A Pilot Study of the Patterns of Cellular Gene Expression in HIV-1 Patients Following Clinical Events Which Increase Plasma Virus Concentrations

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001681
First received: November 3, 1999
Last updated: March 3, 2008
Last verified: October 1999
  Purpose

The factors that influence HIV disease progression are not well understood. While larger amounts of circulating virus (high 'viral loads') predict future adverse clinical events, many of the clinical factors responsible for high viral loads and disease progression remain unknown. Certain clinical events and defined interventions are associated with increases in plasma viral RNA concentrations. One of these clinical interventions is immunization; immunization with several vaccines have been shown to increase plasma HIV RNA concentrations. Even though vaccination can lead to transient increases in plasma HIV concentrations, certain vaccines, including influenza vaccine, are still recommended for HIV patients because the risks of the disease targeted by the immunization are held to be greater than the immunization itself. Therefore, immunization with influenza vaccine can be considered a model, clinically indicated intervention, given at a known time which stimulates HIV replication. For influenza immunization, and for other treatments leading to increases in viral RNA concentrations is not available. We hypothesize that immunization with influenza vaccine, and perhaps other immune stimulatory events, lead to an increase in HIV replication through a regulatory system involving cytokines, signal transduction systems, transcription factors, effects on the cell cycle, and increased expression of additional gene products needed for viral replication, such as genes of the nucleic acid biosynthetic pathways. While experiments aimed at investigating one or another particular part of this regulatory system can be performed with traditionally available technologies, such technologies cannot provide comprehensive information concerning a large number of the regulatory events that may be involved in mediating the increase in HIV RNA concentration. In this protocol, we aim to develop the methodologies needed to determine changes in expression of many of the genes which may be involved in mediating the regulation of HIV expression in HIV-infected patients using cDNA microarray technologies. Once the methodologies are developed, such work may provide new insights into the regulatory systems controlling HIV expression in HIV-infected patients may provide new insights into the pathogenesis of HIV disease.


Condition
HIV Infections

Study Type: Observational
Official Title: A Pilot Study of the Patterns of Cellular Gene Expression in HIV-1 Patients Following Clinical Events Which Increase Plasma Virus Concentrations

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 40
Study Start Date: October 1997
Estimated Study Completion Date: September 2000
Detailed Description:

The factors that influence HIV disease progression are not well understood. While larger amounts of circulating virus (high 'viral loads') predict future adverse clinical events, many of the clinical factors responsible for high viral loads and disease progression remain unknown. Certain clinical events and defined interventions are associated with increases in plasma viral RNA concentrations. One of these clinical interventions is immunization; immunization with several vaccines have been shown to increase plasma HIV RNA concentrations. Even though vaccination can lead to transient increases in plasma HIV concentrations, certain vaccines, including influenza vaccine, are still recommended for HIV patients because the risks of the disease targeted by the immunization are held to be greater than the immunization itself. Therefore, immunization with influenza vaccine can be considered a model, clinically indicated intervention, given at a known time which stimulates HIV replication. For influenza immunization, and for other treatments leading to increases in viral RNA concentrations, detailed knowledge of the regulatory events that mediate the increase in RNA concentrations is not available. We hypothesize that immunization with influenza vaccine, and perhaps other immune stimulatory events, lead to an increase in HIV replication through a regulatory system involving cytokines, signal transduction systems, transcription factors, effects on the cell cycle, and increased expression of additional gene products needed for viral replication, such as genes of the nucleic acid biosynthetic pathways. While experiments aimed at investigating one or another particular part of this regulatory system can be performed with traditionally available technologies, such technologies cannot provide comprehensive information concerning a large number of the regulatory events that may be involved in mediating the increase in HIV RNA concentration. In this protocol, we aim to develop the methodologies needed to determine changes in expression of many of the genes which may be involved in mediating the regulation of HIV expression in HIV-infected patients using cDNA microarray technologies. Once the methodologies are developed, such work may provide new insights into the regulatory systems controlling HIV expression in HIV-infected patients may provide new insights into the pathogenesis of HIV disease.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

PATIENT VOLUNTEERS:

HIV positive.

CD4 cells greater than 200, obtained within the prior 2 months.

Age greater than 18 years.

Willing and able to participate in study.

No immunomodulatory therapy, including other vaccinations within the prior 4 weeks. Stable therapy on G-CSF and/or thalidomide permitted.

No contraindications for influenza vaccination.

No clinical conditions that would place the patient at undo risk from the mandated protocol blood draws.

No recent (less than 4 weeks) changes in antiviral therapy or change in antiviral therapy anticipated during the 3 week duration of the study.

No history of recent (less than 4 weeks) or intercurrent blood transfusion or cytotoxic chemotherapy.

Hemoglobin greater than 9.0 g/dl.

Total volume of blood otherwise drawn should not exceed 500 ml over 6 weeks.

No upper respiratory infections or other acute illnesses within the prior 2 weeks.

CONTROL NORMAL VOLUNTEERS:

Age greater than 18 years.

Willing and able to participate in study.

Healthy.

No ongoing condition or recent (less than 4 weeks) illness requiring a physician's care.

No upper respiratory infections or other acute illnesses within the prior 2 weeks.

Total volume of blood drawn should not exceed 500 ml over 6 weeks.

Not taking any prescription medications.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001681

Locations
United States, Maryland
National Cancer Institute (NCI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00001681     History of Changes
Other Study ID Numbers: 980011, 98-C-0011
Study First Received: November 3, 1999
Last Updated: March 3, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Cytokines
Gene Regulation
Immunization
Influenza
Pathogenesis

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on July 23, 2014