Award Announcement

amfAR Awards New Funding for Gene Therapy Study Aimed at Curing HIV

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Grant supports next phase of three-pronged approach to gene therapy-based cure

NEW YORK, Nov. 6, 2018 --- amfAR, The Foundation for AIDS Research, has awarded $800,000 in new funding to researchers developing an ambitious gene therapy-based approach to curing HIV. The award launches a critical new phase in a study initiated in 2017 with $2.3 million in grants awarded to seven teams of researchers. Six of the teams will move forward with the next phase of the project.

amfAR has forged a unique collaboration among world leaders in gene therapy that began with a think tank in 2016. The amfAR-led meeting gave rise to a plan to create the first combination intervention that will simultaneously address the main barriers to a cure. In a three-pronged attack on the HIV reservoir, the researchers will employ broadly neutralizing antibodies, CAR stem cells—cells genetically reprogrammed to recognize and attack disease cells—and molecular scissors targeting the virus.  

“This is an ambitious and complex project with very exciting potential,” said amfAR Chief Executive Officer Kevin Robert Frost. “It’s a carefully constructed strategy that involves some of the most talented and innovative scientists in the field. We think it holds great promise for developing the scientific basis of a cure by the end of 2020, which is the aim of our Countdown to a Cure for AIDS initiative.”

The researchers will test an approach that combines CAR stem cells that secrete broadly neutralizing antibodies, together with an enzyme (Brec1) that targets HIV DNA in the cell it has infected (while leaving other DNA intact), and long-term secretion of a broadly neutralizing antibody from the liver. The goal is to 1) induce CAR stem cells to kill reservoir cells; 2) to express two different antibodies to neutralize virions (virus that exists outside of cells) in the blood and tissues, and; 3) to use Brec1 to remove the provirus (virus that has been integrated into a cell’s DNA) from infected cells.

The investigators are: Hildegard Büning, Ph.D. (co-principal investigator, molecular biologist, Hannover Medical School, Hannover, Germany), who was recently named president of the European Society of Gene and Cell Therapy;  Keith Jerome, M.D., Ph.D. (co-principal investigator, virologist, University of Washington, Seattle); Hans-Peter Kiem, M.D., Ph.D. (transplantation biologist, Fred Hutchinson Cancer Research Center, Seattle); Scott Kitchen, Ph.D. (molecular biologist, UCLA, Los Angeles); Drew Weissman, M.D., Ph.D. (Immunologist, University of Pennsylvania, Philadelphia); and Richard Wyatt, Ph.D. (immunologist, The Scripps Research Institute, La Jolla).

Timothy Brown (the "Berlin patient") remains the only person known to have been cured of HIV. Brown received a stem cell transplant from a donor with a rare genetic mutation known as CCR5-delta 32, which conferred resistance to HIV infection. Ten years later, he remains free of the virus. 

“While Timothy Brown’s cure was the result of a very different gene therapy intervention, it nonetheless points to the enormous potential of gene therapy as a means of eliminating HIV,” said Dr. Rowena Johnston, amfAR Vice President and Director of Research. “We realize that delivering a gene therapy intervention to HIV-infected people around the world will be a considerable challenge. Part of the mandate of this group of researchers is to design a combination gene therapy intervention that could be effectively delivered by a single injection.”

The grant was supported in part by the Bill and Melinda Gates Foundation.

 About amfAR

amfAR, The Foundation for AIDS Research, is one of the world’s leading nonprofit organizations dedicated to the support of AIDS research, HIV prevention, treatment education, and advocacy.  Since 1985, amfAR has invested more than $517 million in its programs and has awarded more than 3,300 grants to research teams worldwide.

amfAR Renews Investment in Bioengineering Approaches to Curing HIV

amfAR, The Foundation for AIDS Research, today announced a pair of research grants that renew its support for innovative approaches to HIV cure research. Totaling nearly $1 million, the Investment grants will allow two collaborative teams of HIV researchers and bioengineers to embark on a second phase of projects initiated with amfAR funding awarded in February 2017. 

