Evaluation of Specific Infection-Fighting Cells For Prediction of Immune Response to Anti-HIV and Immune-Boosting Medication

Evaluation of the Relationship Between Immunologic Recovery After Highly Active Antiretroviral Therapy and the Ability to Mobilize CD34+ Stem Cells Following G-CSF Administration

The purpose of this study is to see if the amount of stem cells (cells that can develop into many kinds of cells) in the blood before anti-HIV drugs are taken can predict if the immune system will become stronger after anti-HIV drugs are given and if anti-HIV drugs can restore stem cells.

HIV infection has been shown to cause stem cells not to function well. Granulocyte colony-stimulating factor (G-CSF), which causes stem cells to go from the bone marrow (tissues in the bones where blood cells are formed) into the bloodstream, could possibly help boost immunity after anti-HIV treatment. This study examines the effects of G-CSF in helping the immune system become stronger after beginning anti-HIV treatment.

Study Overview

• Status: Withdrawn
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Lamivudine; Drug: Ritonavir; Drug: Filgrastim; Drug: Abacavir sulfate; Drug: Amprenavir

Detailed Description

In HIV infection, a progressive decline and/or dysfunction of several cell types is seen. It is thought that stem cell dysfunction or destruction may contribute to the hematologic and immunologic perturbations characteristic of HIV infection and may possibly limit the extent of immunologic recovery following HAART. This study proposes to investigate whether stem cell function and reserves are important in determining the extent of immune reconstitution following HAART.

Patients are stratified according to CD4 count. On Day 0, patients receive a 7-day cycle of subcutaneous granulocyte colony-stimulating factor (G-CSF). Blood samples are collected regularly, and on Day 14 patients undergo real-time HIV-1 RNA determinations. On Day 28, or sooner if HIV RNA is at least 1 log above baseline on Day 14, HAART consisting of daily receipt of abacavir, lamivudine, amprenavir, and ritonavir is initiated and continues until Week 76. Patients who achieve viral suppression (below 400 copies/ml of plasma HIV-1 RNA) by Week 26 are eligible to receive a second 7-day cycle of G-CSF at Week 28 and, if viral suppression continues through Week 50, a third cycle of G-CSF at Week 52. Patients are followed every 8 weeks for changes in viral load. Additionally, patients are monitored at regular intervals for surrogate markers of immunologic recovery and, during each cycle of G-CSF, for measurements of stem cell mobilization. Patients may also volunteer for A5085s (Bone Marrow Aspirate Substudy) at participating sites.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80262
      • Univ of Colorado Health Sciences Ctr
  • Florida
    • Miami, Florida, United States, 331361013
      • Univ of Miami School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Univ Med School
    • Chicago, Illinois, United States, 60612
      • Rush Presbyterian - Saint Luke's Med Ctr
  • North Carolina
    • Chapel Hill, North Carolina, United States, 275997215
      • Univ of North Carolina

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.
• Are at least 18 years of age.
• Have HIV levels of at least 1,000 copies/ml within 28 days prior to study entry.
• Have a CD4 cell count of 500 cells/mm3 or less in the 28 days prior to study entry.
• Have not had anti-HIV therapy or have had no more than 2 weeks of prior anti-HIV therapy 90 days prior to study entry.
• Are a good candidate for anti-HIV therapy.
• Agree to abstinence or use a barrier method of birth control during the study and for 12 weeks afterward.

Exclusion Criteria

Patients will not be eligible for this study if they:

• Are pregnant or breast-feeding.
• Have ever had cancer.
• Have used G-CSF or GM-CSF within 180 days prior to study entry.
• Are allergic to E. coli products (such as insulin or human growth hormone).
• Abuse drugs or alcohol.
• Are receiving or have had, within 14 days prior to study entry, treatment for an opportunistic (AIDS-related) infection.
• Have a medical condition that would interfere with the study.

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: Cara Wilson

Study record dates

Study Registration Dates

• First Submitted: December 1, 2000
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Estimate): March 9, 2015
• Last Update Submitted That Met QC Criteria: March 5, 2015
• Last Verified: June 1, 2003

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Lamivudine; Granulocyte Colony-Stimulating Factor; Stem Cells; HIV Protease Inhibitors; Treatment Naive; Ritonavir; VX 478; abacavir; Antigens, CD34
• Additional Relevant MeSH Terms: Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Antitubercular Agents; Antibiotics, Antitubercular; Ritonavir; Lamivudine; Abacavir; Amprenavir
• Other Study ID Numbers: ACTG A5072; AACTG A5072; Substudy ACTG A5085s