Effectiveness of and Immune Response to HIV Vaccination Followed by Treatment Interruption in HIV Infected Patients

A Phase II Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Antiretroviral Effect of Immunization With the MRK Ad5 HIV-1 Gag Vaccine in HIV-1 Infected Individuals Who Interrupt Antiretroviral Therapy

HIV vaccines may help the immune systems of HIV infected patients better control the virus. The goal of this study is to determine whether patients on anti-HIV medications can stop taking those medications if they receive an HIV vaccine. While taking anti-HIV medications, participants will receive either an HIV vaccine or a placebo. Participants will then stop taking their anti-HIV medications and the study will compare the viral loads of participants who received the vaccine with the viral loads of participants who received the placebo.

Primary study hypotheses: 1)The Week 12 and Week 16 post-ART interruption geometric mean HIV-1 RNA levels will be lower among participants who had received MRK Ad5 vaccine prior to ART interruption than among participants who received placebo; 2) the time averaged area under the curve of the log10 HIV-1 RNA copies/ml versus day function in the 16 week post-ART interruption step will be lower among participants who received the MRK Ad5 vaccine prior to ART interruption than among participants who receive placebo.

Study Overview

Status

Completed

Conditions

Detailed Description

Antiretroviral therapy (ART) has a significant impact on HIV disease; however, HIV cannot be cured with current drug regimens. While the majority of patients initially benefit from ART, drug regimens subsequently fail for many patients due to drug resistance, poor adherence, or toxicity. If given while HIV replication is kept in check by ART, an HIV vaccine may be able to generate an effective long-term immune response capable of controlling the virus, even if ART is discontinued.

The MRK Ad5 HIV-1 gag vaccine uses a replication-defective adenovirus vector and has been found safe in clinical trials of both HIV infected and HIV uninfected adults. This study will evaluate the ability of immunization with the MRK Ad5 HIV-1 gag vaccine to control HIV replication in individuals undergoing treatment interruption. The study will enroll individuals whose HIV replication has been successfully suppressed with ART for at least 2 years.

Participants in this study will be randomly assigned to receive either vaccine or placebo. Both vaccine and placebo will be injected into the upper arm muscle. Participants will take their antiretroviral medications during the first 3 months of the study. Injections will be given on Day 1, Week 4, and Week 26. A study nurse will call participants 1 or 2 days after each injection and participants will be asked to fill out a card with any reactions they have to the injections. About 3 months after the third injection, participants will stop taking their antiretroviral medications for 4 months. Participants will have study visits every 2 to 3 weeks while off medication. After 4 months, participants will have the option of restarting antiretroviral medications or continuing without medication. Participants will then have study visits every 2 months for 8 months. Study visits will include physical exams and blood collection.

All participants will continue to see their primary care provider for HIV treatment and will be restarted on antiretroviral medications if clinically indicated. Participants or their primary care provider will be contacted by phone for updates every 6 months for an additional 3.5 years.

Study Type

Interventional

Enrollment (Actual)

114

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • San Juan, Puerto Rico, 00935
        • Puerto Rico-AIDS CRS
    • California
      • Los Angeles, California, United States, 90035
        • UCLA CARE Center CRS
      • Palo Alto, California, United States, 94304-5350
        • Stanford CRS
      • Sacramento, California, United States, 95817
        • Univ. of California Davis Med. Ctr., ACTU
      • San Diego, California, United States, 92103
        • Ucsd, Avrc Crs
      • San Francisco, California, United States, 94110
        • Ucsf Aids Crs
    • Florida
      • Miami, Florida, United States, 33136
        • Univ. of Miami AIDS CRS
    • Hawaii
      • Honolulu, Hawaii, United States, 96816
        • Univ. of Hawaii at Manoa, Leahi Hosp.
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush Univ. Med. Ctr. ACTG CRS
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5250
        • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • IHV Baltimore Treatment CRS
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital ACTG CRS
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Med. Ctr., ACTG CRS
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota, ACTU
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington U CRS
    • New York
      • New York, New York, United States, 10003
        • Beth Israel Med. Ctr., ACTU
      • New York, New York, United States, 10016
        • NY Univ. HIV/AIDS CRS
      • New York, New York, United States, 10021
        • Cornell CRS
      • Rochester, New York, United States, 14642
        • Univ. of Rochester ACTG CRS
      • Rochester, New York, United States, 14607
        • AIDS Care CRS
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • Unc Aids Crs
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case CRS
      • Cleveland, Ohio, United States, 44109
        • MetroHealth CRS
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Pitt CRS
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • The Miriam Hosp. ACTG CRS
    • Texas
      • Galveston, Texas, United States
        • Univ. of Texas Medical Branch, ACTU
    • Washington
      • Seattle, Washington, United States, 98104
        • University of Washington AIDS CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