New amfAR Research Grants Advance Gene Therapy and Other Innovative Approaches to HIV Cure

More than $3.5 million awarded to researchers
aiming to overcome barriers to curing HIV
 

 

NEW YORK, NY, July 13, 2017 – amfAR, The Foundation for AIDS Research, has awarded more than $3.5 million for 13 new research grants to support innovative approaches to depleting or eliminating the persistent reservoirs of HIV not cleared by antiretroviral therapy – considered the main barrier to a cure. The grants represent the latest investments in the Foundation’s Countdown to a Cure for AIDS initiative, which is aimed at developing the scientific basis of a cure by the end of 2020. To date, amfAR has awarded Countdown grants totaling close to $42 million to support research conducted by more than 222 scientists working at 74 institutions in 10 countries around the world.

“Curing HIV is no longer a pipe dream, and the case of ‘the Berlin patient’ provides proof-of-principle that a cure is possible,” said amfAR Chief Executive Officer Kevin Robert Frost, referring to the only person known to have been cured of HIV. “However, several complex scientific challenges remain, and these new grants reflect amfAR’s determination to pursue a range of strategies to overcome them.”  

Through the amfAR Research Consortium on HIV Eradication (ARCHE), a program that fosters collaboration among teams of scientists, more than $2.3 million in grants was awarded to seven teams of researchers working on gene therapy-based approaches to curing HIV. While pharmacological and immunological approaches remain the dominant cure strategies, the Berlin patient’s cure involved a procedure that points to the promise of gene therapy.

The grantees are: Hildegard Büning, Ph.D., of Hannover Medical School in Hannover, Germany; Keith Jerome, M.D., Ph.D., of University of Washington in Seattle; Hans-Peter Kiem, M.D., F.A.C.P., of Fred Hutchinson Cancer Research Center, Seattle; Scott Kitchen, Ph.D., of University of California, Los Angeles; Yasuhiro Takeuchi, Ph.D., of University College London, United Kingdom; Drew Weissman, M.D., Ph.D., of University of Pennsylvania, Philadelphia; and Richard Wyatt, Ph.D., of The Scripps Research Institute in La Jolla, CA.

Gene therapy offers the tantalizing possibility of manipulating DNA as a means of attacking infected cells that make up the HIV reservoir, altering the susceptibility of cells to HIV infection, or enhancing the ability of the immune system to attack or block the virus. But it carries a number of risks and challenges. Scientists need to find ways to improve the efficiency of appropriately altering DNA, effectively target the correct cells, and enable the therapy to safely persist long enough to have an effect.

The researchers will pursue projects aimed at: designing and refining vectors that can accurately target the cells that make up the reservoir and regions such as the lymph nodes, where the reservoir cells tend to be concentrated; using so-called CAR T cells, which have shown remarkable promise in clearing some types of cancer, as a potential means of killing HIV-infected cells; and exploring the potential of using viral and non-viral delivery mechanisms to deliver emerging types of genetic scissors that could cut the virus out of human DNA.

In a second round of grants, amfAR awarded $1.2 million to six researchers who will explore mechanisms of HIV persistence and the potential for HIV eradication. These “Innovation” grants are designed to test and advance innovative ideas in the early stages of testing.

For instance, Andrew Badley, M.D., from the Mayo Clinic College of Medicine in Rochester, MN, will test whether ixazomib, a drug currently used to treat the blood cancer multiple myeloma, can reduce the size of the viral reservoir in the body. Joshua Schiffer, M.D., from Fred Hutchinson Cancer Research Center in Seattle, WA, will test a drug normally used to prevent organ transplant rejection for its potential to eliminate the persistent HIV reservoir.

Andrew Henderson, M.D., from Boston University School of Medicine in Boston, MA, and Fabio Romerio, Ph.D., from University of Maryland, Baltimore, MD, will both explore a cure strategy known as “block & lock,” which aims to permanently silence HIV and prevent the emergence of virus when antiretroviral therapy is stopped.

