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

NCT ID: NCT00183261

Last Updated: 2021-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-03-31

Study Completion Date

2010-10-31

Brief Summary

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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

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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.

Conditions

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HIV Infections

Keywords

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Treatment Interruption HIV Therapeutic Vaccine Acute Infection Acute Retroviral Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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1

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

Group Type EXPERIMENTAL

MRKAd5 HIV-1 gag/pol/nef

Intervention Type BIOLOGICAL

1.5 x 1010 Ad vg/mL, 1.0 mL administered intramuscularly

2

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

Group Type PLACEBO_COMPARATOR

MRKAd5 HIV-1 gag/pol/nef placebo

Intervention Type BIOLOGICAL

1.0 mL administered intramuscularly

Interventions

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MRKAd5 HIV-1 gag/pol/nef

1.5 x 1010 Ad vg/mL, 1.0 mL administered intramuscularly

Intervention Type BIOLOGICAL

MRKAd5 HIV-1 gag/pol/nef placebo

1.0 mL administered intramuscularly

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Acute Infection and Early Disease Research Program

NETWORK

Sponsor Role collaborator

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Susan Little, MD

Role: STUDY_CHAIR

University of California, San Diego AIDS Vaccine Research Center

Douglas D. Richman, MD

Role: STUDY_CHAIR

Departments of Pathology and Medicine, University of California, San Diego

Locations

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Ucsd Aiedrp

San Diego, California, United States

Site Status

Ucsf Aiedrp

San Francisco, California, United States

Site Status

LA Biomedical Research Institute at Harbor-UCLA AIEDRP

Torrance, California, United States

Site Status

Univ. of Colorado Health Sciences Ctr. AIEDRP

Denver, Colorado, United States

Site Status

Fenway Community Health Ctr. CRS

Boston, Massachusetts, United States

Site Status

Washington U CRS

St Louis, Missouri, United States

Site Status

Beth Israel Med. Ctr., ACTU

New York, New York, United States

Site Status

Aaron Diamond AIDS Research Ctr. AIEDRP

New York, New York, United States

Site Status

Unc Aids Crs

Chapel Hill, North Carolina, United States

Site Status

UNC, Chapel Hill AIEDRP

Chapel Hill, North Carolina, United States

Site Status

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, United States

Site Status

Dumc Aiedrp

Durham, North Carolina, United States

Site Status

The Miriam Hosp. ACTG CRS

Providence, Rhode Island, United States

Site Status

407 Doctors CRS

Surry Hills, New South Wales, American Samoa

Site Status

Holdsworth House Medical Practice CRS

Darlinghurst, New South Wales, Australia

Site Status

St. Vincent's Hospital CRS

Darlinghurst, New South Wales, Australia

Site Status

Taylor Square Private Clinic CRS

Darlinghurst, New South Wales, Australia

Site Status

AIDS Research Initiative, Darlinghurst CRS

Darlinghurst, New South Wales, Australia

Site Status

407 Doctors (Australia) AIEDRP

Sydney, , Australia

Site Status

AIDS Research Initiative (Australia) AIEDRP

Sydney, , Australia

Site Status

St. Vincent's Hosp. (Australia) AIEDRP

Sydney, , Australia

Site Status

Taylor Square Private Clinic (Australia) AIEDRP

Sydney, , Australia

Site Status

Holdsworth House Gen. Practice (Australia) AIEDRP

Sydney, , Australia

Site Status

Countries

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United States American Samoa Australia

References

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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.

Reference Type BACKGROUND
PMID: 12195350 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12559781 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10950770 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11029005 (View on PubMed)

Other Identifiers

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10025

Identifier Type: REGISTRY

Identifier Source: secondary_id

AIN504/ACTG A5218

Identifier Type: -

Identifier Source: secondary_id

AIN504-A5218

Identifier Type: -

Identifier Source: secondary_id

AIN504/A5218

Identifier Type: -

Identifier Source: org_study_id