Dendritic Cell Vaccine in HIV-1 Infection - Full Text View

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Biological: Dendritic cell vaccine Biological: non pulsed dendritic cell untreated patients Biological: pulsed dendritic cell vaccine Biological: dendritic cell vaccine Biological: non pulsed dendritic cell vaccine	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Care Provider, 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).

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Further study details as provided by Felipe Garcia, Hospital Clinic of Barcelona:

Primary Outcome Measures:

Comparison of steady state viremia (so-called viral set point) after 6-12 months after vaccination with viremia before HAART. [ Time Frame: 6 and 12 months ]

Secondary Outcome Measures:

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. [ Time Frame: 6 and 12 months ]
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. [ Time Frame: 6 and 12 months ]
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. [ Time Frame: 6 and 12 months ]
HIV-1 specific CTL responses in lymphoid tissue [ Time Frame: 0 and 6 months ]
DC Migration [ Time Frame: 0 and 2 weeks ]
Viral load in semen and vaginal secretions [ Time Frame: 0 and 6 months ]


Enrollment:	60
Study Start Date:	November 2006
Study Completion Date:	December 2011
Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Pulsed dendritic cells untreated patients Untreated patients receiving a dendritic cell based vaccine pulsed with autologous heat iactivated virus	Biological: Dendritic cell vaccine 107 DC subcutaneous 3 doses every 2 weeks
Placebo Comparator: non pulsed dendritic cells untreated patients	Biological: non pulsed dendritic cell untreated patients 107 DC subcutaneous 3 doses every 2 weeks
Active Comparator: pulsed dendritic cell treated patient treated patients will be immunized with a dendritic cell vaccine pulsed with heat inactivated autologous virus immediately before art interruption	Biological: pulsed dendritic cell vaccine 107 DC subcutaneous 3 doses every 2 weeks
Active Comparator: pulsed dendritic cell in treated patients patients will be immunized with a dendritic cell vaccine pulsed with heat inactivted autologous virus immediately after interruption of art	Biological: dendritic cell vaccine 107 DC subcutaneous 3 doses every 2 weeks
Placebo Comparator: non pulsed dendritic cells	Biological: non pulsed dendritic cell vaccine 107 DC subcutaneous 3 doses every 2 weeks

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


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00402142

Locations


Spain
Hospital Clínic
Barcelona, Spain, 08036

Sponsors and Collaborators

Hospital Clinic of Barcelona

Investigators


Principal Investigator:	Felipe García, MD, PhD	Hospital Clínic

More Information

Publications:

García F, Climent N, Guardo AC, Gil C, León A, Autran B, Lifson JD, Martínez-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.

García F, Climent N, Assoumou L, Gil C, González N, Alcamí J, León A, Romeu J, Dalmau J, Martínez-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.

García F, Lejeune M, Climent N, Gil C, Alcamí J, Morente V, Alós L, Ruiz A, Setoain J, Fumero E, Castro P, López A, Cruceta A, Piera C, Florence E, Pereira A, Libois A, González N, Guilá M, Caballero M, Lomeña F, Joseph J, Miró 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. Epub 2005 Apr 11.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Andrés C, Plana M, Guardo AC, Alvarez-Fernández C, Climent N, Gallart T, León A, Clotet B, Autran B, Chomont N, Gatell JM, Sánchez-Palomino S, García 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.

Gil C, Climent N, García F, Hurtado C, Nieto-Márquez S, León A, García MT, Rovira C, Miralles L, Dalmau J, Pumarola T, Almela M, Martinez-Picado J, Lifson JD, Zamora L, Miró 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.


Responsible Party:	Felipe Garcia, Principal investigator, Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier:	NCT00402142 History of Changes
Other Study ID Numbers:	DCV-02/MANON07
Study First Received:	November 17, 2006
Last Updated:	February 25, 2014

Keywords provided by Felipe Garcia, Hospital Clinic of Barcelona:


HIV Infection Dendritic cell vaccine Autologous virus Heat inactivated HIV Therapeutic Vaccine

Additional relevant MeSH terms:


Infection Communicable Diseases HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases	Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Vaccines Immunologic Factors Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 17, 2017