Brad Jones, Ph.D., from The George Washington University, Washington, DC, aims to develop a new class of broadly neutralizing antibodies that enable the immune system to recognize proteins not normally accessible to the body’s antibody making machinery. The goal is to increase the number of people in whom broadly neutralizing antibodies are able to find and kill HIV-infected cells.

And to better understand how Timothy Brown, “the Berlin patient,” was cured of HIV, Benjamin Burwitz, Ph.D., from Oregon Health and Science University in Portland, will explore the precise mechanisms that led to his cure by generating a monkey model lacking the protein CCR5, the primary means by which most types of HIV infect cells.

“These two rounds of grants get to the heart of the scientific challenges we face in our search for a cure,” said Dr. Rowena Johnston, amfAR’s vice president of research. “Through these projects, we will continue to forge the scientific alliances - within HIV and beyond - that we believe are our best hope for accelerating progress toward a cure.”

Click here for full descriptions of the ARCHE and Innovation grants.

 

About amfAR:

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amfAR, The Foundation for AIDS Research, is one of the world’s leading nonprofit organizations dedicated to the support of AIDS research, HIV prevention, treatment education, and the advocacy of sound AIDS-related public policy. Since 1985, amfAR has invested more than $480 million in its programs and has awarded grants to more than 3,300 research teams worldwide.

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Innovation Grants 2017

PI: Andrew Badley, MD
Mayo Clinic College of Medicine, Rochester, MN

$200,000 (#109593)
Ixazomib to reduce HIV reservoir size: Cells have a recycling mechanism that disposes of or reuses old proteins—the proteasome. If the proteasome is disrupted, these damaged proteins persist, clogging up the cell and eventually leading to cell death. Ixazomib is a drug that is currently used in multiple myeloma, a form of blood cancer. Dr. Andrew Badley proposes to conduct a clinical study to test the ability of the drug to reduce the viral reservoir, the main barrier to a cure. 

PI: Benjamin Burwitz, PhD
Oregon Health and Science University, Portland, OR
$199,948 (#109596)
Creation of CCR5 knockout Mauritian cynomolgus macaques for stem cell transplants:
The Berlin patient, the first and only patient so far to have been cured of HIV, received a stem cell transplant from a donor who was genetically resistant to HIV because the donor lacked a key HIV receptor, the protein CCR5.  The Berlin patient’s difficult medical history and complications have made it difficult to determine exactly what led to his cure: was it the stem cell transplant, the complications presented by his new immune system attacking HIV-infected cells as part of a transplant complication known as graft vs. host disease, the chemotherapy and radiation used in the transplant, or some combination of these? Dr. Benjamin Burwitz proposes to answer these questions by generating a monkey model lacking CCR5, enabling him to test the multiple hypotheses concerning the Berlin patient’s cure.

PI: Andrew Henderson, PhD
Boston University School of Medicine, Boston, MA
$200,000 (#109603)
Disabling HIV provirus by promoting chromatinization: CRISPR/Cas9, a protein complex recently discovered in bacteria, has revolutionized biology because of the flexibility and ease with which scientists can use it to target and edit DNA, cutting out unwanted pieces, including the DNA form of HIV. Dr. Andrew Henderson is proposing to use this protein complex to silence the HIV DNA in a so-called “Block & Lock” approach. Unlike “Shock & Kill”, which requires the cell to wake up from latency- a formidable challenge - “Block & Lock” would permanently silence HIV and prevent the emergence of virus when ART is stopped.

PI: Brad Jones, PhD
The George Washington University, Washington, DC
$199,998 (#109606)
HLA-E specific TCR-like Antibodies for the Universal Targeting of Persistent HIV Reservoirs: Broadly neutralizing antibodies that target the viral protein Env—the only viral protein expressed on the surface of infected cells - must circumvent the high mutation rate of Env in order to be effective. On the other hand, viral proteins present inside the cell are much less subject to mutation but are poorly accessible to our body’s antibody making machinery. Because of a newly discovered immune mechanism, scientists have now found that the internal viral proteins may be digested and displayed on the surface of cells in a molecule called HLA-E. Dr. Brad Jones proposes to engineer antibodies that will recognize the digested protein/HLA-E complex and make the cell susceptible to death by Natural Killer cells.

