For Immediate Release
AnnMari Shannahan, VP Public Information
NEW YORK (February 14, 2013)—amfAR, The Foundation for AIDS Research on Thursday announced eight new grants totaling more than $1.4 million to leading researchers from around the world who are working on a variety of cutting-edge, cure-focused studies. This round of grants was supported in part by the Foundation for AIDS and Immune Research (FAIR).
See below for full descriptions of the new research projects
To leverage research resources already in place, two projects will provide additional analysis of ongoing clinical trials. One of these trials is examining a pharmacological approach to curing HIV, while the other is exploring gene therapy. In each case, the investigators—Drs. Lars Ostergaard and Rafick-Pierre Sékaly, respectively—will gather additional data and conduct analyses that will broaden our knowledge in the context of the trials.
“Investing wisely in research sometimes means capitalizing on and strengthening opportunities that already exist,” said amfAR Vice President and Director of Research Rowena Johnston, Ph.D. “This round of funding enables amfAR to widen the net of new research ideas and to deepen our understanding of ongoing research projects.”
Another funded project, led by Dr. Satish Pillai at the University of California, San Francisco, will examine how an unusual genetic mutation—CCR5-delta32—may enhance the curability of HIV. He will measure the amount of virus that persists in patients with or without this mutation. His hypothesis derives from the observation that the first person known to have been cured of HIV, the “Berlin patient,” as well as two more patients who may also have been cured, all have this mutation. Several months ago, amfAR funded a research project, led by Dr. Timothy Henrich of Brigham and Women’s Hospital, to characterize more fully the HIV status of the latter two patients.
“Whether our funded researchers are working with real-time clinical trial results or building on concurrent research being conducted by amfAR-funded scientists, one thing is clear: We’re only going to find a cure for HIV if we continue to invest in research,” said amfAR CEO Kevin Robert Frost.
More than 87 percent of amfAR’s research grants are dedicated to cure-specific projects around the world.
“We’re only going to end this epidemic through smart investments, and we believe cure research is one of the smartest,” Frost said. “If we can continue to marshal the political and financial will to end AIDS, we believe we will do it in our lifetime.”
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.
Full list of amfAR research grants announced February 8, 2012:
Christian Brander, Ph.D.
Irsicaixa AIDS Research Institute, Badalona, Spain
Immune correlates of viral rebound after therapeutic HIV vaccination: Although the immune system can greatly reduce levels of the virus after infection, it cannot maintain this control indefinitely. Therapeutic vaccines, which are currently being designed and tested, may enable patients to stop taking antiretroviral therapy (ART) without progressing to disease. Dr. Brander and his colleagues plan to closely monitor changes in immune function after subjects who are currently enrolled in a therapeutic vaccine clinical trial stop taking their ART. Their findings will help guide the design of more effective therapeutic vaccines and may also enable researchers to predict which individuals will respond best in future such trials. Therapeutic vaccines may one day play an important role in a functional cure for HIV.
Sara Gianella Weibel, M.D.
Veterans Medical Research Foundation, San Diego, CA
Impact of CMV replication on HIV latent reservoir: When additional infections are present, they can increase the level of immune activation and adversely affect the course of HIV disease. One type of infection, cytomegalovirus (CMV), is very common in the semen of men who have sex with men, and may fuel the replication and persistence of HIV because of heightened immune activation. Dr. Gianella Weibel plans to determine whether CMV infection ultimately increases the ability of HIV to persist at greater levels, even when patients are taking antiretroviral therapy (ART), by studying a cohort of HIV-infected men who started ART early in infection. Her findings will help determine whether additional measures will need to be taken to cure HIV in people who are also infected with CMV.
James Mullins, Ph.D.
University of Washington, Seattle, WA
Sorted bead sequencing to accurately assess HIV in reservoirs: Dr. Mullins plans to take advantage of two resources he has developed to answer a critical question in HIV cure research, namely where in the body reservoirs of virus reside. These reservoirs of latent virus cannot be targeted by antiretroviral therapy (ART) because the virus is not undergoing replication. He will use sorted bead sequencing, a cost- and labor-saving technology developed by him and his colleagues, to isolate individual viruses and to genetically characterize them. The findings he will generate will help scientists better understand which tissues most frequently harbor virus that is capable of replicating if patients stop taking ART, and how those viruses populate and re-seed infection in other areas of the body. Understanding the location of such reservoirs is a critical step towards developing a cure for HIV.
