Dendritic Cell Vaccine in HIV-1 Infection
Recruitment status was Recruiting
- To study the efficacy of a therapeutic HIV vaccine consisting of autologous myeloid dendritic cells pulsed ex vivo with high doses of inactivated autologous HIV-1, in HIV-1 infected patients in a very early stages of the disease (CD4 > 450 x 10 6 /L).
- To analyze the HIV-1 humoral and cellular immune responses induced by this immune-based therapy.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Phase II Study of Autologous Myeloid Dendritic Cells as a "Cellular Adjuvant" for a Therapeutic HIV-1 Vaccine in Early Stage HIV-1+ Patients (DCV-2).|
- Comparison of steady state viremia (so-called viral set point) after 6-12 months after vaccination with viremia before HAART.
- Proportion with evidence of HIV-specific CTL comparing end of immune-based therapy, and end of trial (week 48) with start of immune-based therapy.
- Proportion with evidence of HIV-specific T-cell proliferative response comparing end of immune-based therapy, and end of trial (week 48) with start of immune-based therapy.
- Proportion with evidence of HIV-specific neutralizing activity of serum comparing end of immune-based therapy, and end of trial (week 48) with start of immune-based therapy.
- HIV-1 specific CTL responses in lymphoid tissue
- DC Migration
- Viral load in semen and vaginal secretions
|Study Start Date:||November 2006|
|Estimated Study Completion Date:||December 2009|
|Estimated Primary Completion Date:||December 2009 (Final data collection date for primary outcome measure)|
Our group has reported recently the first human trial of 4 therapeutic immunizations at six-week intervals with autologous monocyte-derived dendritic cells (MD-DC) loaded with heat-inactivated autologous HIV in 12 HIV infected patients who had been receiving highly active antiretroviral therapy (HAART) since early chronic infection. Autologous HIV was concentrated from plasma (1,500 ml) obtained by plasmapheresis after a 3-month HAART interruption (STOP1) performed 78 weeks before therapeutic immunizations, and HAART was discontinued again (STOP2) after therapeutic immunization. There was a decrease of set-point plasma viral load (PVL) >= 0.5 log after 24 weeks off HAART in 4 out of 12 patients. In addition, we observed a significant lengthening in mean doubling time of PVL rebound (p= 0.01), and significant decreases in the area under the curve of PVL rebound (p= 0.02) and in the mean peak PVL (p= 0.004) during the 12 weeks after STOP 2 compared with STOP1. This virological response was associated with a weak but significant increase in HIV-1 specific CD4 lymphoproliferative response, and with changes in HIV-1 specific CD8+ T-cell responses in peripheral blood and in lymphoid CTL cells after immunization. In lymphoid tissue, we also observed a trend towards a better control of HIV-1 replication coupled with an increase of CD4+ and CTL cells. No significant virological or immunological changes occurred in controls. We show that a therapeutic vaccine with autologous MD-DC pulsed with heat inactivated autologous HIV-1 is feasible, safe and well tolerated and elicited weak and transient cellular immune responses against HIV, associated with a partial and transient control of HIV replication in some patients.
we hypothesized that a DC vaccine pulsed with higher amount of autologous virus obtained by culture could be more effective than the vaccine we used.
|Contact: Felipe García, MD, PhDfirstname.lastname@example.org|
|Barcelona, Spain, 08036|
|Contact: Felipe García, MD, PhD 34932275586 email@example.com|
|Principal Investigator: Felipe García, MD, PhD|
|Sub-Investigator: Josep M Gatell, MD, PhD|
|Sub-Investigator: Meritxell Nomdedeu, MD, PHD|
|Principal Investigator:||Felipe García, MD, PhD||Hospital Clínic|