PI: Fabio Romerio, PhD
University of Maryland, Baltimore, MD
$199,999 (#109612)
Permanent Silencing of HIV-1 Expression through the Polycomb Repressor Complex 2 epigenetic pathway: Dr. Fabio Romerio has uncovered a unique mechanism through which HIV drives its own latency, namely by making a molecule called Ast. He proposes that Ast participates in actively preventing the viral DNA from making virus. Dr. Romerio aims to determine how Ast asserts its effect and whether it can be delivered to all HIV infected cells to permanently and specifically block viral DNA. In contrast to the curative approach “Shock & Kill”, this “Block & Lock” approach aims to silence HIV and prevent the emergence of virus when ART is stopped.

PI: Joshua Schiffer, MD
Fred Hutchinson Cancer Research Center, Seattle, WA
$200,000 (#109614)
Anti-proliferative therapy for eradication of the HIV reservoir: Antiretroviral therapy (ART) controls viral load because the virus is prevented from infecting new cells. However, the reservoir persists even under ART through mechanisms that are still being uncovered. One possibility is that normal cell division of latent HIV infected cells maintains the reservoir even in the absence of viral replication. Dr. Joshua Schiffer aims to determine if CellCept, a drug that reduces cell replication – normally used to prevent organ transplant rejection - can also eliminate the persistence of the reservoir. His clinical trial will span 2 years, after which participants will discontinue their ART and determine whether the curative intervention worked.

ARCHE Gene Therapy Grants

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July 2017

Hildegard Büning, Ph.D. – principal investigator
Hannover Medical School, Hannover, Germany
$386,578 (109570)
Vector-mediated in vivo targeting of HIV reservoir cells or provirus elimination: To maximize safety of gene therapy, methods to specifically target reservoir cells are required. The HIV reservoir consists mainly of CD4+ T cells, with certain subsets more commonly harboring latent HIV. Dr. Büning plans to design an adeno-associated viral vector that specifically targets one of these main subsets, the central memory T cells. The vector will be designed to carry a gene editing tool called Brec1, previously shown to suppress HIV. One reported advantage of Brec1 over other gene editing tools is the apparent lack of off-target effects. 

Keith Jerome, M.D., Ph.D. – principal investigator
University of Washington, Seattle, WA
$399,955 (109575)
Subcutaneous administration of DARPin-modified adeno-associated virus vectors for selective targeting of CD4+ T cells: Curing a diffuse disease such as HIV, as opposed to a localized tissue-specific disease, requires a way to target the gene therapy to the target cells of interest, which in HIV are dispersed throughout the body. Dr. Jerome plans to use adeno-associated viral virus vectors engineered to utilize small, antibody-like  proteins to target the vectors and their gene-editing cargo directly to CD4+ T cells, which comprise the majority of the HIV reservoir. He will also experiment with ways of infusing the vectors such that they preferentially reach the lymph nodes, where most reservoir cells are found.

Hans-Peter Kiem, M.D., F.A.C.P. – principal investigator
Fred Hutchinson Cancer Research Center, Seattle, WA
$200,000 (109608)
Engineering blood cells to produce broadly neutralizing anti-HIV antibodies: Antibodies have been the focus of increasing optimism in the HIV cure research field due to their ability to not only neutralize virus particles, but also to target and help kill infected cells. Dr. Kiem plans to genetically modify immune system progenitor cells to serve as a constant source of antibodies. By engineering cells that will differentiate into a variety of types of immune cells, Dr. Kiem hopes that the progeny cells will migrate to various parts of the body, including lymph nodes and brain known to be important reservoirs of HIV.

