HIV/AIDS Fact Sheet

CIRM funds many projects seeking to better understand HIV/AIDS and to translate those discoveries into new therapies.

Description

HIV, or the human immunodeficiency virus, is a virus that infects cells of the immune system, undermining the body’s ability to fight infection and disease. Eventually infection can lead to symptoms of AIDS (Acquired Immune Deficiency Syndrome), which includes susceptibility to infections, cancers and other diseases, and eventually causes death. According to the CDC, more than 1.1 million people in the U.S. are infected with HIV at this moment.

Stem cell approaches to treating people with HIV primarily involve replacing the person’s immune system with one that the virus can’t infect. Hope that this approach could work were boosted in late 2010 when scientists reported that Timothy Ray Brown, also known as the "Berlin Patient”, had effectively had his HIV “cured”. As part of a treatment for leukemia, Brown had received a bone marrow transplant that came from a donor whose cells were resistant to HIV infection.

The person who donated the bone marrow had a genetic mutation in a gene called CCR5, which makes a protein that is required for HIV to enter cells. Without CCR5, HIV wasn’t able to infect these replacement immune cells and Brown has been able to go off his medications.

The problem is that there aren’t enough people with naturally occurring CCR5 mutations to serve as bone marrow donors for all HIV patients. Instead, scientists are hoping to create CCR5 mutations. They first plan to remove the blood-forming stem cells in a person’s bone marrow and mutate the CCR5 gene. The idea is that those genetically altered cells would then repopulate the person’s blood system with one that lacks CCR5 and that HIV won’t be able to infect.

Clinical Stage Programs

City of Hope

The City of Hope team plans to mutate the CCR5 gene using a technology called a zinc finger nuclease, which is essentially a pair of molecular scissors developed by Sangamo Biosciences that snips an exact spot on the CCR5 gene. Early evidence in animals suggests that when those cells are reintroduced, they create an immune system that HIV can’t infect. The team has begun a clinical trial with the procedure.

Calimmune

The Calimmune team is using a method called RNA interference to block the CCR5 gene from generating a protein. A blood system generated from these cells will lack CCR5 and block HIV infection. The team has completed a Phase 1 clinical trial with the procedure.

University of California, Davis

The team at is taking a patient’s blood forming stem cells and inserting 3 anti-HIV genes into them and then returning them to the individual. The anti-HIV genes are then passed on to all new immune system cells and make them resistant to HIV. Because AIDS-related lymphoma is linked to the constant immune cell stimulation caused by HIV infection, getting rid of the virus should prevent return of the cancer.

University of California, San Francisco

The team will take a patient’s blood and extract T cells, a type of immune cell. The T cells are then genetically modified to express two different chimeric antigen receptors (CAR), which enable the newly created duoCAR-T cells to recognize and destroy HIV infected cells. The modified T cells are then reintroduced back into the patient. The goal of this one-time therapy is to act as a long-term control of HIV with patients no longer needing to take ART, in effect a form of HIV cure.

Read a summary of this project

Jeff Sheehy, HIV/AIDS patient advocate member of the CIRM Governing Board, and John Zaia, leader of the City of Hope CIRM HIV Disease Team, discuss stem cell transplant strategies for the treatment of HIV/AIDS.

CIRM Grants Targeting HIV/AIDS

Researcher name	Institution	Grant Title	Grant Type	Award Amount
David DiGiusto	City of Hope, Beckman Research Institute	Development of RNA-based approaches to stem cell gene therapy for HIV	Early Translational II	$3,097,160
Scott Kitchen	University of California, Los Angeles	Engineering Lifelong Cellular Immunity to HIV	Quest - Discovery Stage Research Projects	$1,701,178
John Zaia	City of Hope, Beckman Research Institute	ZINC FINGER NUCLEASE-BASED STEM CELL THERAPY FOR AIDS	Disease Team Research I	$14,536,969
Xiuli Wang	City of Hope, Beckman Research Institute	CMV-specific T cells expressing anti-HIV CAR and CMV vaccine boost as immunotherapy for HIV/AIDS	Late Stage Preclinical Projects	$3,812,797
Irvin Chen	University of California, Los Angeles	HPSC based therapy for HIV disease using RNAi to CCR5.	Disease Team Research I	$9,905,604
Steven Deeks	University of California, San Francisco	Anti-HIV duoCAR-T cell therapy for HIV infection	Clinical Trial Stage Projects	$8,970,732
Irvin Chen	University of California, Los Angeles	Genetic modification of the human genome to resist HIV-1 infection and/or disease progression	SEED Grant	$616,800
Brian Lawson	The Scintillon Institute	An hematopoietic stem-cell-based approach to treat HIV employing CAR T cells and anti-HIV broadly neutralizing antibodies.	Quest - Discovery Stage Research Projects	$1,143,600
Zack Jerome	University of California, Los Angeles	Human Embryonic Stem Cell Therapeutic Strategies to Target HIV Disease	Comprehensive Grant	$2,401,903
William Kennedy	Excision BioTherapeutics	Phase 1 Clinical research program for functional cure of HIV with EBT-101, in-vivo gene therapy	Clinical Trial Stage Projects	$6,852,486
Geoff Symonds	Calimmune, Inc.	GENE-MODIFIED HEMATOPOIETIC STEM/PROGENITOR CELL BASED THERAPY FOR HIV DISEASE	Disease Team Research I	$8,278,722
Mark Anderson	University of California, San Francisco	Stem cell differentiation to thymic epithelium for inducing tolerance to stem cells	Transplantation Immunology	$1,314,089
Mehrdad Abedi	University of California, Davis	Stem Cell Gene Therapy for HIV in AIDS Lymphoma Patients	Disease Team Therapy Planning I	$66,880
Zack Jerome	University of California, Los Angeles	Stem Cell Programming With Chimeric Antigen Receptors to Eradicate HIV Infection	Early Translational IV	$4,925,166
Irvin Chen	University of California, Los Angeles	Development of a humanized mouse model for testing anti-HIV HSPC gene therapy strategies in HIV-1 infected mice.	Early Translational from Disease Team Conversion	$1,505,000
Mark Anderson	University of California, San Francisco	Generation of a functional thymus to induce immune tolerance to stem cell derivatives	Basic Biology V	$1,191,000
John Zaia	City of Hope, Beckman Research Institute	A Phase I, Open-Label Study To Assess The Safety, Feasibility and Engraftment of Zinc Finger Nucleases (ZFN) CCR5 Modified Autologous CD34+ Hematopoietic Stem/Progenitor Cells (SB-728MR-HSPC) with Escalating Doses of Busulfan In HIV-1 (R5) Infected Sub...	Strategic Partnership III Track A	$5,583,438
Paula Cannon	University of Southern California	Site-specific gene editing in hematopoietic stem cells as an anti-HIV therapy	Tools and Technologies III	$1,495,665
Mehrdad Abedi	University of California, Davis	Stem Cell Gene Therapy for HIV Mediated by Lentivector Transduced, Pre-selected CD34+ Cells in AIDS lymphoma patients	Clinical Trial Stage Projects	$8,414,265
David Baltimore	California Institute of Technology	Immunotherapy for HIV infection using engineered hematopoietic stem/progenitor cells	Quest - Discovery Stage Research Projects	$1,569,193
Irvin Chen	University of California, Los Angeles	Stem Cells: A New Avenue of HIV Research and New Approaches to HIV Treatment	Conference	$24,456
				Total: $87,407,103.00