  • HIV infected
  • On a stable antiretroviral medication regimen (no changes to treatment within 4 weeks of study entry)
  • Viral load less than 50 copies/ml
  • Viral suppression for 2 years prior to study entry (documented viral loads less than 500 copies/ml)
  • CD4 count of 500 cells/mm3 or greater
  • Ad5 neutralizing antibody less than 200 units at screening
  • Willing to stop antiretroviral medications for at least 16 weeks post-vaccination
  • Hepatitis B surface antigen negative
  • Weight more than 110 lbs
  • Willing to use acceptable methods of contraception

Exclusion Criteria

  • Two consecutive viral loads of 500 copies/ml or greater at least 14 days apart during the 24 months prior to study entry
  • Two consecutive CD4 counts less than 200 cells/mm3 before starting antiretroviral medications
  • History of anaphylaxis
  • Allergy to vaccine components
  • History of cardiac, pulmonary, gastrointestinal, hepatic, renal, pancreatic, or neurologic disease which, in the opinion of the study official, will compromise study participation
  • Pregnancy or breastfeeding
  • Contraindication to intramuscular injection, such as anticoagulant therapy or thrombocytopenia
  • Immune globulin or blood products within 3 months prior to study entry
  • Live vaccine within 30 days prior to study entry
  • Inactivated vaccine within 14 days prior to study entry
  • Previous HIV vaccine
  • History of an AIDS-defining illness. Patients with a history of Kaposi's sarcoma limited to the skin may participate.
  • Currently taking drugs or other substances not approved by the FDA. Patients may be on antiretroviral agents not yet approved by the FDA as part of a clinical trial or through an expanded access program.
  • Immunomodulatory agents (interferon, IL-2, GM-CSF, systemic corticosteroids, etc.) within 30 days prior to study entry
  • Active alcohol or substance abuse which may interfere with the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Participants in the experimental arm will receive the MRK Ad5 HIV-1 gag vaccine on Day 1, Week 4 and Week 26. Participants will take their antiretroviral medications during the first 3 months of the study.
MRK Ad5 HIV-1 gag vaccine injected into the upper arm muscle.
Placebo Comparator: 2
Participants in Arm 2 will receive a placebo vaccine on Day 1, Week 4 and Week 26. Participants will take their antiretroviral medications during the first 3 months of the study.
MRK Ad5 HIV-1 gag placebo vaccine injected into the upper arm muscle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Analytical treatment interruption (ATI) HIV-1 RNA set-point
Time Frame: Throughout study
Throughout study
ATI log10 HIV-1 RNA copies/ml at all scheduled evaluations during Step II (ATI)
Time Frame: Throughout Step 2
Throughout Step 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Robert T. Schooley, MD, University of Colorado, Denver

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2004

Primary Completion (Actual)

September 1, 2007

Study Completion (Actual)

May 1, 2011

Study Registration Dates

First Submitted

March 23, 2004

First Submitted That Met QC Criteria

March 24, 2004

First Posted (Estimate)

March 25, 2004

Study Record Updates

Last Update Posted (Actual)

November 9, 2021

Last Update Submitted That Met QC Criteria

November 4, 2021

Last Verified

July 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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