Scott Kitchen, Ph.D. – principal investigator
University of California, Los Angeles, Los Angeles, CA
$400,000 (109577)
Optimized efficacy and persistence of engineered HIV-specific cellular immunity: Chimeric antigen receptor (CAR) cells have shown remarkable promise in their ability to clear some cancers in patients, and additionally have shown potential in HIV cure. Dr. Kitchen plans to improve the ability of CAR cells to kill HIV-infected cells by increasing their ability to detect the appropriate target cells and prolonging their survival. He also plans to engineer improvements to minimize the loss of CAR cells to attack by the immune system, and to design a mechanism to “switch off” CAR cells should they become unsafe or are no longer needed.

Yasuhiro Takeuchi, Ph.D. – principal investigator
University College London, London, United Kingdom
$360,034 (109584)
LentiStim: Mass production of lentiviral vectors for in vivo gene delivery: Curing HIV by gene therapy may require long-term persistence of the gene editing tools delivered by lentiviral vectors, which are closely related to HIV. Because the reservoir that harbors persistent HIV consists almost entirely of resting cells, such vectors cannot gain entry into the cells to deliver their cargo. Dr. Takeuchi plans to modify lentiviral vectors with a cocktail of stimulatory molecules that induce an optimal level of activation in the target cell, thus allowing entry of the vector. The effectiveness of lentiviral vectors is also plagued by immune responses raised against the vector, so the team will produce vectors that are resistant to destruction by the immune system.

Drew Weissman, M.D., Ph.D. – principal investigator
University of Pennsylvania, Philadelphia, PA
$400,000 (109587)
Targeting of nucleic acid therapeutics to cure HIV: Gene therapy approaches to cure HIV include efforts to cut the virus out of the human DNA, or to imbue the human host cells with characteristics that protect them from infection. Dr. Weissman plans to employ nucleic acid therapeutics as the tools to edit DNA to achieve either or both of these goals. One advantage of nucleic acid therapeutics is the ability to administer them repeatedly without raising an immune response that would destroy them. He plans to optimize their delivery to the appropriate cells by packaging them inside lipid nanoparticles that can be engineered with surface particles that guide them to specific targets.

Richard Wyatt, Ph.D. – principal investigator
The Scripps Research Institute, La Jolla, CA
$199,362 (109618)
Vector-mediated in vivo targeting of HIV reservoir cells or provirus elimination: Chimeric antigen receptor (CAR) cells have shown remarkable promise in their ability to clear some cancers in patients, and additionally have shown potential in HIV cure. One advantage is their ability to overcome a cancer or virus-infected cell’s ability to hide from the immune system. Dr. Wyatt plans to generate CAR T cells with the ability to kill HIV infected cells just as they begin to produce virus. Additionally, the CAR T cells will be engineered to produce antibodies that can neutralize any virus that is produced.

New amfAR Grants Enlist Help of Bioengineers to Overcome Obstacles to Curing HIV

New amfAR Grants Enlist Help of Bioengineers to Overcome Obstacles to Curing HIV

In a novel approach to conquering HIV, amfAR, The Foundation for AIDS Research, is pairing HIV researchers with bioengineers to address the main barrier to a cure for HIV: the persistent reservoirs of virus not cleared by antiretroviral therapy. A new round of Investment grants, totaling $1.2 million, will support six new research projects aimed at bringing to bear highly advanced technologies that until recently might have belonged in the pages of a science fiction novel.   

New amfAR Grants Spur Innovative HIV Cure Research Collaborations

NEW YORK, Jan. 25, 2016 --- In a move that adds extraordinary new dimensions to the field of HIV cure research, amfAR, The Foundation for AIDS Research, has recruited the expertise of a world-renowned physicist and a leading polymer chemist. The Foundation has awarded $1 million each over four years to Harvard physicist Dr. David Weitz and bioengineer and polymer scientist Dr. Alexander Zelikin of Aarhus University in Denmark. The two will bring their expertise to bear in the effort to eradicate the viral reservoir that is considered the principal barrier to curing HIV. 

The new awards are the latest to be funded by amfAR through its $100 million Countdown to a Cure for AIDS initiative, whose goal is to develop the scientific basis for a cure by 2020. The grants were aimed specifically at recruiting the expertise of scientists working outside the field of HIV in areas that could directly inform efforts to cure HIV. Drs. Weitz and Zelikin will collaborate with leading AIDS researchers Dr. Bruce Walker at Harvard and Dr. Martin Tolstrup at Aarhus University, respectively. 

