HIV Infections
Conditions
Keywords
dendritic cell, therapeutic vaccine, HIV-1, apoptotic cells, Phase I/II
Brief summary
This study aims to look at the safety and tolerability of immunization with dendritic cell vaccine prepared using the patient's own cells and virus. It also aims to explore the virologic efficacy of the vaccine as determined by a decrease in the viral load 12 weeks after analytic treatment interruption.
Detailed description
This is a phase I/II, open label, single-arm, single-site clinical trial designed to evaluate the safety and antiviral activity of the ApB DC vaccine, a therapeutic vaccine derived from autologous dendritic cells loaded with autologous HIV-1 infected apoptotic cells. The study will be conducted in three phases. The first is the pre-vaccination phase that includes study entry, isolation of autologous virus, and initiation of antiretroviral therapy. Once the patient's viral load has been suppressed to undetectable levels (\<50 copies/mL) and sufficient virus has been isolated, the second phase will begin. This includes leukapheresis in order to harvest monocytes and lymphocytes necessary for vaccine preparation. Three vaccine doses will be administered subcutaneously every other week. Six weeks after the last vaccination, the third phase, analytic treatment interruption (ATI) phase, will begin. A fourth, booster dose of vaccine will be given two weeks after the start of treatment interruption. The treatment interruption will be continued for twelve weeks after which the primary HIV provider will decide whether or not antiretroviral therapy should be restarted. CD4 and viral load will be closely monitored throughout the study especially during treatment interruption. Follow-up will be continued for 24 weeks after the 12-week treatment interruption.
Interventions
BIOLOGICALAutologous HIV-1 ApB DC Vaccine
Autologous dendritic cells pulsed with autologous, inactivated HIV-1 infected, apoptotic cells given subcutaneously 3 times every other week plus a booster dose 2 weeks after start of treatment interruption
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Sharon Riddler
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed HIV-1 infection. * CD4 greater than or equal to 350 cells/mL within 8 weeks prior to study entry. * Plasma HIV-1 RNA level of 5000-100,000 copies/mL within 8 weeks prior to study entry. * Antiretroviral therapy naive. * Willingness to interrupt ART for at least 12 weeks. * Written informed consent.
Exclusion criteria
* Treatment within 30 days prior to study entry with systemic steroids or other immunosuppressives, or any underlying disease which may require use of such medications during the study period. * Receipt of any vaccinations other than routine ones within 6 months of study entry * Pregnancy or breastfeeding * Previous or current CDC Category C event * Receipt of any investigational product within 12 weeks prior to study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Autologous HIV-1 ApB DC Vaccine. | 80 weeks | AE graded by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, version 1.0, December 2004 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Virologic Efficacy (HIV-1 Viral Load at End of ATI Minus Viral Load Prior to ART) | at the end of 12 weeks treatment interruption | Log10 Change in HIV RNA set point comparing pre-ART to 12 weeks after treatment interruption |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Autologous HIV-1 ApB DC Vaccine Subjects who will receive ApB Dendritic cell vaccine
Autologous HIV-1 ApB DC Vaccine: Autologous dendritic cells pulsed with autologous, inactivated HIV-1 infected, apoptotic cells given subcutaneously 3 times every other week plus a booster dose 2 weeks after start of treatment interruption | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Autologous HIV-1 ApB DC Vaccine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 37.9 years |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Safety and Tolerability of Autologous HIV-1 ApB DC Vaccine.
AE graded by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, version 1.0, December 2004
Time frame: 80 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Autologous HIV-1 ApB DC Vaccine | Safety and Tolerability of Autologous HIV-1 ApB DC Vaccine. | 2 participants with Grade 3 events related |
Secondary
Virologic Efficacy (HIV-1 Viral Load at End of ATI Minus Viral Load Prior to ART)
Log10 Change in HIV RNA set point comparing pre-ART to 12 weeks after treatment interruption
Time frame: at the end of 12 weeks treatment interruption
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autologous HIV-1 ApB DC Vaccine | Virologic Efficacy (HIV-1 Viral Load at End of ATI Minus Viral Load Prior to ART) | -0.21 log10 HIV RNA |