HIV-1 infection, seroposoitive anti-retroviral treatment, cellular immunity, early proteins, Tat, Rev, Nef
Conditions
Interventions
Four monthly immunizations with autologous dendritic cells, expressing TAT, REV and NEF, ten million each. Sub cutaneous and intra-dermal application of the formulations at three distinct sites.
Cont
Control to stop therapy from historical cases (Tristan project).
VACCINATION PLAN
Dendritic cells:
Each DC-based vaccine will be administered at a dose of 10 x 106 DC on every day of vaccination. T
2. On each vaccination day, the three autologous DC vaccines (10 x 106 DC electroporated with Tat, Rev
or Nef encoding mRNA) will be administered intradermally (50% of the vaccine volume) and
subcutan
3. All patients will be treated as outpatients and must be observed for 2 hours following injection. Drugs
and equipment will be immediately available to treat possible anaphylaxis. Beginning the day
Sponsors
Erasmus MC, Rotterdam, Vrije Universiteit Brussel, Brussel
K. Thielemans, MD, PhD
Director Laboratory of Molecular and Cellular Therapy
Medical School Vrije Universiteit Brussel
Laarbeeklaan 103 B-1090 Brussels
Tel: + 32 (0)2 477 45 69
Fax: + 32 (0)2 477 45 68
e-mail: Kris.Thielemans@vub.ac.be
Eligibility
Inclusion criteria
Inclusion criteria: 1. HIV-1 seropositive; 2. >1 year on stable HAART; 3. Viral load: 3 months; 4. CD4 T cells: >500 cells/ul for >3 months and a nadir of > 300 cells/ul; 5. >18 years of age.
Exclusion criteria
Exclusion criteria: 1. Acute or serious illness 50 copies/ml in 3 months before entry; 3. CD4 T cell count <500 cells/ml; 4. History of lymph node irradiation; 5. Prior use of any HIV vaccine and/or non-established therapy; 6. History of allergy to neomycin or history of other serious allergic reaction; 7. Pregnancy and breastfeeding; 8. History of immune modulators or suppressors <30 days prior to study entry; 9. Active drug or alcohol abuse or dependence or psychiatric abnormality that would interfere with adherence to the study requirements; 10. Known HIV-1 seroconversion within one year prior to study entry, infection with HBV, HCV or HTLV-I or II.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine safety and toxicity of the subcutaneous and intradermal (SC/ID) administration of autologous dendritic cells (DC) electroporated with mRNA encoding Tat, Rev and Nef in HIV-1 infected patients who are virologically and immunologically responding to HAART. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To assess the ability of mRNA electroporated autologous DC, administrated SC/ID, to enhance HIV-specific T-cell responses against Tat, Rev and Nef in HIV-1 infected patients under stable HAART; 2. To assess the kinetics of the HIV viral load rebound after withdrawal of HAART in the setting of an analytical treatment interruption (ATI), in HIV-1 infected patients to whom autologous dendritic cells electroporated with mRNA encoding Tat, Rev or Nef have been administered; 3. To assess the duration of the period off HAART in the study patients; 4. To determine whether genotypical variation occurs in the genes targeted by the vaccine and whether this correlates with immune escape. | — |
Contacts
Public ContactA.D.M.E. Osterhaus
P.O. Box 2040
Outcome results
None listed