Effectiveness of and Immune Response to HIV Vaccination Followed by Treatment Interruption in HIV Infected Patients - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00080106

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Biological: MRK Ad5 HIV-1 gag vaccine Other: Vaccine placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: AIDS

U.S. FDA Resources

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

Primary Outcome Measures:

Analytical treatment interruption (ATI) HIV-1 RNA set-point [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
ATI log10 HIV-1 RNA copies/ml at all scheduled evaluations during Step II (ATI) [ Time Frame: Throughout Step 2 ] [ Designated as safety issue: No ]

Estimated Enrollment:	120
Study Start Date:	June 2004
Primary Completion Date:	June 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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.	Biological: MRK Ad5 HIV-1 gag vaccine MRK Ad5 HIV-1 gag vaccine injected into the upper arm muscle.
2: Placebo Comparator 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.	Other: Vaccine placebo MRK Ad5 HIV-1 gag placebo vaccine injected into the upper arm muscle.

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.

Eligibility

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

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00080106

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Locations

United States, California
Stanford University
Stanford, California, United States, 94305-5107
San Mateo County AIDS Program
Stanford, California, United States, 94305-5107
Santa Clara Valley Medical Center
Stanford, California, United States, 94305-5107
Willow Clinic
Stanford, California, United States, 94305-5107
UCLA School of Medicine
Los Angeles, California, United States, 90095-1793
San Francisco General Hospital
San Francisco, California, United States, 94110
University of California, San Diego Antiviral Rese
San Diego, California, United States, 92103
University of California, Davis Medical Center
Sacremento, California, United States, 95814
United States, Colorado
Univ. of Colorado Health Sciences Center, Denver
Denver, Colorado, United States, 80262-3706
United States, Florida
University of Miami
Miami, Florida, United States, 33136-1013
United States, Hawaii
University of Hawaii
Honolulu, Hawaii, United States, 96816-2396
United States, Illinois
Rush-Presbyterian/St. Lukes (Chicago)
Chicago, Illinois, United States, 60612-3806
United States, Indiana
Indiana University Hospital
Indianapolis, Indiana, United States, 46202-5250
Methodist Hospital of Indiana
Indianapolis, Indiana, United States, 46202-5250
United States, Maryland
University of Maryland, Institute of Human Virology
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Harvard (Massachusetts General Hospital)
Boston, Massachusetts, United States, 02114
Brigham and Womens Hospital
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States, 02215
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455-0392
United States, Missouri
Washington University (St. Louis)
St. Louis, Missouri, United States, 63108-2138
United States, New York
Community Health Network, Inc.
Rochester, New York, United States, 14642-0001
Beth Israel Medical Center
New York, New York, United States, 10003
The Cornell Clinical Trials Unit
New York, New York, United States, 10021
Chelsea Clinic
New York, New York, United States, 10011
University of Rochester Medical Center
Rochester, New York, United States, 14642-0001
NYU/Bellevue
New York, New York, United States, 10016-6481
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27514
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106-5083
Cleveland Clinic
Cleveland, Ohio, United States, 44106
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109-1998
Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213-2582
United States, Rhode Island
The Miriam Hospital
Providence, Rhode Island, United States, 02906
United States, Texas
University of Texas, Southwestern Medical Center
Dallas, Texas, United States, 75235-9173
University of Texas, Galveston
Galveston, Texas, United States, 77555-0435
United States, Washington
University of Washington (Seattle)
Seattle, Washington, United States, 98104
Puerto Rico
University of Puerto Rico
San Juan, Puerto Rico, 00936-5067

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:

Robert T. Schooley, MD

University of Colorado at Denver and Health Sciences Center

More Information

Additional Information:

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

Publications:

Shiver JW, Fu TM, Chen L, Casimiro DR, Davies ME, Evans RK, Zhang ZQ, Simon AJ, Trigona WL, Dubey SA, Huang L, Harris VA, Long RS, Liang X, Handt L, Schleif WA, Zhu L, Freed DC, Persaud NV, Guan L, Punt KS, Tang A, Chen M, Wilson KA, Collins KB, Heidecker GJ, Fernandez VR, Perry HC, Joyce JG, Grimm KM, Cook JC, Keller PM, Kresock DS, Mach H, Troutman RD, Isopi LA, Williams DM, Xu Z, Bohannon KE, Volkin DB, Montefiori DC, Miura A, Krivulka GR, Lifton MA, Kuroda MJ, Schmitz JE, Letvin NL, Caulfield MJ, Bett AJ, Youil R, Kaslow DC, Emini EA. Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature. 2002 Jan 17;415(6869):331-5.

Ortiz GM, Wellons M, Brancato J, Vo HT, Zinn RL, Clarkson DE, Van Loon K, Bonhoeffer S, Miralles GD, Montefiori D, Bartlett JA, Nixon DF. Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects. Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13288-93. Epub 2001 Oct 30.

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.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	ACTG A5197
Study First Received:	March 23, 2004
Last Updated:	November 10, 2009
ClinicalTrials.gov Identifier:	NCT00080106 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

HIV Therapeutic Vaccine
Treatment Experienced
Treatment Interruption
Adenovirus Vector

Additional relevant MeSH terms:

Virus Diseases
Sexually Transmitted Diseases, Viral
RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
HIV Infections

Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Infection
Retroviridae Infections
Immunologic Deficiency Syndromes

ClinicalTrials.gov processed this record on November 27, 2009