HIV Infections
Conditions
Keywords
HIV, Vaccination
Brief summary
The purpose of this study is to determine if vaccination before a structured treatment interruption (STI) is associated with an improvement in immune function, resulting in a delayed and reduced rebound in the amount of HIV virus in the blood.
Detailed description
Volunteers will be randomly assigned to receive the vaccines or matching placebos before interrupting their antiretroviral therapy at week 24. Dosage: Remune(TM) 1 ml i.m.\* at weeks 0, 12, and 20; ALVAC 1 ml i.m.\* at weeks 8,12, 16, and 20. \* i.m.: injected in a muscle
Interventions
BIOLOGICALRemune and ALVAC
* Group 1) Remune™ (1ml i.m.) at weeks 0, 12 and 20 and ALVAC (1 ml i.m.) at weeks 8, 12, 16 and 20); * Group 2) Remune™ placebo (1ml i.m.) at weeks 0, 12 and 20 and ALVAC (1 ml i.m.) at weeks 8, 12, 16 and 20; or * Group 3) Remune™ placebo (1ml i.m.) at weeks 0, 12 and 20 and ALVAC placebo (1 ml i.m.) at weeks 8, 12, 16 and 20.
Sponsors
Canadian Institutes of Health Research (CIHR)
Ontario HIV Treatment Network
CIHR Canadian HIV Trials Network
Ottawa Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented HIV infection (by serology) * HIV RNA level below 50 copies/ml for at least two years * Receiving at least 2 antiretroviral agents including at least 1 protease inhibitor or 1 non-nucleoside reverse transcriptase inhibitor at time of screening * Have CD4 counts above 500 cells/ul * Have CD4/CD8 ratio above 0.5 * Have never had a CD4 count below 250 * No previous AIDS-defining opportunistic infection * No previous cancer chemotherapy or other system immunosuppressive therapy (excluding brief courses \[\<= 1 month\] of prednisone or its equivalent) * Able to provide informed consent
Exclusion criteria
* Hepatitis B surface antigen positive * Hepatitis C antibody positive * AST, ALT, ALP, creatinine, urea above three times the normal upper limit * Blood abnormalities (hemoglobin lower than 100, white blood cell count \[WBC\] lower than 1500 or platelets lower than 100) * Allergies to components of Remune™ or ALVAC * Contraindications to vaccine components * Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to Detectable Virus in the Remune Plus ALVAC Group and the Placebo Group | Up to week 48 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Detectable Virus in the ALVAC Alone Group and the Placebo Group | Up to week 48 | — |
| Time to Rebound of Plasma HIV RNA Level to 10,000 Copies/ml | Up to week 48 | — |
| Viral Set-point | Up to week 48 | Viral set-point is the viral load (HIV RNA) that the body settles at within a few weeks to months after infection with HIV. |
| Magnitude of Viral Rebound | Up to week 48 | Magnitude of viral rebound is the amount of HIV viral load an infected person who was previously on ART and suppressed below clinical detection rebounds to following ART stoppage. This will typically be compared to the viral load before starting ART or Viral set-point discussed earlier. |
| HIV-specific Immune Function | at week 48 | — |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ALVAC With Remune Remune™ (1ml i.m.) at weeks 0, 12 and 20 and ALVAC (1 ml i.m.) at weeks 8, 12, 16 and 20. | 19 |
| ALVAC With Remune Placebo Remune™ placebo (1ml i.m.) at weeks 0, 12 and 20 and ALVAC (1 ml i.m.) at weeks 8, 12, 16 and 20. | 18 |
| Both Placebos Remune™ placebo (1ml i.m.) at weeks 0, 12 and 20 and ALVAC placebo (1 ml i.m.) at weeks 8, 12, 16 and 20. | 15 |
| Total | 52 |
Baseline characteristics
| Characteristic | ALVAC With Remune | ALVAC With Remune Placebo | Both Placebos | Total |
|---|---|---|---|---|
| Age, Continuous | 39.7 years | 41.5 years | 43.4 years | 41.8 years |
| Baseline CD4% | 37.1 percent | 38.0 percent | 35.0 percent | 37.2 percent |
| Baseline CD4 cell count | 771 cells/ul | 658 cells/ul | 848 cells/ul | 768 cells/ul |
| CD4 nadir | 347 cells/ul | 326 cells/ul | 368 cells/ul | 353 cells/ul |
| Duration on ART | 3.61 years | 5.15 years | 5.18 years | 4.89 years |
| Pre-HAART HIV-RNA | 4.4 log 10 (copies/ml) | 4.0 log 10 (copies/ml) | 4.2 log 10 (copies/ml) | 4.1 log 10 (copies/ml) |
| Presence of 'protective' HLA allele | 3 participants | 2 participants | 4 participants | 9 participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 3 Participants | 12 Participants |
| Sex: Female, Male Male | 15 Participants | 13 Participants | 12 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 19 | 10 / 18 | 4 / 15 |
| serious Total, serious adverse events | 0 / 19 | 0 / 18 | 0 / 15 |
Outcome results
Primary
Time to Detectable Virus in the Remune Plus ALVAC Group and the Placebo Group
Time frame: Up to week 48
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ALVAC With Remune | Time to Detectable Virus in the Remune Plus ALVAC Group and the Placebo Group | 24.5 days |
| Both Placebos | Time to Detectable Virus in the Remune Plus ALVAC Group and the Placebo Group | 13.5 days |
Secondary
HIV-specific Immune Function
Time frame: at week 48
Population: Data not collected for this assessment.
Secondary
Magnitude of Viral Rebound
Magnitude of viral rebound is the amount of HIV viral load an infected person who was previously on ART and suppressed below clinical detection rebounds to following ART stoppage. This will typically be compared to the viral load before starting ART or Viral set-point discussed earlier.
Time frame: Up to week 48
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ALVAC With Remune | Magnitude of Viral Rebound | 4.8 log10 copies/ml |
| Both Placebos | Magnitude of Viral Rebound | 5.0 log10 copies/ml |
| Both Placebos | Magnitude of Viral Rebound | 5.0 log10 copies/ml |
Secondary
Time to Detectable Virus in the ALVAC Alone Group and the Placebo Group
Time frame: Up to week 48
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ALVAC With Remune | Time to Detectable Virus in the ALVAC Alone Group and the Placebo Group | 23.0 days |
| Both Placebos | Time to Detectable Virus in the ALVAC Alone Group and the Placebo Group | 13.5 days |
Secondary
Time to Rebound of Plasma HIV RNA Level to 10,000 Copies/ml
Time frame: Up to week 48
Population: Only participants who reached 10,000 copies/ml are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ALVAC With Remune | Time to Rebound of Plasma HIV RNA Level to 10,000 Copies/ml | 30.0 days |
| Both Placebos | Time to Rebound of Plasma HIV RNA Level to 10,000 Copies/ml | 31.0 days |
| Both Placebos | Time to Rebound of Plasma HIV RNA Level to 10,000 Copies/ml | 24.5 days |
Secondary
Viral Set-point
Viral set-point is the viral load (HIV RNA) that the body settles at within a few weeks to months after infection with HIV.
Time frame: Up to week 48
Population: Only participants whose viral loads reached a steady state are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ALVAC With Remune | Viral Set-point | 4.4 log10 copies/ml |
| Both Placebos | Viral Set-point | 4.2 log10 copies/ml |
| Both Placebos | Viral Set-point | 4.5 log10 copies/ml |