Immune Response to a Therapeutic HIV Vaccine Followed by Treatment Interruption in Patients With Acute or Recent HIV Infection

This study has been completed.
Sponsor:
Collaborators:
Acute Infection and Early Disease Research Program
AIDS Clinical Trials Group
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00183261
First received: September 13, 2005
Last updated: June 7, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to determine whether the HIV vaccine MRKAd5 HIV-1 gag/pol/nef followed by treatment interruption can increase immune system function in adults with acute or recent HIV infection who have started taking anti-HIV drugs.


Condition Intervention Phase
HIV Infections
Biological: MRKAd5 HIV-1 gag/pol/nef
Biological: MRKAd5 HIV-1 gag/pol/nef placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Therapeutic Immunization and Treatment Interruption Among Subjects Who Began Potent Antiretroviral Therapy Within 30 Days of Diagnosis of Acute or Recent HIV Infection

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Average of log10 HIV-1 RNA viral load [ Time Frame: At Weeks 58 and 63 ] [ Designated as safety issue: No ]
  • Frequency of Grade 3 or 4 systemic adverse events, the occurrence of a severe or life-threatening injection site adverse event, or death [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Distribution of plasma HIV RNA viral load [ Time Frame: At Weeks 63 and 87 ] [ Designated as safety issue: No ]
  • Proportion of patients with controlled viremia and their respective distribution of plasma HIV RNA viral load [ Time Frame: At Weeks 63 and 87 ] [ Designated as safety issue: No ]
  • Mean viral burden, defined as time-averaged area under the log10 HIV-1 RNA viral load curve [ Time Frame: At Weeks 63 and 87 ] [ Designated as safety issue: No ]
  • HIV DNA levels [ Time Frame: At Weeks 30, 38, 63, and 87 ] [ Designated as safety issue: No ]
  • HIV-1 DNA levels [ Time Frame: At Weeks 30, 38, 46, 50, 63, and 87 ] [ Designated as safety issue: No ]
  • Magnitude and absolute change in CD4 and CD8 counts [ Time Frame: At Weeks 63 and 87 ] [ Designated as safety issue: No ]
  • Percent and absolute change in the number of HIV-1- specific CD8 cells, as measured by interferon (IFN)-gamma Elispot assay and intracellular cytokine staining [ Time Frame: Through Week 30 ] [ Designated as safety issue: No ]
  • Percent and absolute change in the cytokine secretion patterns and the proliferative capacity of HIV-1- specific CD4 and CD8 cells, as measured by multiparameter flow cytometry [ Time Frame: Through Week 30 ] [ Designated as safety issue: No ]
  • Breadth and magnitude of HIV-1- specific CD4 and CD8 cell responses [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Time to reach the specified virologic or immunologic criteria for reinitiating antiretroviral therapy after treatment interruption [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Frequency of Grade 3 or 4 systemic adverse events or the occurrence of a severe or life-threatening injection site adverse event, or HIV-related events, AIDS-defining infections, and death from time of vaccination [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Cell-associated infectivity in latently infected cells [ Time Frame: At Week 63 ] [ Designated as safety issue: No ]
  • Cell-associated infectivity at Week 63 and immunologic responses [ Time Frame: At Weeks 63 and 87 ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: March 2006
Study Completion Date: October 2010
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Participants will receive the MRKAd5 HIV-1 gag/pol/nef vaccine at study entry and on Weeks 4 and 26
Biological: MRKAd5 HIV-1 gag/pol/nef
1.5 x 1010 Ad vg/mL, 1.0 mL administered intramuscularly
Placebo Comparator: 2
Participants will receive the MRKAd5 HIV-1 gag/pol/nef vaccine placebo at study entry and on Weeks 4 and 26
Biological: MRKAd5 HIV-1 gag/pol/nef placebo
1.0 mL administered intramuscularly

Detailed Description:

While the advent of highly active antiretroviral therapy (HAART) has contributed to the increasing control of HIV infection and viral replication, ultimate control of HIV infection will require the development of effective HIV-specific immunity in HIV infected individuals. Therapeutic vaccination within the earliest weeks following acute or recent HIV infection may increase the immune system's response to HIV. This study will determine whether MRKAd5 HIV-1 gag/pol/nef vaccine followed by treatment interruption can maintain viral suppression in patients with acute or recent HIV infection.

The interventional part of the study will last 102 weeks. Participants will be randomly assigned to receive either MRKAd5 HIV-1 gag/pol/nef or placebo vaccine at baseline and Weeks 4 and 26. Participants must remain on HAART from study entry until Week 38. Participants whose HIV viral load rebounds two times or more above 500 copies/ml by Weeks 39 to 41 will not enter Step 2 of the study. Participants whose viral load drops to 500 copies/ml or less by Weeks 39 to 41 will enter Step 2, where they will discontinue HAART for 24 weeks. Participants in Step 2 will have plasma HIV viral loads measured every 2 weeks for the first 4 weeks and weekly for the next 3 weeks. Study participants will continue in Step 2 until they experience virologic and immunologic failure or they need to restart HAART for another reason; they will then enter Step 3, where they will reinitiate HAART. Step 3 participants will continue on HAART until Week 102. A long-term safety follow-up period will occur from Weeks 103 to 240.

