HIV-1 Infection, HIV Infections
Conditions
Keywords
HIV vaccine, Dendritic cells, treatment experienced
Brief summary
The purpose of the study is to find out whether an experimental autologous dendritic cell vaccine is safe, well tolerated, and whether it can strengthen the immune system's response to HIV.
Detailed description
This is a randomized trial to evaluate whether mRNA-transfected dendritic cell vaccination is safe and immunogenic in HIV-infected participants who are on antiretroviral therapy.
Interventions
BIOLOGICALmRNA-transfected autologous dendritic cells
Injections will be administered intradermally at weeks 0, 2, 6 and 10.
BIOLOGICALautologous dendritic cells with no mRNA transfection
Injections will be administered intradermally at weeks 0, 2, 6 and 10.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* HIV-1 positive * CD4+ T Cell count \>200 * Undetectable HIV viral load for 6 months prior to screening * On antiretroviral treatment for 12 months prior to screening
Exclusion criteria
* Hepatitis C positive * Detectable HIV viral load within 6 months prior to study entry * Females who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of the DC Vaccine (as Measured by Frequency of Adverse Events) | After vaccination | Number of participants with grade 3 or 4 adverse events related to vaccination |
| Change From Baseline to Week 14 in ELISPOT Response to Gag and Nef | Baseline and 14 weeks | Immunogenicity was measure by interferon gamma enzyme-linked immunospot (ELISPOT) assay. The number of spot forming cells per million PBMC was determined at each time point. The fold ratio represents week 14 value divided by value at baseline. |
Secondary
| Measure | Time frame |
|---|---|
| T Cell Proliferation | Baseline to week 14 |
| IL2 and IFN Gamma Production | Baseline to week 14 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| mRNA-transfected Autologous Dendritic Cell Vaccine. mRNA-transfected autologous dendritic cells: Injections will be administered intradermally at weeks 0, 2, 6 and 10. | 10 |
| Autologous Dendritic Cells Without Transfected mRNA. Dendritic cell vaccine without transfected mRNA.
Autologous dendritic cells not transfected with mRNA.: Injections will be administered intradermally at weeks 0, 2, 6 and 10. | 5 |
| Total | 15 |
Baseline characteristics
| Characteristic | mRNA-transfected Autologous Dendritic Cell Vaccine. | Autologous Dendritic Cells Without Transfected mRNA. | Total |
|---|---|---|---|
| Age, Continuous | 44 years | 49 years | 46.7 years |
| Region of Enrollment United States | 10 participants | 5 participants | 15 participants |
| Sex: Female, Male Female | 3 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Change From Baseline to Week 14 in ELISPOT Response to Gag and Nef
Immunogenicity was measure by interferon gamma enzyme-linked immunospot (ELISPOT) assay. The number of spot forming cells per million PBMC was determined at each time point. The fold ratio represents week 14 value divided by value at baseline.
Time frame: Baseline and 14 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| mRNA-transfected Autologous Dendritic Cells | Change From Baseline to Week 14 in ELISPOT Response to Gag and Nef | Gag ELISPOT | 1.06 fold ratio |
| mRNA-transfected Autologous Dendritic Cells | Change From Baseline to Week 14 in ELISPOT Response to Gag and Nef | Nef ELISPOT | 1.15 fold ratio |
| Dendritic Cell Vaccine Without Transfected mRNA. | Change From Baseline to Week 14 in ELISPOT Response to Gag and Nef | Gag ELISPOT | 1.058 fold ratio |
| Dendritic Cell Vaccine Without Transfected mRNA. | Change From Baseline to Week 14 in ELISPOT Response to Gag and Nef | Nef ELISPOT | 1.021 fold ratio |
Primary
Safety of the DC Vaccine (as Measured by Frequency of Adverse Events)
Number of participants with grade 3 or 4 adverse events related to vaccination
Time frame: After vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| mRNA-transfected Autologous Dendritic Cells | Safety of the DC Vaccine (as Measured by Frequency of Adverse Events) | 0 participants |
| Dendritic Cell Vaccine Without Transfected mRNA. | Safety of the DC Vaccine (as Measured by Frequency of Adverse Events) | 0 participants |
Secondary
IL2 and IFN Gamma Production
Time frame: Baseline to week 14
Population: Results from these assays were too variable to be interpretable.
Secondary
T Cell Proliferation
Time frame: Baseline to week 14
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| mRNA-transfected Autologous Dendritic Cells | T Cell Proliferation | CD4 Gag proliferative response | 2.465 fold change |
| mRNA-transfected Autologous Dendritic Cells | T Cell Proliferation | CD4 Nef Proliferative response | 2.292 fold change |
| Dendritic Cell Vaccine Without Transfected mRNA. | T Cell Proliferation | CD4 Gag proliferative response | 0.717 fold change |
| Dendritic Cell Vaccine Without Transfected mRNA. | T Cell Proliferation | CD4 Nef Proliferative response | 0.363 fold change |