Clinical trial NCT00000850: The Effectiveness of GM-CSF in HIV-Positive Patients Who Are Also Receiving Anti-HIV Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: HIV-1
Granulocyte-Macrophage Colony-Stimulating Factor
RNA, Viral
Anti-HIV Agents
Viral Load
Receptors, Chemokine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Kaiser Permanente LAMC
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Ctr
state: California
city: Menlo Park
country: United States
facility: Willow Clinic
state: California
city: San Diego
country: United States
facility: Univ of California / San Diego Treatment Ctr
state: California
city: San Francisco
country: United States
facility: San Francisco Gen Hosp
state: California
city: San Jose
country: United States
facility: Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
state: California
city: San Rafael
country: United States
facility: Marin County Specialty Clinic
state: California
city: Stanford
country: United States
facility: San Mateo AIDS Program / Stanford Univ
state: California
city: Stanford
country: United States
facility: Stanford Univ Med Ctr
state: California
city: Torrance
country: United States
facility: Harbor UCLA Med Ctr
state: California
city: Denver
country: United States
facility: Univ of Colorado Health Sciences Ctr
state: Colorado
city: Miami
country: United States
facility: Univ of Miami School of Medicine
state: Florida
city: Honolulu
country: United States
facility: Univ of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Univ Med School
state: Illinois
city: Chicago
country: United States
facility: Cook County Hosp
state: Illinois
city: Chicago
country: United States
facility: Rush Presbyterian - Saint Luke's Med Ctr
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ Hosp
state: Indiana
city: Indianapolis
country: United States
facility: Division of Inf Diseases/ Indiana Univ Hosp
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hosp of Indiana / Life Care Clinic
state: Indiana
city: Boston
country: United States
facility: Boston Med Ctr
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess - West Campus
state: Massachusetts
city: Saint Louis
country: United States
facility: St Louis Regional Hosp / St Louis Regional Med Ctr
state: Missouri
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: Aaron Diamond AIDS Rsch Ctr / Rockefeller Univ
state: New York
city: New York
country: United States
facility: Chelsea Ctr
state: New York
city: New York
country: United States
facility: Cornell Univ Med Ctr
state: New York
city: New York
country: United States
facility: Mount Sinai Med Ctr
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Med Ctr
state: New York
city: Chapel Hill
country: United States
facility: Univ of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke Univ Med Ctr
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve Univ
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Med Ctr
state: Ohio
city: Columbus
country: United States
facility: Ohio State Univ Hosp Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Philadelphia Veterans Administration Med Ctr
state: Pennsylvania
city: Philadelphia
country: United States
facility: Univ of Pennsylvania at Philadelphia
state: Pennsylvania
city: West Columbia
country: United States
facility: Julio Arroyo
state: South Carolina
city: Galveston
country: United States
facility: Univ of Texas Galveston
state: Texas
city: Seattle
country: United States
facility: Univ of Washington
state: Washington
Study officials:
name: Jeffrey Jacobson
role: STUDY_CHAIR
name: Gail Skowron
role: STUDY_CHAIR
name: Pablo Tebas
role: STUDY_CHAIR
name: Hernan Valdez
role: STUDY_CHAIR
References: