Aids, Cdc Group I
Conditions
Keywords
AIDS vaccines, HIV-1 vaccine, Therapeutic vaccine, Cellular immunity
Brief summary
Treatment: Immunization with peptide-mix and adjuvant. The vaccine should induce cellular immunity against HIV-1. Target group: Untreated healthy individuals with chronic HIV-1 infection. Purpose: The primary purpose is to evaluate tolerability and safety of the vaccine. The secondary purpose is to evaluate the clinical effect of the vaccination treatment as measured by induction of immunity, lowering of viral load, induction of escape mutations in the virus and improvement in the patient CD4 lymphocyte blood counts. The third purpose is to evaluate the feasibility of conducting a therapeutic HIV immunization study in a poorly-resourced African setting. Design: The experiment is designed as a blinded, placebo-controlled phase 1 clinical trial in HIV-1 infected individuals in West Africa. Numbers of individuals: Phase I: 20 fully evaluable HIV-1-infected patients should enter the study (15 vaccine treated and 5 placebo(saline) treated controls).
Detailed description
The HIV infection does not leave lifelong immunity, but leads to break down of the immune system, opportunistic infections and death. The immunity obtained by the infection itself can only partially contain the HIV infection. The purpose with a targeted therapeutic vaccination is therefore in addition to the existing immunity to induce a broader, more powerful and more rationally or better directed immunity than the one induced by the natural HIV-1 infection. This would potentially lower the viral load in the blood making it more difficult to spread the virus to others and prolong the time to AIDS disease and medical treatment. There is a need for new rational vaccination possibilities, able to prevent (HIV) disease, postpone the need for antiretroviral medical treatment, prolong the life, and limit spread of HIV-1 in the population. The present protocol seak to introduce such a new immune treatment principle for HIV-1 infected individuals. In this study, individuals with chronic HIV-1 infection will be vaccinated with selected synthetic HIV immune-peptides representing new discovered conserved target´s on the virus. The vaccine should induce new immunity against several epitope targets on their HIV, whereby the HIV infection may be controlled for a longer time by the immune system. The purpose of the study is primarily to evaluate the safety and tolerability of the vaccine and secondary to evaluate the immunological and antiviral response in the vaccinated individuals.
Interventions
BIOLOGICALAFO-18
18 peptides representing CD8 and CD4 epitopes mainly on HIV-1 in an adjuvants (CAF01)
DRUGSaline
1.2 ml saline intramuscularly
Sponsors
Ministry of the Interior and Health, Denmark
European and Developing Countries Clinical Trials Partnership (EDCTP)
Statens Serum Institut
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1. HIV-1 seropositive with measurable viral load \>10e3 copies/ml and CD4+ T-cell count \>400 CD4+ cells/µl. 2. Not in Antiretroviral Therapy (\>1 year). 3. Male or female with age between 18 and 50 years. 4. Normal values for the area of liver and kidney enzymes, blood cell count with differential counts (e.g. white blood cells, lymphocytes, platelets/thrombocytes) and Hemoglobin 5. Expected to follow the instructions. 6. Written informed consent after oral and written information.
Exclusion criteria
1. Vaccinated with other vaccines within 3 months before the first vaccination. 2. Treated with immune modulating medicine within 3 month before the first immunization. 3. Other important active chronic infectious diseases likely to influence the HIV-1 infection, like HIV-2, HBV, HCV and TB 4. Significant medical disease as judged by the investigators, for example severe asthma/COLD, badly regulated heart disease, insulin-dependent diabetes mellitus. 5. Severe allergy or earlier anaphylactic reactions. 6. Active autoimmune diseases. 7. Simultaneous treatment with other experimental drugs. 8. Laboratory parameters outside the 'normal' range for the area and which are considered clinically significant. 9. Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability and Safety of the Treatment. | up to 6 months after end of treatment | We report here the numbers of participants with vaccine related adverse events degree 3 or 4. Our goal for safety and tolerability was: Fewer than or 3 patients of the 15 vaccine treated show treatment related (reaction 3) side-effects of degree 3 or 4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Induction of New T-cell Immune Response by the Vaccine | up to 6 months after last immunisation | induction of new T-cell immune response against one or more of the vaccine epitopes using Interferon gamma Enzyme Linked Immuno spot assay (IFNg-ELISPOT assay)measuring Spot forming Unis per 1 million periferal blood mononuclear cells (SFU/1 mio PBMCs) above treshold (\> 50 sfu/mio PBMC). |
| Lowering of HIV-1 RNA Viral-load in HIV-1 Immune Responders More Than 1 Log | up to 6 months post immunization | changes (lowering) in Plasma HIV-1 RNA viral-load (measured by Quantitative RT-PCR kit, ROCHE) of more than 1 log |
| Increase in Blood CD4 T-cell Counts | up to 6 months post vaccination | Analyzed: Participants (minus drop-outs and withdrawn) with measured blood CD4 T-cell counts (cells/microliter). Reported: Numbers of participants obtaining an increase in measured blood CD4 T-cell counts post vaccination of \>100 CD4 Tcell per microliter |
Countries
Guinea-Bissau
Participant flow
Recruitment details
medical clinic
Participants by arm
| Arm | Count |
|---|---|
| AFO-18 18 peptides representing CD8 and CD4 epitopes mainly on HIV-1 in an adjuvants (CAF01) | 18 |
| Saline Saline injection | 5 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Saline | AFO-18 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 18 Participants | 23 Participants |
| Age Continuous | 29 years STANDARD_DEVIATION 2 | 34 years STANDARD_DEVIATION 2 | 32 years STANDARD_DEVIATION 2 |
| Region of Enrollment Guinea-Bissau | 5 participants | 18 participants | 23 participants |
| Sex: Female, Male Female | 3 Participants | 17 Participants | 20 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 18 | 0 / 5 |
| serious Total, serious adverse events | 1 / 18 | 1 / 5 |
Outcome results
Primary
Tolerability and Safety of the Treatment.
We report here the numbers of participants with vaccine related adverse events degree 3 or 4. Our goal for safety and tolerability was: Fewer than or 3 patients of the 15 vaccine treated show treatment related (reaction 3) side-effects of degree 3 or 4.
Time frame: up to 6 months after end of treatment
Population: Analyzed: number of participants started minus individuals lost to follow up or participants that withdraw. Thus we include the two individuals where the physician stopped his/her participation because of SAE not related to the vaccine or to the placebo. Reported: numbers of participants with vaccina related SAE
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaccinee | Tolerability and Safety of the Treatment. | 0 participants |
| Placebo | Tolerability and Safety of the Treatment. | 0 participants |
Secondary
Increase in Blood CD4 T-cell Counts
Analyzed: Participants (minus drop-outs and withdrawn) with measured blood CD4 T-cell counts (cells/microliter). Reported: Numbers of participants obtaining an increase in measured blood CD4 T-cell counts post vaccination of \>100 CD4 Tcell per microliter
Time frame: up to 6 months post vaccination
Population: Participants minus drop-outs and withdrawn participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaccinee | Increase in Blood CD4 T-cell Counts | 0 participants with increased CD4 count |
| Placebo | Increase in Blood CD4 T-cell Counts | 0 participants with increased CD4 count |
Secondary
Induction of New T-cell Immune Response by the Vaccine
induction of new T-cell immune response against one or more of the vaccine epitopes using Interferon gamma Enzyme Linked Immuno spot assay (IFNg-ELISPOT assay)measuring Spot forming Unis per 1 million periferal blood mononuclear cells (SFU/1 mio PBMCs) above treshold (\> 50 sfu/mio PBMC).
Time frame: up to 6 months after last immunisation
Population: Analyzed: Participants minus drop-outs and withdrawn participants. Reported: numbers of participants with a new induced ELISPOT Y-cell immune response to the vaccine peptide epitopes
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaccinee | Induction of New T-cell Immune Response by the Vaccine | 6 ELISPOT responders |
| Placebo | Induction of New T-cell Immune Response by the Vaccine | 0 ELISPOT responders |
Secondary
Lowering of HIV-1 RNA Viral-load in HIV-1 Immune Responders More Than 1 Log
changes (lowering) in Plasma HIV-1 RNA viral-load (measured by Quantitative RT-PCR kit, ROCHE) of more than 1 log
Time frame: up to 6 months post immunization
Population: Participants minus drop outs and participants withdrawn by them selves or by the physicians
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaccinee | Lowering of HIV-1 RNA Viral-load in HIV-1 Immune Responders More Than 1 Log | 0 participants with lowering of VL |
| Placebo | Lowering of HIV-1 RNA Viral-load in HIV-1 Immune Responders More Than 1 Log | 0 participants with lowering of VL |