“Research to find a cure for AIDS has evolved from a process of discovery to a challenge of technology,” said amfAR Chief Executive Officer Kevin Robert Frost. “And recent technological advances have brought with them some exciting opportunities for the cross-pollination of ideas and for adapting cutting-edge technologies to the field of HIV cure research.”

Dr. Weitz, who is the Mallinckrodt Professor of Physics and Applied Physics at the John A. Paulson School of Engineering and Applied Sciences at Harvard University, is a world leader in the field of microfluidics. This cutting-edge scientific field, which involves the manipulation of minuscule volumes of fluid using state-of-the art devices and processes, has already revolutionized a wide array of scientific fields. 

Dr. Weitz has developed a technique that uses fluid mechanics to specifically isolate the most effective killer T cells from those that are less potent. He proposes to isolate these cells—a critical weapon of the immune system against virally infected cells—from patient samples, clone them in a petri dish, and use a mouse model to test whether the reinjection of these killer cells can lead to a functional cure of HIV.  

Dr. Zelikin is an expert in prodrugs—temporarily inactive drugs that become active only when instructed by a second stimulus—which he plans to use to eliminate the HIV reservoir. The project will design a two-component cocktail. One prodrug will be developed to gently reawaken the latent HIV using a drug that Dr. Martin Tolstrup, a virologist and HIV expert, has shown to be effective in patients.  The second prodrug will be designed to specifically initiate the killing of virally infected cells.  Acting in tandem, the two prodrugs administered together are poised to specifically activate the latent viral reservoir and kill the cells harboring HIV.

“The ‘outside the box’ approaches proposed by Drs. Weitz and Zelikin will both expand and invigorate the field of HIV cure research,” said Rowena Johnston, Ph.D., amfAR Vice President and director of research. “We are tremendously excited to be supporting these studies, each of which holds enormous potential for depleting, and perhaps even clearing, the persistent reservoir of HIV.”

Investment Grants 2016  

PI: David Weitz, PhD
Collaborating HIV Scientist: Bruce Walker, MD
Harvard University
$977,114
Eradicating the HIV reservoir: Using microfluidics to exploit killer T cells
Killer T cells are part of the immune system’s arsenal against virally infected cells. Despite their name, not all members of this group are equally effective in killing HIV-infected cells. To date, efforts to isolate killer T cells with the most potent killing potential have been too broad to deliver the results needed to make strides against disease. This problem is being solved by Dr. David Weitz, a physicist and world recognized leader in microfluidics. Dr. Weitz has harnessed his years of cutting-edge contributions of applied physics in biology, by developing a machine that uses fluid mechanics to specifically isolate the best, most effective killer T cells from those that are less potent. He proposes to isolate these killers from patient samples, clone them in a petri dish, and use a humanized mouse model to test whether the reinjection of these killer cells can lead to a functional cure of HIV. His collaboration with Dr. Bruce Walker, an HIV pioneer whose studies have defined the field of HIV immunology, will ensure that this novel, microfluidic-based approach will test the necessary elements that could lead to T cell therapy in humans.

PI: Alexander Zelikin, PhD
Collaborating HIV Scientist: Martin Tolstrup, PhD
Aarhus University, Aarhus, Denmark
$962,510
Tandem latency reversal and suicide prodrugs to eliminate HIV reservoirs
A major obstacle to HIV eradication is the presence of a latent viral reservoir that is established soon after infection. This cryptic reservoir, responsible for the viral rebound once the patient is off antiretroviral therapy, is difficult to locate and the body’s immune system is unable to clear the viral reservoir. An approach to circumvent these issues is offered here by a bioengineer and polymer chemist, Dr. Alexander Zelikin. The project builds on Dr. Zelikin’s expertise in developing prodrugs—labile drugs that become active when instructed by a specific stimulus. The project will design a two-component cocktail. One prodrug will be developed to gently reawaken the latent HIV using a drug that Dr. Martin Tolstrup, a virologist and HIV expert, has shown to be effective in patients.  The second prodrug will be designed to specifically initiate the killing of virally infected cells.  Acting in tandem, the two prodrugs administered together are poised to activate the latent viral reservoir and kill the cells harboring HIV.

