The Effectiveness of GM-CSF in HIV-Positive Patients Who Are Also Receiving Anti-HIV Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000850
First received: November 2, 1999
Last updated: May 16, 2012
Last verified: May 2012
  Purpose

The purpose of this study is to see how HIV-positive patients who are taking anti-HIV drugs and have a viral load (level of HIV in the blood) of 1,500 copies/ml or more respond to GM-CSF (granulocyte-macrophage colony-stimulating factor).

GM-CSF is a medication that is being tested in HIV-positive patients to see if it can improve their immune systems or if it can lower the level of HIV in their blood. GM-CSF is often given to patients with leukemia or patients who have received bone marrow transplants to increase their white blood cells and to improve their immune systems. Doctors believe that GM-CSF can increase CD4 counts in HIV-positive patients, but this study will also look at how GM-CSF affects viral load.


Condition Intervention Phase
HIV Infections
Drug: Indinavir sulfate
Drug: Sargramostim
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Primary Purpose: Treatment
Official Title: The Effects of GM-CSF on Plasma HIV-1 RNA and Chemokine Receptor Expression in HIV-1 Infected Subjects Receiving Concomitant Potent Antiretroviral Therapy

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 108
Study Completion Date: December 2003
Detailed Description:

GM-CSF promotes the differentiation and activation of granulocytes, monocytes, macrophages, and dendritic cells and enhances the function of these cells. The various cellular responses (i.e., division, maturation, activation) are induced when GM-CSF binds to specific receptors expressed on the surface of target cells. At higher doses, such as the dose used in this protocol, GM-CSF may result in a rapid rise in white blood cell count. However, further research is necessary to determine the potential antiviral effect of GM-CSF in a potent ART-treated population. It is hoped that GM-CSF can decrease the extent of ongoing HIV replication via alteration of macrophage activation and chemokine receptor expression and that this effect can result in reduction of the pool of latently infected T cells.

Patients are stratified at study entry according to screening CD4 count (below 200 cells/mm3 versus 200 cells/mm3 or higher) and screening HIV-1 RNA copy number (between 1,500 and 10,000 versus 10,000 copies/ml or higher). Then, patients are randomized to receive GM-CSF or GM-CSF placebo subcutaneously 3 times per week for 16 weeks. All patients remain on their current stable potent ART (not provided by this study). During Step 2, all patients receive open-label study treatment, consisting of current potent ART plus GM-CSF subcutaneously 3 times per week for 32 additional weeks. HIV-1 RNA, CD4 counts, and clinical and safety parameters are monitored for all patients periodically until Week 52. Patients who experience an increase in HIV-1 RNA of greater than 1 log 10 from baseline on 2 consecutive determinations or a greater than 50% decrease in CD4 count from baseline (a drop of at least 50 cells) on 2 consecutive determinations at any time during Step 1 or 2 must discontinue all study treatment. Patients who discontinue study treatment for any reason prior to Week 16 continue following the study visit schedule through Week 16.

Additional laboratory samples are performed on patients participating in the immunology substudy (ACTG A5042s) in order to further evaluate the effects of GM-CSF on immune function.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patients may be eligible for this study if they:

  • Are HIV-positive.
  • Have a stable viral load of at least 1,500 copies/ml within 30 days of study entry.
  • Are on stable aggressive anti-HIV therapy for at least 8 weeks before study entry and intend to remain on this therapy during the study.
  • Agree to learn how to give themselves the GM-CSF shots.
  • Agree to practice acceptable barrier methods of birth control (such as condoms) during the study and for at least 12 weeks after treatment ends.
  • Are at least 18 years old.

Exclusion Criteria

Patients will not be eligible for this study if they:

  • Have an infection or other illness within 14 days of study entry.
  • Have certain types of hepatitis within 30 days of study entry.
  • Have a fever or chronic diarrhea within 30 days of study entry.
  • Have cancer (except for certain types of Kaposi's sarcoma).
  • Have heart disease.
  • Are allergic to GM-CSF.
  • Have received certain medications.
  • Are pregnant or breast-feeding.
  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: NCT00000850

  Show 39 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Jeffrey Jacobson
Study Chair: Gail Skowron
Study Chair: Pablo Tebas
Study Chair: Hernan Valdez
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000850     History of Changes
Other Study ID Numbers: A5041, AACTG A5041, 10887, ACTG A5041
Study First Received: November 2, 1999
Last Updated: May 16, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV-1
Granulocyte-Macrophage Colony-Stimulating Factor
RNA, Viral
Anti-HIV Agents
Viral Load
Receptors, Chemokine

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
Indinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 22, 2014