Clinical trial NCT00402142: Dendritic Cell Vaccine in HIV-1 Infection
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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV Infections
Keywords: HIV Infection
Dendritic cell vaccine
Autologous virus
Heat inactivated
HIV Therapeutic Vaccine
Lead sponsor: Hospital Clinic of Barcelona
Sponsor class: OTHER
First posted: 2006-11-22
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 1. 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).
2. To analyze the HIV-1 humoral and cellular immune responses induced by this immune-based therapy.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Confirmed HIV infection
* CD4 \> 450 x 10 6 /L
* baseline VL \>10,000 c/ml before any HAART
* Part I, patients off HAART at least during 6 months
* Part II, Patients on HAART with PVL \< 200 copies/ml at least during 6 months
* Written informed consent .

Exclusion Criteria:

* Patients with failure to HAART
* Patients with B or C symptoms (CDC classification 1993).
* Age \< 18 years old.
* Pregnant or breastfeeding women
* Patients with baseline creatinin \> 2.5 mg/dl
* Patients with baseline GOT/GPT \> 250 UI/L

Primary outcomes:
measure: Comparison of steady state viremia (so-called viral set point) after 6-12 months after vaccination with viremia before HAART.
timeFrame: 6 and 12 months
Secondary outcomes:
measure: 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.
timeFrame: 6 and 12 months
measure: 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.
timeFrame: 6 and 12 months
measure: 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.
timeFrame: 6 and 12 months
measure: HIV-1 specific CTL responses in lymphoid tissue
timeFrame: 0 and 6 months
measure: DC Migration
timeFrame: 0 and 2 weeks
measure: Viral load in semen and vaginal secretions
timeFrame: 0 and 6 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clínic
Study officials:
affiliation: Hospital Clínic
name: Felipe García, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Garcia F, Lejeune M, Climent N, Gil C, Alcami J, Morente V, Alos L, Ruiz A, Setoain J, Fumero E, Castro P, Lopez A, Cruceta A, Piera C, Florence E, Pereira A, Libois A, Gonzalez N, Guila M, Caballero M, Lomena F, Joseph J, Miro JM, Pumarola T, Plana M, Gatell JM, Gallart T. Therapeutic immunization with dendritic cells loaded with heat-inactivated autologous HIV-1 in patients with chronic HIV-1 infection. J Infect Dis. 2005 May 15;191(10):1680-5. doi: 10.1086/429340. Epub 2005 Apr 11.
citation: Garcia F, Climent N, Guardo AC, Gil C, Leon A, Autran B, Lifson JD, Martinez-Picado J, Dalmau J, Clotet B, Gatell JM, Plana M, Gallart T; DCV2/MANON07-ORVACS Study Group. A dendritic cell-based vaccine elicits T cell responses associated with control of HIV-1 replication. Sci Transl Med. 2013 Jan 2;5(166):166ra2. doi: 10.1126/scitranslmed.3004682.
citation: Garcia F, Climent N, Assoumou L, Gil C, Gonzalez N, Alcami J, Leon A, Romeu J, Dalmau J, Martinez-Picado J, Lifson J, Autran B, Costagliola D, Clotet B, Gatell JM, Plana M, Gallart T; DCV2/MANON07- AIDS Vaccine Research Objective Study Group. A therapeutic dendritic cell-based vaccine for HIV-1 infection. J Infect Dis. 2011 Feb 15;203(4):473-8. doi: 10.1093/infdis/jiq077. Epub 2011 Jan 13.
citation: Andres C, Plana M, Guardo AC, Alvarez-Fernandez C, Climent N, Gallart T, Leon A, Clotet B, Autran B, Chomont N, Gatell JM, Sanchez-Palomino S, Garcia F. HIV-1 Reservoir Dynamics after Vaccination and Antiretroviral Therapy Interruption Are Associated with Dendritic Cell Vaccine-Induced T Cell Responses. J Virol. 2015 Sep;89(18):9189-99. doi: 10.1128/JVI.01062-15. Epub 2015 Jun 24.
citation: Gil C, Climent N, Garcia F, Hurtado C, Nieto-Marquez S, Leon A, Garcia MT, Rovira C, Miralles L, Dalmau J, Pumarola T, Almela M, Martinez-Picado J, Lifson JD, Zamora L, Miro JM, Brander C, Clotet B, Gallart T, Gatell JM. Ex vivo production of autologous whole inactivated HIV-1 for clinical use in therapeutic vaccines. Vaccine. 2011 Aug 5;29(34):5711-24. doi: 10.1016/j.vaccine.2011.05.096. Epub 2011 Jun 14.