Infusion of Funding for amfAR HIV Cure Consortium
New grants enable four teams of leading researchers to build on research momentum
in collaborative effort to eradicate HIV
NEW YORK, July 18, 2013 - As part of its mission to accelerate promising research focused on finding a
cure for HIV/AIDS, amfAR, The Foundation for AIDS Research, on Wednesday announced
a new round of grants through its amfAR Research Consortium on HIV Eradication (ARCHE) program. Totaling more than $1.4 million,
the ARCHE grants will support four teams of scientists working at leading research institutions around the world.
"Through ARCHE, amfAR leverages the expertise and innovation of distinguished scientists from across the globe to advance
cure-focused research," said amfAR CEO Kevin Robert Frost. "Some of the most important recent advances in HIV research are the result
of strategic collaborations among amfAR-funded scientists and are a testament to the success of our cooperative approach to research."
Earlier this year, ARCHE grantees Dr. Deborah Persaud of Johns Hopkins University and Dr. Katherine Luzuriaga of the University of
Massachusetts described
the case of the first child to be cured of HIV; an amfAR grant enabled the researchers to perform highly sophisticated tests that
confirmed the cure. And in July, another ARCHE grantee, Dr. Timothy Henrich of Harvard Medical School and Brigham and Women's
Hospital in Boston, reported on the case of two HIV-positive
patients who show no trace of virus following stem-cell transplants.
"The ARCHE program has enabled us to gain invaluable insights into how we can potentially eradicate HIV," said Dr. Rowena
Johnston, amfAR vice president and director of research. "As we enter our fourth year of ARCHE funding, we are excited at the prospect
of generating further discoveries that could ultimately bring us the cure that we so urgently need."
This year's grants will enable researchers from the United States, United Kingdom, France, Thailand, and Australia to
collaborate on studies exploring potential strategies for eliminating HIV infection. One study, led by Dr. Eric Arts of Case Western
Reserve University in Cleveland, Ohio, aims to develop and test a vaccine-like HIV treatment specific to each patient's virus.
Unlike other approaches toward an HIV cure that focus on inducing cell changes in all cells that are vulnerable to HIV
infection, this treatment specifically targets the infected cells lying dormant in the viral reservoir. Dr. Arts and
Dr. Yong Gao from Case Western will work with Drs. Robin Shattock, Sarah Fidler, and Caroline Foster of Imperial
College London to study the treatment's effectiveness.
In another study, a team led by Dr. Nicolas Chomont of the Vaccine and Gene Therapy Institute in Port St. Lucie, Florida,
will study HIV persistence in T-cell subsets during antiretroviral therapy. Specifically, they will investigate the subsets of CD4+ T
memory cells - the cells where the HIV reservoir mainly resides - and the roles they may play as a potential target for a cure.
Dr. Chomont will work in collaboration with three-time ARCHE grantees Dr. Sarah Palmer of the University of Sydney in
Australia and Dr. Steven Deeks of the University of California, San Francisco; Dr. Jintanat Ananworanich from SEARCH
in Bangkok, Thailand; and Dr. Asier Saez-Cirion of Institut Pasteur in Paris, France.
Researchers from University of California, Los Angeles (UCLA) and University of Washington led by Dr. Scott Kitchen of UCLA
will explore gene therapy using stem cells as a potential cure. Joined by Drs. Jerome Zack and Irvin Chen from UCLA and Dr. Hans-Peter
Kiem of University of Washington, the researchers plan to modify stem cells so that they bind directly to HIV. These modified cells
would then mature into a specific type of immune cells that can kill infected cells. The researchers theorize that the treatment
will help to reduce the size of, and perhaps even eradicate, the viral reservoir.
The fourth study will be conducted by four-time ARCHE grantee Dr. Robert Siliciano of Johns Hopkins University in Baltimore.
Dr. Siliciano will build on his recent finding that as many as 40 to 50-fold more cells may harbor viruses but are not counted in size
estimate of the viral reservoir. Dr. Siliciano will focus on identifying those cells and their properties, and determining how the
viruses may be induced out of these infected cells so they can be targeted by antiretroviral therapy.