 

About amfAR

amfAR, The Foundation for AIDS Research, is one of the world’s leading nonprofit organizations dedicated to the support of AIDS research, HIV prevention, treatment education, and the advocacy of sound AIDS-related public policy. Since 1985, amfAR has invested $450 million in its programs and has awarded grants to more than 3,300 research teams worldwide. Learn more about amfAR at www.amfar.org.

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New amfAR Awards Accelerate Research Towards HIV Cure

NEW YORK, Oct. 22, 2015 --- amfAR, The Foundation for AIDS Research, on Thursday announced a new round of research grants totaling more than $1.4 million. The vast majority of the funding will support cure-focused research projects.

Renewal funding of $850,000 will go to a consortium of European researchers that aims to replicate the case of the “Berlin patient,” the first and only person known to have been cured of HIV. Diagnosed with leukemia, the patient was given a stem cell transplant with a twist: The cells he received were taken from a donor with a rare genetic mutation conferring resistance to HIV infection. He remains virus-free.

Working within the amfAR Research Consortium on HIV Eradication (ARCHE), a research program launched in 2010 to explore potential strategies for eliminating HIV, the scientists will study the outcomes of HIV patients who undergo different types of stem cell transplants. Led by Javier Martinez-Picado, Ph.D., of IrsiCaixa in Spain and Annemarie Wensing, M.D., Ph.D., of University Medical Center Utrecht in the Netherlands, the consortium has already identified a group of patients who have undergone transplants, and continues to monitor their progress in the hope of generating new knowledge that can inform more widely applicable interventions.

“We’re very excited to continue our support of the scientists in the European consortium,” said amfAR Chief Executive Officer Kevin Robert Frost. “They have made good progress since we began supporting their work last year, and they have real potential for significantly advancing the field of HIV cure research.” 

In addition, amfAR awarded a total of $600,000 to four promising young scientists who will each receive $150,000 over two years. These Mathilde Krim Fellowships in Basic Biomedical Research, named in honor of amfAR’s Founding Chairman Dr. Mathilde Krim, are awarded annually to nurture new talent within the HIV/AIDS research field.

Two of the Fellows will study aspects of the reservoirs of latent virus that are the main obstacle to eradicating HIV.

Luis Agosto, Ph.D., of Boston Medical Center, will explore a mechanism that involves the covert shuttling of HIV between cells, which could be an important factor by which the virus evades the immune response and thus may maintain the viral reservoir. Liang Shan, Ph.D., of Yale University in New Haven, CT, will use a humanized mouse model to test the efficacy of latency reversing drugs, studying their ability to reactivate HIV so that the immune system can kill those cells that harbor the virus.

Louise Scharf, Ph.D., at the California Institute of Technology in Pasadena, CA, will study the molecular structure of broadly neutralizing antibodies isolated from two HIV-infected patients to better understand how these powerful antibodies can help in the development of a vaccine against HIV.

And Amit Sharma, Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle, WA, will explore how Rhesus macaques can be better utilized as an animal model in vaccine studies. Since the macaques are not susceptible to HIV and therefore cannot be used to study HIV specific antibodies, scientists have made viruses that are part SIV (the simian version of HIV) and part HIV, called SHIVs. However, not all SHIVs replicate efficiently, which limits their usefulness in the lab. Dr. Sharma is looking into what restricts the replication of some SHIVs but not others. His findings could help accelerate the field of vaccine research.

“The Krim Fellows are doing work that could produce major contributions to HIV/AIDS cure and vaccine research,” said amfAR Vice President and Director of Research Dr. Rowena Johnston. “Their projects are exciting and innovative, and we look forward to closely following their progress.”

