HIV Eradication Through Cord-blood Transplantation (HIVECT)
Allogeneic hematopoietic cell transplantation from a CCR5 Δ32/Δ32 unrelated donor, performed for the first time in the "Berlin patient", provides the only evidence to date of long-term control of HIV infection. Stringent criteria to select human leukocyte antigen (HLA)-matched conventional donors and low prevalence of the CCR5 Δ32/Δ32 homozygous genotype (<1%) made the pursuit of "patient number 2" unsuccessful for many years. Cord blood (CB) transplantation allows more permissive HLA-matching criteria, making the search for HLA-compatible Δ32/Δ32 CB units potentially feasible for transplantation of HIV-infected individuals.
The investigator team involved in this trial has recently reported the first such case of CCR5 delta32/delta32 CB transplantation in a patient with HIV infection, showing a reduction of the patient's latent viral reservoir and, upon achievement of full CB chimerism, resistance of his CD4 T-lymphocytes to infection by HIV. This proof of concept led the Spanish National Transplant Organization (ONT) to generate an inventory of over 150 CCR5 Δ32/Δ32 CB units readily available for transplant.
From this initial evidence and repository of CB units, financial support from the Fundación Mutua Madrileña (FMM) has allowed the investigators to launch this first pilot clinical trial in this indication. The study was launched in January 2016 at Hospital Universitario Puerta de Hierro Majadahonda. All HIV virology and reservoir analyses are carried out by the AIDS Immunopathology Unit at the Spanish Instituto de Salud Carlos III. Three additional transplant centres in Spain will also shortly open the trial.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Prospective Clinical Research Protocol of Allogeneic CCR5 delta32/delta32 Cord Blood Cell Transplantation to Cure HIV Infection|
- HIV infection and viral reservoir - Cell-associated total HIV-1 DNA in CD4 T cells from peripheral blood and from gut-associated lymphoid tissue (GALT): Expressed in copies per million cells. [ Time Frame: Between 6-12 months: following discontinuation of antiretroviral therapy upon full CCR5 delta32/delta32 cord blood chimerism ]
- HIV infection and viral reservoir - Viral copies in plasma and culture supernatants by Single Copy Assay and COBAS AMPLICOR HIV-1 Monitor v.1.5: Expressed in copies per mL. [ Time Frame: Between 6-12 months: following discontinuation of antiretroviral therapy upon full CCR5 delta32/delta32 cord blood chimerism ]
- Ex vivo HIV-1 infection tests on CCR5 d32/d32-derived recipients CD4 T cells - Using patient's primary isolates and laboratory strains of HIV-1 with CCR5 and CXCR4 tropism: Expressed in ng/mL of p24 ELISA. [ Time Frame: Between 6-12 months: following discontinuation of antiretroviral therapy upon full CCR5 delta32/delta32 cord blood chimerism ]
|Study Start Date:||June 2016|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||December 2018 (Final data collection date for primary outcome measure)|
Experimental: Study treatment
Allogeneic transplantation with CCR5 delta32/delta32 hematopoietic cells from cord blood.
|Other: CCR5 delta32/delta32 cord blood transplantation|
Please refer to this study by its ClinicalTrials.gov identifier: NCT02923076
|Contact: María Esther Martínez Muñoz||0034 email@example.com|
|Contact: Isabel Salcedo||0034 firstname.lastname@example.org|
|Hospital Universitario Puerta de Hierro- Majadahonda||Recruiting|
|Majadahonda, Madrid, Spain, 28008|
|Contact: María Esther Martínez Muñoz 0034 911917809 email@example.com|
|Contact: Isabel Salcedo 0034 911916481 firstname.lastname@example.org|
|Principal Investigator:||Rafael Duarte Palomino||Hospital Universitario Puerta de Hierro- Majadahonda|