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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MRKAd5 HIV-1 gag/pol/nef
MRKAd5 HIV-1 gag/pol/nef placebo
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Treatment Interruption, HIV Therapeutic Vaccine, Acute Infection, Acute Retroviral Syndrome

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Ucsd Aiedrp
  • Ucsf Aiedrp
  • LA Biomedical Research Institute at Harbor-UCLA AIEDRP
  • Univ. of Colorado Health Sciences Ctr. AIEDRP
  • Fenway Community Health Ctr. CRS
  • Washington U CRS
  • Beth Israel Med. Ctr., ACTU
  • Aaron Diamond AIDS Research Ctr. AIEDRP
  • Unc Aids Crs
  • UNC, Chapel Hill AIEDRP
  • Duke Univ. Med. Ctr. Adult CRS
  • Dumc Aiedrp
  • The Miriam Hosp. ACTG CRS
  • 407 Doctors CRS
  • Holdsworth House Medical Practice CRS
  • St. Vincent's Hospital CRS
  • Taylor Square Private Clinic CRS
  • AIDS Research Initiative, Darlinghurst CRS
  • 407 Doctors (Australia) AIEDRP
  • AIDS Research Initiative (Australia) AIEDRP
  • St. Vincent's Hosp. (Australia) AIEDRP
  • Taylor Square Private Clinic (Australia) AIEDRP
  • Holdsworth House Gen. Practice (Australia) AIEDRP

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1

2

Arm Description

Participants will receive the MRKAd5 HIV-1 gag/pol/nef vaccine at study entry and on Weeks 4 and 26

Participants will receive the MRKAd5 HIV-1 gag/pol/nef vaccine placebo at study entry and on Weeks 4 and 26

Outcomes

Primary Outcome Measures

Average of log10 HIV-1 RNA viral load
Frequency of Grade 3 or 4 systemic adverse events, the occurrence of a severe or life-threatening injection site adverse event, or death

Secondary Outcome Measures

Distribution of plasma HIV RNA viral load
Proportion of patients with controlled viremia and their respective distribution of plasma HIV RNA viral load
Mean viral burden, defined as time-averaged area under the log10 HIV-1 RNA viral load curve
HIV DNA levels
HIV-1 DNA levels
Magnitude and absolute change in CD4 and CD8 counts
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
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
Breadth and magnitude of HIV-1- specific CD4 and CD8 cell responses
Time to reach the specified virologic or immunologic criteria for reinitiating antiretroviral therapy after treatment interruption
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
Cell-associated infectivity in latently infected cells
Cell-associated infectivity at Week 63 and immunologic responses

Full Information

First Posted
September 13, 2005
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Acute Infection and Early Disease Research Program, AIDS Clinical Trials Group
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1. Study Identification

Unique Protocol Identification Number
NCT00183261
Brief Title
Immune Response to a Therapeutic HIV Vaccine Followed by Treatment Interruption in Patients With Acute or Recent HIV Infection
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
March 2006 (undefined)
Primary Completion Date
August 2007 (Actual)
Study Completion Date
October 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Acute Infection and Early Disease Research Program, AIDS Clinical Trials Group

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Treatment Interruption, HIV Therapeutic Vaccine, Acute Infection, Acute Retroviral Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Participants will receive the MRKAd5 HIV-1 gag/pol/nef vaccine at study entry and on Weeks 4 and 26
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Participants will receive the MRKAd5 HIV-1 gag/pol/nef vaccine placebo at study entry and on Weeks 4 and 26
Intervention Type
Biological
Intervention Name(s)
MRKAd5 HIV-1 gag/pol/nef
Intervention Description
1.5 x 1010 Ad vg/mL, 1.0 mL administered intramuscularly
Intervention Type
Biological
Intervention Name(s)
MRKAd5 HIV-1 gag/pol/nef placebo
Intervention Description
1.0 mL administered intramuscularly
Primary Outcome Measure Information:
Title
Average of log10 HIV-1 RNA viral load
Time Frame
At Weeks 58 and 63
Title
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
Secondary Outcome Measure Information:
Title
Distribution of plasma HIV RNA viral load
Time Frame
At Weeks 63 and 87
Title
Proportion of patients with controlled viremia and their respective distribution of plasma HIV RNA viral load
Time Frame
At Weeks 63 and 87
Title
Mean viral burden, defined as time-averaged area under the log10 HIV-1 RNA viral load curve
Time Frame
At Weeks 63 and 87
Title
HIV DNA levels
Time Frame
At Weeks 30, 38, 63, and 87
Title
HIV-1 DNA levels
Time Frame
At Weeks 30, 38, 46, 50, 63, and 87
Title
Magnitude and absolute change in CD4 and CD8 counts
Time Frame
At Weeks 63 and 87
Title
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
Title
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
Title
Breadth and magnitude of HIV-1- specific CD4 and CD8 cell responses
Time Frame
Throughout study
Title
Time to reach the specified virologic or immunologic criteria for reinitiating antiretroviral therapy after treatment interruption
Time Frame
Throughout study
Title
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
Title
Cell-associated infectivity in latently infected cells
Time Frame
At Week 63
Title
Cell-associated infectivity at Week 63 and immunologic responses
Time Frame
At Weeks 63 and 87

