |
|
||||||||
| PRS Account | National Institutes of Health Clinical Center (CC) | ||||||||
| Verification Date | July 12, 2017 | ||||||||
|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
|||||||||