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

The Effects of GM-CSF on Plasma HIV-1 RNA and Chemokine Receptor Expression in HIV-1 Infected Subjects Receiving Concomitant Potent Antiretroviral Therapy

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Indinavir sulfate; Drug: Sargramostim

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.

• Study Type: Interventional
• Enrollment: 108
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Univ of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90095
      • UCLA CARE Ctr
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente LAMC
    • Menlo Park, California, United States, 94025
      • Willow Clinic
    • San Diego, California, United States, 921036325
      • Univ of California / San Diego Treatment Ctr
    • San Francisco, California, United States, 941102859
      • San Francisco Gen Hosp
    • San Jose, California, United States, 951282699
      • Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
    • San Rafael, California, United States, 94903
      • Marin County Specialty Clinic
    • Stanford, California, United States, 943055107
      • San Mateo AIDS Program / Stanford Univ
    • Stanford, California, United States, 943055107
      • Stanford Univ Med Ctr
    • Torrance, California, United States, 90502
      • Harbor UCLA Med Ctr
  • Colorado
    • Denver, Colorado, United States, 80262
      • Univ of Colorado Health Sciences Ctr
  • Florida
    • Miami, Florida, United States, 331361013
      • Univ of Miami School of Medicine
  • Hawaii
    • Honolulu, Hawaii, United States, 96816
      • Univ of Hawaii
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Univ Med School
    • Chicago, Illinois, United States, 60612
      • Rush Presbyterian - Saint Luke's Med Ctr
    • Chicago, Illinois, United States, 60612
      • Cook County Hosp
  • Indiana
    • Indianapolis, Indiana, United States, 462025250
      • Indiana Univ Hosp
    • Indianapolis, Indiana, United States, 46202
      • Methodist Hosp of Indiana / Life Care Clinic
    • Indianapolis, Indiana, United States, 46202
      • Division of Inf Diseases/ Indiana Univ Hosp
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Med Ctr
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess - West Campus
  • Missouri
    • Saint Louis, Missouri, United States, 63112
      • St Louis Regional Hosp / St Louis Regional Med Ctr
  • New York
    • New York, New York, United States, 10021
      • Cornell Univ Med Ctr
    • New York, New York, United States, 10016
      • Bellevue Hosp / New York Univ Med Ctr
    • New York, New York, United States, 10029
      • Mount Sinai Med Ctr
    • New York, New York, United States, 10021
      • Chelsea Ctr
    • New York, New York, United States, 10032
      • Columbia Presbyterian Med Ctr
    • New York, New York, United States, 10021
      • Aaron Diamond AIDS Rsch Ctr / Rockefeller Univ
  • North Carolina
    • Chapel Hill, North Carolina, United States, 275997215
      • Univ of North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Univ Med Ctr
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve Univ
    • Cleveland, Ohio, United States, 441091998
      • MetroHealth Med Ctr
    • Columbus, Ohio, United States, 432101228
      • Ohio State Univ Hosp Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Univ of Pennsylvania at Philadelphia
    • Philadelphia, Pennsylvania, United States, 19104
      • Philadelphia Veterans Administration Med Ctr
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Julio Arroyo
  • Texas
    • Galveston, Texas, United States, 775550435
      • Univ of Texas Galveston
  • Washington
    • Seattle, Washington, United States, 98104
      • Univ of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Jeffrey Jacobson; Study Chair: Gail Skowron; Study Chair: Pablo Tebas

Study record dates

Study Major Dates

• Study Completion (Actual): December 1, 2003

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Actual): October 29, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Anti-HIV Agents; HIV-1; RNA, Viral; Viral Load; Granulocyte-Macrophage Colony-Stimulating Factor; Receptors, Chemokine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Immunologic Factors; Protease Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Indinavir; Sargramostim
• Other Study ID Numbers: A5041; AACTG A5041; 10887 (Registry Identifier: DAIDS ES Registry Number); ACTG A5041 (Other Identifier: ACTG)