About amfAR

amfAR, The Foundation for AIDS Research, is one of the world’s leading nonprofit organizations dedicated to the support of AIDS research, HIV prevention, treatment education, and the advocacy of sound AIDS-related public policy. Since 1985, amfAR has invested $415 million in its programs and has awarded grants to more than 3,300 research teams worldwide. Learn more about amfAR at www.amfar.org.

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New amfAR Grants Accelerate Research Efforts to Eradicate HIV

Three research teams awarded $2 million each over four years to conduct basic, animal and clinical studies

NEW YORK, July 21, 2015 --- amfAR, The Foundation for AIDS Research, announced that three research teams have been awarded $2 million each to pursue a range of strategies aimed at curing HIV. The new grants are part of amfAR’s $100M Countdown to a Cure initiative, launched last year with the aim of discovering the scientific basis for a cure by 2020. Each project is designed to tackle the major impediment to curing HIV, namely the persistence of the virus despite anti-HIV drugs. 

"At $2 million each, these new grants represent the continued expansion of amfAR’s investments in research to find a cure for AIDS, and they are among the largest grants we have ever awarded.  They are a reflection of our optimism around cure research and our collective determination to invest $100 million over the next five years in order to develop the scientific basis of a cure for this disease," said amfAR Chief Executive Officer Kevin Robert Frost. 

A team of researchers led by Dan Barouch, M.D., Ph.D., of Beth Israel Deaconess Medical Center in Boston, Massachusetts, will investigate the ability of combinations of antibodies to specifically kill latently infected cells in the lab, in monkeys, and then in people. The researchers will test two promising antibodies alone and together, in combination with a newly described drug that can “shock” the virus out of latently infected cells and possibly enhance the ability of the antibodies to locate the infected cells.

Timothy Henrich, M.D., of the University of California, San Francisco, and his colleagues will pursue a novel intervention aimed at restoring normal immune function in people with HIV. The team will test whether the transplant drug, sirolimus, can increase the activity of beneficial components of the immune system while suppressing detrimental activity of other components. The team will thoroughly assess the drug’s activities before moving on to test the drug on persistent HIV reservoirs in people. 

Using an approach that has already proved successful in cancer therapy, Sharon Lewin, FRACP, Ph.D., of the University of Melbourne, Australia, will explore whether drugs that block so-called immune checkpoints can also be effective against HIV. Researchers theorize that the immune system cannot eliminate infected cells because of immune checkpoints, a set of mechanisms that limit the duration of an immune response so that the immune system does not become exhausted.  Dr. Lewin and her team will test two drugs, alone and together, for their ability to reverse immune exhaustion and restore the ability of the immune system to eliminate infected cells. 

“These four-year grants are a departure for amfAR and an important pillar of our cure research strategy,” said Rowena Johnston, Ph.D., amfAR vice president and director of research.  “They allow teams of leading researchers to take their ideas across the research continuum—from lab studies to human trials. We’ll be following their progress with great interest.”

amfAR Announces $2.4 Million in New HIV Cure Research Grants

It has been six years since the first case of a cure was reported in an HIV-positive man with leukemia who received a stem cell transplant from a donor with a rare genetic mutation conferring resistance to HIV infection. The case of “the Berlin patient” raised as many questions as it answered, and it dramatically changed the trajectory  of HIV/AIDS research.

amfAR Announces New Round of Cure-Focused Research Grants

The principal barrier to curing HIV is the reservoirs of infected cells that cannot be cleared by the immune system. Adding to the multiple ways HIV shields itself from attack is the recent discovery of an “invisibility cloak.” But what if we could uncloak the virus so that it can be seen and targeted by the immune system? 

amfAR Intensifies Efforts to Find a Cure for HIV

Shortly after launching the “Countdown to a Cure for HIV/AIDS,” a research initiative aimed at finding a broadly applicable cure for HIV by 2020, amfAR, The Foundation for AIDS Research on Wednesday announced that it has awarded 12 grants to researchers in the United States and around the world to pursue cure-focused HIV research. The new grants total more than $2.15 million...