Clinical trial NCT00080106: Effectiveness of and Immune Response to HIV Vaccination Followed by Treatment Interruption in HIV Infected Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: HIV Therapeutic Vaccine
Treatment Experienced
Treatment Interruption
Adenovirus Vector
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2004-03-25
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Analytical treatment interruption (ATI) HIV-1 RNA set-point
timeFrame: Throughout study
measure: ATI log10 HIV-1 RNA copies/ml at all scheduled evaluations during Step II (ATI)
timeFrame: Throughout Step 2
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: Palo Alto
country: United States
facility: Stanford CRS
state: California
city: Sacramento
country: United States
facility: Univ. of California Davis Med. Ctr., ACTU
state: California
city: San Diego
country: United States
facility: Ucsd, Avrc Crs
state: California
city: San Francisco
country: United States
facility: Ucsf Aids Crs
state: California
city: Miami
country: United States
facility: Univ. of Miami AIDS CRS
state: Florida
city: Honolulu
country: United States
facility: Univ. of Hawaii at Manoa, Leahi Hosp.
state: Hawaii
city: Chicago
country: United States
facility: Rush Univ. Med. Ctr. ACTG CRS
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ. School of Medicine, Infectious Disease Research Clinic
state: Indiana
city: Baltimore
country: United States
facility: IHV Baltimore Treatment CRS
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital ACTG CRS
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Med. Ctr., ACTG CRS
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota, ACTU
state: Minnesota
city: Saint Louis
country: United States
facility: Washington U CRS
state: Missouri
city: New York
country: United States
facility: Beth Israel Med. Ctr., ACTU
state: New York
city: New York
country: United States
facility: NY Univ. HIV/AIDS CRS
state: New York
city: New York
country: United States
facility: Cornell CRS
state: New York
city: Rochester
country: United States
facility: AIDS Care CRS
state: New York
city: Rochester
country: United States
facility: Univ. of Rochester ACTG CRS
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs
state: North Carolina
city: Cleveland
country: United States
facility: Case CRS
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth CRS
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: Pitt CRS
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hosp. ACTG CRS
state: Rhode Island
city: Galveston
country: United States
facility: Univ. of Texas Medical Branch, ACTU
state: Texas
city: Seattle
country: United States
facility: University of Washington AIDS CRS
state: Washington
city: San Juan
country: Puerto Rico
facility: Puerto Rico-AIDS CRS
Study officials:
affiliation: University of Colorado, Denver
name: Robert T. Schooley, MD
role: STUDY_CHAIR
References:
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citation: Schooley RT, Spritzler J, Wang H, Lederman MM, Havlir D, Kuritzkes DR, Pollard R, Battaglia C, Robertson M, Mehrotra D, Casimiro D, Cox K, Schock B; AIDS Clinical Trials Group 5197 Study Team. AIDS clinical trials group 5197: a placebo-controlled trial of immunization of HIV-1-infected persons with a replication-deficient adenovirus type 5 vaccine expressing the HIV-1 core protein. J Infect Dis. 2010 Sep 1;202(5):705-16. doi: 10.1086/655468.
citation: Li JZ, Heisey A, Ahmed H, Wang H, Zheng L, Carrington M, Wrin T, Schooley RT, Lederman MM, Kuritzkes DR; ACTG A5197 Study Team. Relationship of HIV reservoir characteristics with immune status and viral rebound kinetics in an HIV therapeutic vaccine study. AIDS. 2014 Nov 28;28(18):2649-57. doi: 10.1097/QAD.0000000000000478.
citation: Li JZ, Christensen JA, Wang H, Spritzler J, Kuritzkes DR; AIDS Clinical Trials Group A5197 Study Team. Evaluation of HIV-1 ambiguous nucleotide frequency during antiretroviral treatment interruption. J Acquir Immune Defic Syndr. 2012 Sep 1;61(1):19-22. doi: 10.1097/QAI.0b013e318264460f.
citation: Li JZ, Brumme CJ, Lederman MM, Brumme ZL, Wang H, Spritzler J, Carrington M, Medvik K, Walker BD, Schooley RT, Kuritzkes DR; AIDS Clinical Trials Group A5197 Study Team. Characteristics and outcomes of initial virologic suppressors during analytic treatment interruption in a therapeutic HIV-1 gag vaccine trial. PLoS One. 2012;7(3):e34134. doi: 10.1371/journal.pone.0034134. Epub 2012 Mar 30.
citation: Li JZ, Brumme ZL, Brumme CJ, Wang H, Spritzler J, Robertson MN, Lederman MM, Carrington M, Walker BD, Schooley RT, Kuritzkes DR; AIDS Clinical Trials Group A5197 Study Team. Factors associated with viral rebound in HIV-1-infected individuals enrolled in a therapeutic HIV-1 gag vaccine trial. J Infect Dis. 2011 Apr 1;203(7):976-83. doi: 10.1093/infdis/jiq143.