Therapeutic Vaccine for HIV
- In most people who have human immunodeficiency virus (HIV), the immune system cannot control or cure the infection. Antiretroviral therapy drugs can keep the amount of HIV virus low for a long time. However, this treatment does not remove the virus from the body. In the vast majority of patients antiretroviral therapy also will not protect the body from the virus once treatment stops. Researchers want to see if therapeutic vaccination can help people with HIV. Therapeutic vaccination means giving vaccines to treat an infection that someone already has (HIV, in this case). It may help the body's immune system attack the infection. This study will look at different measures of HIV infection after receiving either therapeutic vaccination or a placebo.
- To see whether therapeutic vaccination is safe and can affect how the body responds to HIV infection.
- Individuals between 18 and 65 years of age who have HIV and are taking antiretroviral therapy drugs.
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
- During the screening visit and throughout the study until week 56, participants will continue to take their HIV medications.
- Participants will be divided into two groups. One group will have the study vaccines. The other will have a placebo.
- The first study vaccine or placebo will be given in weeks 4, 12, and 36. The second study vaccine or the placebo will be given in weeks 24 and 48. Blood samples and other tests will be given at each visit.
- After the study visit at week 56, participants will stop their HIV medications until week 72. From weeks 58 through 72, they will come in every 2 weeks for study visits; each visit will take about 1 hour to complete. These visits will look at the body s response to the vaccines and their HIV viral load. After week 72, participants will re-start their HIV medications.
- There will be follow-up study visits from weeks 76 to 96, with blood tests and other studies.
Biological: HIV-1 Multiantigen pDNA Vaccine
Biological: Human IL-12 pDNA
Procedure: In Vivo Electroporation using the TriGri
Biological: rVSVIN HIV Gag Vaccine
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
|Official Title:||A Phase I Randomized, Double-Blind, Placebo-Controlled Study of a Multi-Antigen DNA Vaccine Prime Delivered by In Vivo Electroporation, rVSV Booster Vaccine in HIV-Infected Patients Who Began Antiretroviral Therapy During Acute/Early Infection|
- The rate of occurrence of SAEs or grade 3 or higher AEs that are possibly, probably, or definitely related to one or more of the study agents. [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
- The difference in HIV-1 viral load at 16 weeks following ATI between the vaccine and placebo groups. [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
|Study Start Date:||May 2013|
|Estimated Study Completion Date:||November 2016|
|Estimated Primary Completion Date:||November 2016 (Final data collection date for primary outcome measure)|
Biological: HIV-1 Multiantigen pDNA Vaccine
The advent of combination antiretroviral therapy (cART) has dramatically improved the clinical outcome in human immunodeficiency virus (HIV)-infected individuals through sustained reduction in viral replication. However, it has become clear that cART alone cannot eradicate HIV in infected individuals, likely in part due to the persistence of viral reservoirs in peripheral blood and various tissue compartments. Consequently, a major thrust of HIV research over the past several years has been to develop therapeutic strategies that can eliminate persistent viral reservoirs and boost host immunity to control viral replication upon discontinuation of cART. Therapeutic HIV vaccination is one approach that could potentially achieve these goals through vaccine-induced improvement in HIV-specific immune responses and/or by direct reactivation of HIV-specific CD4+ memory T cells that harbor latent HIV. An effective therapeutic vaccine could augment immunologic control of HIV infection and potentially obviate the need for chronic cART.
The current study is an exploratory randomized, 2-arm (1:1), double-blind, placebo-controlled trial evaluating the safety and efficacy of an HIV-1 multiantigen plasmid DNA (HIV-MAG pDNA) vaccine prime in combination with an interleukin-12 plasmid DNA (IL-12 pDNA) adjuvant delivered by in vivo electroporation followed by a recombinant vesicular stomatitis virus vector containing the HIV-1 gag gene (rVSV HIV gag) booster vaccine in subjects on cART who started therapy during acute or early HIV infection.
Subjects will be randomized to receive placebo or the HIV-MAG pDNA (3000 g) vaccine prime and IL-12 pDNA adjuvant (1000 g) at week 0, 4, 12, and 36, and the rVSV HIV gag booster vaccine (1x107 plaque-forming units) at week 24 and 48. The HIV-MAG pDNA vaccine prime and IL-12 pDNA adjuvant will be administered as 2 IM injections, 1 into each deltoid, with electroporation using the Ichor TDS device, while the rVSV HIV gag booster vaccine will be administered as 2 conventional IM injections, 1 into each deltoid. After the week 56 visit, all subjects will undergo an analytical treatment interruption to determine if the vaccination strategy results in an improved immune control of viral replication, as evidenced by a blunted or absent rebound in HIV plasma viremia. All subjects will be followed through week 96 for safety and efficacy parameters.
The study population includes HIV-infected adults who began cART during acute or early infection. Subjects must be receiving an effective cART regimen, with a CD4 cell count of > 450 cells/mm3 at screening, and they must have documented viral suppression below the limit of detection for greater than1 year. The rationale for testing the study vaccine regimen in this subject population is because these individuals may have a relatively preserved immune function, which could be augmented by therapeutic vaccination.
|Contact: Kathleen R Gittens||(301) email@example.com|
|Contact: Michael C Sneller, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Michael C Sneller, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|