ARCHE-funded research teams and their projects are as follows:
Case Western Reserve University, Cleveland, OH
Eric Arts, Ph.D. - principal investigator
Yong Gao, M.D., Ph.D. - collaborating investigator (CWRU)
Robin Shattock, Ph.D. - collaborating investigator (Imperial College London)
Sarah Fidler, M.D. - collaborating investigator (Imperial College London)
Caroline Foster, M.D. - collaborating investigator (Imperial College London)
$349,964
Activation of latent HIV using an autologous HIV vector: Pharmacological approaches currently being
investigated for their potential to cure HIV do not specifically target infected cells, but rather induce changes in cells globally
throughout the body. In order to home in more specifically on infected cells that represent the HIV reservoir, Dr. Arts and
colleagues plan to make and test a vaccine-like product specific to each patient's virus. They hypothesize that those cells
that quiescently harbor HIV during antiretroviral therapy will be specifically induced to respond to the vaccine-like
product, resulting in their death. They will test their product in cells taken from adults and pediatric patients
treated during acute or chronic infection.
University of California, Los Angeles, Los Angeles, CA
Scott Kitchen, Ph.D. - principal investigator
Jerome Zack, Ph.D. - collaborating investigator (UCLA)
Irvin Chen, Ph.D. - collaborating investigator (UCLA)
Hans-Peter Kiem, M.D., F.A.C.P. - collaborating investigator (U Washington)
$300,000
Identifying and targeting HIV persistence in T cell subsets during ART: The HIV reservoir - that fraction
of the virus that persists despite taking antiretroviral therapy - exists largely in CD4+ T memory cells. Emerging evidence suggests that
the proportion of the reservoir that resides in different subsets of CD4+ T cells - central, transitional, effector, naïve, memory
stem cells - may vary between patients. The subsets of CD4+ T cells in which the reservoir predominates in turn can influence the size
of the total reservoir. Dr. Chomont and colleagues will investigate which subsets constitute the major fraction of the reservoir and
whether this changes over the course of the infection or with the stage of infection at which antiretroviral therapy is initiated.
Understanding the dynamics of the reservoir may shed light on whether strategies to directly target various subsets of CD4+ T
cells may be a productive strategy to cure HIV.
University of California, Los Angeles, Los Angeles, CA
Scott Kitchen, Ph.D. - principal investigator
Jerome Zack, Ph.D. - collaborating investigator (UCLA)
Irvin Chen, Ph.D. - collaborating investigator (UCLA)
Hans-Peter Kiem, M.D., F.A.C.P. - collaborating investigator (U Washington)
$300,000
Programming stem cells with a chimeric antigen receptor to eradicate HIV: Researchers seeking to cure
HIV via gene therapy are particularly interested in modifying stem cells, as they have the potential to persist for the lifetime of
the patient and can mature into all the different kinds of immune cells. Dr. Kitchen and his colleagues plan to modify stem cells
such that they bind directly with HIV. Once this contact has been made, a signal inside the modified cells will result in the
maturation of those cells into an immune effector cell with the capacity to kill infected cells. They hypothesize that the
generation of such effector cells will reduce the size of the reservoir and perhaps help to eradicate it. They will test
the product in monkeys.
Johns Hopkins University, Baltimore, MD
Robert Siliciano, M.D., Ph.D. - principal investigator
$180,000
Evaluating the threat posed by intact, non-induced proviruses: One of the challenges of curing HIV
infection is understanding the scale and nature of the reservoir of virus that persists despite antiretroviral therapy. Currently,
the best estimates place the size of the reservoir at roughly one per million resting CD4 T cells, deduced by inducing viruses
out of resting T cells. Using amfAR ARCHE funding, Dr. Siliciano has recently discovered that as many as 40-50 fold more cells
may harbor viruses that cannot be easily induced, and are thus not usually counted in estimates of the size of the reservoir.
He plans to further characterize those cells that harbor non-induced proviruses that appear otherwise intact, and to
determine the conditions under which these viruses can be induced out of the infected cells and this targeted by antiretroviral therapy.
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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 more than $366 million in its programs and has awarded grants to more than 2,000 research teams worldwide. For
more information, please visit www.amfar.org
"Reproduced with permission - amfAR, The Foundation for AIDS Research"
amfAR, The Foundation for AIDS Research
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