HIV Cure Research Gets Million Dollar Boost From amfAR

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amfAR

The Foundation for AIDS Research (or amfAR) announced Wednesday it’s giving grants to five teams of scientists working at “leading research institutions in the U.S. and around the globe to collaborate on studies aimed at curing HIV.”

The money will be siphoned out through amfAR’s Research Consortium on HIV Eradication (ARCHE) program. Its point is to support “collaborative teams of biomedical researchers exploring strategies for eradicating HIV infection.” While that leaves a large array of research open to the grants, the release from amfAR detailed each recipient receiving a chunk of the $913,000 that’s going out. Since 1985, amfAR has invested more than $366 million in its programs and has awarded grants to more than 2,000 research teams worldwide.

“We have made marked progress in HIV research, and the pursuit of a cure has never been greater at amfAR,” said amfAR CEO Kevin Robert Frost. “The ARCHE program exemplifies this drive, and we must keep the momentum going to accelerate this process by continuing to provide much-needed resources and encourage some of the world’s leading researchers to collaborate around this goal.”

While some advocacy groups are fighting to make things more common across the epidemic (like achieving equality and non-discrimination), amfAR is still looking at the very complex parts of it.

“While we’re steadily closing in on leading strategies that will help us cure HIV, there are still plenty of hurdles to cross, such as figuring out viable ways to purge reservoirs of dormant HIV or gain a better understanding of the CCR5 protein,” said Rowena Johnston, Ph.D., amfAR’s vice president and director of research. “The latest round of ARCHE grants will give us the opportunity to explore these strategies, and piecing together these findings will help enrich our understanding of the disease, which will one day lead to a cure.”

Here are the grant recipients in ascending order of the grants they got, with descriptions from amfAR...

How much: $58,338

Where:

University of North Carolina, Chapel Hill, NC

Who:

Cynthia Gay, M.D. - principal investigator

Catherine Bollard, M.D. – collaborating investigator (Children’s National Medical Center, Washington, DC)

The research:

Safety And Immunologic and Virologic Response to HIV-CTL Therapy in HIV Infection: One of the ways researchers are attempting to cure HIV is by reactivating latent virus, which would then be killed by antiretroviral therapy, and killing the remaining infected cells. The immune system will likely be an important part of killing those infected cells, and yet HIV infection compromises the ability of the immune system to fight infections. Dr. Gay and colleagues want to boost the ability of cytotoxic T cells — a key element of the immune system that kills infected cells — by taking a patient's own cells and "educating" them in a test tube to kill HIV-infected cells. Those cells would then be infused back into the patient. In order to test this concept, Dr. Gay will work with colleagues to produce such boosted cells at a clinical grade, and will then infuse them back into patients to determine the extent to which they reduce the number of cells that harbor latent HIV infection.

How much: $187,341

Where:

Case Western Reserve University, Cleveland, OH

Who:

Eric Arts, Ph.D. – principal investigator

Ronald Veazey, DVM, Ph.D. – collaborating investigator (Tulane Primate Center)

The research:

A functional cure of SIV in macaques: model for ongoing ARCHE human trials: To supplement ongoing work in another ARCHE grant, Dr. Arts will work with Dr. Veazey to test an experimental vaccine in monkeys. Dr. Arts is designing the vaccine with colleagues at Case Western Reserve University and at various institutions in the United Kingdom. The vaccine is derived from a patient's own virus and is intended to target those cells that harbor latent virus that cannot be targeted with antiretroviral therapy. Promising preliminary data using the vaccine in patients' cells indicate that the vaccine may help to purge viral reservoirs and may thus represent a key step towards curing HIV. Drs. Arts and Veazey now plan to leverage resources from institutional partners to test whether the vaccine works in monkeys - if so, this would represent an important milestone towards testing the vaccine in humans.

How much: $191,039

Where:

Brigham and Women's Hospital, Cambridge, MA

Who:

Timothy Henrich, M.D. - principal investigator

Katherine Stephenson, M.D. – collaborating investigator (Beth Israel Deaconess Medical Center, Boston, MA)

Marcello Wolf, M.D. – collaborating investigator (Clinica Santa Maria, Santiago, Chile)

The research:

Allogeneic Stem Cell Transplantation and HIV-1 Persistence: In the summer of 2013, Dr. Henrich announced that virus levels in two patients he had been studying with ARCHE funding had remained undetectable for 8 and 15 weeks after they stopped taking their medications. They had previously received stem cell transplants to treat their cancer, but unlike the Berlin Patient, the stem cell donors in both cases had normal cells rather than mutated cells lacking CCR5. Dr. Henrich plans to use this ARCHE grant to continue following up on these two patients, to determine how long their virus remains undetectable, and to track the consequences should signs of the virus return. He and his colleagues will continue to track the fates of other HIV-positive patients who receive stem cell transplants, such as another HIV-positive patient who received a transplant from a donor who lacked CCR5. These studies have the potential to teach us more about how the Berlin Patient was cured, and how those lessons might be more broadly applied to others.

How much: $222,156

Where:

Case Western Reserve University, Cleveland, OH

Who:

Jonathan Karn, Ph.D. - principal investigator

Nicolas Chomont, Ph.D. - collaborating investigator (VGTI-FL)

Steven Deeks, M.D. - collaborating investigator (UCSF)

The research:

Gender-specific differences affecting reactivation of latent HIV: In concert with another ARCHE project led by Dr. Eileen Scully, Drs. Karn, Chomont and Deeks will investigate the potential for sex differences to affect how HIV can be cured. Specifically, this team will examine the degree to which virus in women versus men is latent, and any differences in the mechanisms whereby that virus is maintained in a latent state. It has recently been demonstrated that the estrogen receptor, which is located on the nucleus, suppresses HIV transcription through a complex signaling pathway. Dr. Karn and colleagues will measure the size of the latent reservoir, its location within specific spans of DNA, and the ease with which it can be reactivated by biological as well as pharmacological tools. Since reactivation of latent virus is a key component to a leading strategy to cure HIV, it will be important to determine whether the sexes differ in their ability to respond to this treatment.

How much: $254,930

Where:

Massachusetts General Hospital, Cambridge, MA

Who:

Eileen Scully, M.D., Ph.D. - principal investigator

Nicolas Chomont, Ph.D. - collaborating investigator (VGTI-FL)

Steven Deeks, M.D. - collaborating investigator (UCSF)

The research:

Impact of sex-based differences on HIV reservoir size and immune activation: In concert with another ARCHE project led by Dr. Jonathan Karn, Drs. Scully, Chomont and Deeks will investigate the potential for sex differences to affect how HIV can be cured. Specifically, this team will examine the immune profile, including levels of activation, as well as the distribution of the latent reservoir, in men versus women. These studies are driven by well known but little understood sex differences in HIV pathogenesis, including lower viral loads, higher CD4 counts and faster disease progression in women. It is also well known that the immune system of women is on average more activated and activatable than that of men. Despite this, no studies to date have addressed whether there are sex differences in the reservoir that might reasonably result from the sex differences in pathogenesis. Because very few women are included in clinical studies of curative interventions, these studies led by Dr. Scully will shed much-needed light on the need to study women more closely in the search for a cure.

For more information, go to amfar.org.


Greg Kabel

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