Timing of the study visits will be determined by which steps a participant enters. A physical exam and blood and urine collection will occur at most study visits throughout the study until Week 102. Follow-up phone calls to study participants will occur every 6 months from Week 102 until Week 240 to collect long-term safety data, including clinical status, CD4 count, and medication history. During the long-term safety follow-up, participants will also have study visits every 6 months. Visits will include medical and medication history.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Initiated HAART within 30 days of an acute or recent HIV-1 infection diagnosis. More information on this criterion can be found in the protocol.
  • Initiated HAART within 30 days of documented acute or recent HIV-1 infection without interruption for more than 7 days
  • Sustained viral suppression, defined as a viral load of 500 copies/mL or less 12 months prior to baseline with an undetectable HIV-1 RNA viral load between 60 to 7 days prior to baseline
  • CD4 count of 450 cells/mm3 or more OR 35% or more between 60 to 14 days prior to baseline
  • Ad5 neutralizing antibody titer of 200 or less at screening
  • Willing to follow all study procedures and schedules
  • Willing to interrupt HAART for at least 24 weeks following completion of the vaccination stage
  • Negative for hepatitis B surface antigen (HBsAg) at screening
  • Willing to use acceptable forms of contraception
  • Infected with HIV-1 subtype B, if this information is available

Exclusion Criteria:

  • Virologic relapse, defined as 2 consecutive measurements of viral load of 500 copies/mL or more at least 7 days apart within 12 months of baseline visit
  • Received more than 7 days of continuous HAART other than that received within 16 days of acute or recent HIV-1 infection. Participants who received HAART as part of post-exposure prophylaxis (PEP) more than 6 months prior to the start of initial HAART may be eligible, provided that they did not acquire HIV-1 infection from the event that required PEP.
  • History of anaphylaxis or allergy to vaccine components, including Tris buffer, magnesium chloride, and polysorbate 80 (Tween)
  • History of clinically significant heart, lung, kidney, liver, pancreatic, gastrointestinal, or neurological disease that, in the opinion of the study investigator, may interfere with the study
  • Contraindication to intramuscular (IM) injection, such as anticoagulant therapy or thrombocytopenia
  • Receipt of any immune globulin or blood products within 3 months prior to baseline
  • Receipt of any live vaccine within 30 days prior to baseline or any inactivated vaccine within 14 days prior to baseline
  • Previous receipt of any HIV vaccine. Participants that were documented to have received only placebo are not excluded.
  • History of any AIDS-defining illness. If a participant's sole AIDS-defining illness is Kaposi's sarcoma limited to the skin and is not anticipated to require systemic chemotherapy, that participant is not excluded.
  • Currently receiving drugs or biologics not approved by the Food and Drug Administration (FDA) other than investigational HIV medications
  • Current or past participation in other studies that might alter the participant's response to the study vaccination
  • Use of any immunomodulatory agents, including but not limited to interleukin-2 (IL-2), granulocyte/macrophage-colony stimulating factor (GM-CSF), and systemic corticosteroids, within 30 days prior to baseline
  • Active alcohol or substance use that, in the investigator's opinion, may interfere with the study
  • Any other criteria or condition that, in the investigator's opinion, may interfere with the study
  • Unwilling or unable to contribute to the planned peripheral blood mononuclear cell (PBMC) blood collection
  • Pregnancy or breastfeeding
  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: NCT00183261

Locations
United States, California
Ucsd Aiedrp
San Diego, California, United States, 92103
Ucsf Aiedrp
San Francisco, California, United States, 94110
LA Biomedical Research Institute at Harbor-UCLA AIEDRP
Torrance, California, United States
United States, Colorado
Univ. of Colorado Health Sciences Ctr. AIEDRP
Denver, Colorado, United States, 80220
United States, Massachusetts
Fenway Community Health Ctr. CRS
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington U CRS
St. Louis, Missouri, United States, 63110
United States, New York
Aaron Diamond AIDS Research Ctr. AIEDRP
New York, New York, United States, 10016
Beth Israel Med. Ctr., ACTU
New York, New York, United States, 10003
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 27514
UNC, Chapel Hill AIEDRP
Chapel Hill, North Carolina, United States, 27599
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, United States, 27710
Dumc Aiedrp
Durham, North Carolina, United States
United States, Rhode Island
The Miriam Hosp. ACTG CRS
Providence, Rhode Island, United States, 02906
American Samoa
407 Doctors CRS
Surry Hills, American Samoa, 2010
Australia, New South Wales
Holdsworth House Medical Practice CRS
Darlinghurst, New South Wales, Australia, 2010
AIDS Research Initiative, Darlinghurst CRS
Darlinghurst, New South Wales, Australia
Taylor Square Private Clinic CRS
Darlinghurst, New South Wales, Australia, 2010
St. Vincent's Hospital CRS
Darlinghurst, New South Wales, Australia, 2010
Australia
Taylor Square Private Clinic (Australia) AIEDRP
Sydney, Australia, 2010
407 Doctors (Australia) AIEDRP
Sydney, Australia, 2010
AIDS Research Initiative (Australia) AIEDRP
Sydney, Australia, 2010
Holdsworth House Gen. Practice (Australia) AIEDRP
Sydney, Australia
St. Vincent's Hosp. (Australia) AIEDRP
Sydney, Australia, 2010
Sponsors and Collaborators
Acute Infection and Early Disease Research Program
AIDS Clinical Trials Group
Investigators
Study Chair: Susan Little, MD University of California, San Diego AIDS Vaccine Research Center
Study Chair: Douglas D. Richman, MD Departments of Pathology and Medicine, University of California, San Diego
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00183261     History of Changes
Other Study ID Numbers: AIN504/A5218, 10025, AIN504/ACTG A5218, AIN504-A5218
Study First Received: September 13, 2005
Last Updated: June 7, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Interruption
HIV Therapeutic Vaccine
Acute Infection
Acute Retroviral Syndrome

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 24, 2014