Lars Ostergaard, M.D., Ph.D.
Aarhus University Hospital, Aarhus, Denmark
HIV-1 cellular immunity during serial and repetitive panobinostat dosing: Once treatment with antiretroviral therapy (ART) is stopped, high levels of HIV-1 replication recur, indicating that currently available HIV drugs are insufficient to cure HIV-1. The cells in which HIV-1 “hide” during ART can be unmasked by certain classes of drugs, one of which is histone deacetylase inhibitors (HDACi). Once the virus is unmasked, it can be made subject to immune mediated killing. However, whether HDACi also enhance immune mediated killing of infected cells in humans remains unknown. Dr. Ostergaard and his colleagues propose to investigate whether cyclic and repetitive dosing of panobinostat, a potent HDACi, may facilitate immune killing of HIV-1 infected cells. They will analyze immunity to assess whether the patients’ own immune cells can decrease the persistent reservoir of virus during an ongoing clinical trial.
Satish Pillai, Ph.D.
University of California, San Francisco, San Francisco, CA
Effect of CCR5-delta32 heterozygosity on the HIV-1 reservoir: There has been one confirmed case, and two more recent reports, of an HIV cure. All three of these individuals had a somewhat unusual genetic mutation known as CCR5-delta32, suggesting that this mutation may enhance the curability of HIV-1 disease. Dr. Pillai and colleagues will address this hypothesis by collecting blood and tissue specimens from a large population of HIV-1-infected individuals, some of whom carry the CCR5-delta32 mutation. They will apply cutting-edge laboratory techniques to compare the size, composition and decay of the HIV-1 latent reservoir in individuals or without the mutation. Their study should yield biological insights that will help in designing effective curative strategies for HIV-1 infection.
Roger Keith Reeves, Ph.D.
Harvard Medical School, Southborough, MA
Plasmacytoid dendritic cells in immune activation and HIV/SIV persistence: Disease-induced activation and inflammation take a major toll on the body and are associated with premature aging and increased mortality. Evidence indicates chronic inflammation induced by HIV disease has a similar effect on the body, and increased inflammation due to HIV occurs even during treatment-mediated viral suppression. Dr. Reeves will investigate the causes of ongoing activation and inflammation, as well as the long-term consequences. He is particularly interested in characterizing a specific type of immune cell, the plasmacytoid dendritic cell. A better understanding of this mechanism(s) could lead to novel therapeutics to block activation or eliminate latent reservoirs of HIV.
Jonah Sacha, Ph.D.
Oregon Health and Science University, Portland, OR
The role of macrophages as a latent reservoir of HIV: Macrophages are one of the many types of cells composing the immune system and a major target of HIV infection. HIV-infected macrophages live longer and produce more infectious virus than CD4+ T cells, the other major target of HIV. However, the contribution of macrophages to HIV persistence during antiretroviral therapy (ART) remains poorly understood. Novel treatments to eradicate persistent viral reservoirs may need to target macrophages harboring hidden HIV. Dr. Sacha and colleagues propose to directly assess the role of macrophages in viral persistence in a non-human primate model of AIDS. Understanding the contribution of macrophages to viral persistence will guide future approaches to eliminating the residual viral reservoir.
Rafick-Pierre Sékaly, Ph.D.
Vaccine and Gene Therapy Institute Florida, Port St Lucie, FL
Impact of ZFN CCR5-modified autologous CD4 T-cells on HIV persistence: Several gene therapy approaches are being investigated as a means of curing HIV. One clinical trial that has shown promising results used a gene therapy approach to modify the patient’s own cells in the laboratory to make them resistant to virus infection. Dr. Sékaly and colleagues will build on the work already done in this trial to determine if virus becomes undetectable in the blood after stopping antiretroviral therapy. He will monitor immune responses, inflammation, and virus reservoirs in these patients to determine the long-term benefit of this therapy and factors that can improve outcomes of gene therapy and other strategies to cure HIV.