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan Little, MD
Organizational Affiliation
University of California, San Diego AIDS Vaccine Research Center
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Douglas D. Richman, MD
Organizational Affiliation
Departments of Pathology and Medicine, University of California, San Diego
Official's Role
Study Chair
Facility Information:
Facility Name
Ucsd Aiedrp
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Ucsf Aiedrp
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
LA Biomedical Research Institute at Harbor-UCLA AIEDRP
City
Torrance
State/Province
California
Country
United States
Facility Name
Univ. of Colorado Health Sciences Ctr. AIEDRP
City
Denver
State/Province
Colorado
ZIP/Postal Code
80220
Country
United States
Facility Name
Fenway Community Health Ctr. CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Washington U CRS
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Beth Israel Med. Ctr., ACTU
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Aaron Diamond AIDS Research Ctr. AIEDRP
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Unc Aids Crs
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
UNC, Chapel Hill AIEDRP
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Duke Univ. Med. Ctr. Adult CRS
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Dumc Aiedrp
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
The Miriam Hosp. ACTG CRS
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
Facility Name
407 Doctors CRS
City
Surry Hills
ZIP/Postal Code
2010
Country
American Samoa
Facility Name
Holdsworth House Medical Practice CRS
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
St. Vincent's Hospital CRS
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
Taylor Square Private Clinic CRS
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
AIDS Research Initiative, Darlinghurst CRS
City
Darlinghurst
State/Province
New South Wales
Country
Australia
Facility Name
407 Doctors (Australia) AIEDRP
City
Sydney
ZIP/Postal Code
2010
Country
Australia
Facility Name
AIDS Research Initiative (Australia) AIEDRP
City
Sydney
ZIP/Postal Code
2010
Country
Australia
Facility Name
St. Vincent's Hosp. (Australia) AIEDRP
City
Sydney
ZIP/Postal Code
2010
Country
Australia
Facility Name
Taylor Square Private Clinic (Australia) AIEDRP
City
Sydney
ZIP/Postal Code
2010
Country
Australia
Facility Name
Holdsworth House Gen. Practice (Australia) AIEDRP
City
Sydney
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
12195350
Citation
Markowitz M, Jin X, Hurley A, Simon V, Ramratnam B, Louie M, Deschenes GR, Ramanathan M Jr, Barsoum S, Vanderhoeven J, He T, Chung C, Murray J, Perelson AS, Zhang L, Ho DD. Discontinuation of antiretroviral therapy commenced early during the course of human immunodeficiency virus type 1 infection, with or without adjunctive vaccination. J Infect Dis. 2002 Sep 1;186(5):634-43. doi: 10.1086/342559. Epub 2002 Aug 9.
Results Reference
background
PubMed Identifier
12559781
Citation
Moss RB, Brandt C, Giermakowska WK, Savary JR, Theofan G, Zanetti M, Carlo DJ, Wallace MR. HIV-specific immunity during structured antiviral drug treatment interruption. Vaccine. 2003 Mar 7;21(11-12):1066-71. doi: 10.1016/s0264-410x(02)00610-2.
Results Reference
background
PubMed Identifier
10950770
Citation
Papasavvas E, Ortiz GM, Gross R, Sun J, Moore EC, Heymann JJ, Moonis M, Sandberg JK, Drohan LA, Gallagher B, Shull J, Nixon DF, Kostman JR, Montaner LJ. Enhancement of human immunodeficiency virus type 1-specific CD4 and CD8 T cell responses in chronically infected persons after temporary treatment interruption. J Infect Dis. 2000 Sep;182(3):766-75. doi: 10.1086/315748. Epub 2000 Aug 17.
Results Reference
background
PubMed Identifier
11029005
Citation
Rosenberg ES, Altfeld M, Poon SH, Phillips MN, Wilkes BM, Eldridge RL, Robbins GK, D'Aquila RT, Goulder PJ, Walker BD. Immune control of HIV-1 after early treatment of acute infection. Nature. 2000 Sep 28;407(6803):523-6. doi: 10.1038/35035103.
Results Reference
background

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

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