Pursuit of HIV Cure Gets Funding Boost from amfAR

amfAR Consortium allows five teams of researchers to collaborate on studies aimed at eliminating HIV

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A network of leading HIV/AIDS researchers are continuing to pave the road toward a cure for HIV with a boost of funding on Wednesday from amfAR, the Foundation for AIDS Research. The research grants, totaling more than $913,000, will enable five teams of scientists working at leading research institutions in the United States and around the globe to collaborate on studies aimed at curing HIV.

The latest round of grants is part of amfAR’s Research Consortium on HIV Eradication (ARCHE) program, an initiative launched in 2010 focused on exploring potential strategies for eliminating HIV infection. Projects in this year’s ARCHE program include: ongoing efforts to study HIV-positive patients who received stem cell transplants; explore ways to cure HIV by reactivating latent virus; test a vaccine as a functional cure for simian immunodeficiency virus (SIV) in monkeys; and explore how gender-specific differences can affect how HIV can be cured.

“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.”   

One ARCHE grantee, Dr. Timothy Henrich of Brigham and Women’s Hospital in Massachusetts, recently reported that two patients who had appeared to be free of HIV following stem-cell transplants had each experienced a resurgence of virus. Dr. Henrich, along with Katherine Stephenson, M.D. of Beth Israel Deaconess Medical Center in Boston and Marcello Wolf, M.D. of Clinica Santa Maria in Santiago, Chile plans to continue following up on the two patients, as well as study other HIV-positive patients who received stem cell transplants, which have the potential to teach important lessons about how the Berlin Patient was cured and how this strategy could be broadly applied to others living with HIV.

Building on progress from a previous ARCHE grant, Eric Arts, Ph.D. of Case Western University in Cleveland will work with Ronald Veazey, Ph.D. at the Tulane Primate Center in Covington, Louisiana and a team of researchers in the United Kingdom to test an experimental vaccine in monkeys with SIV. The vaccine would be aimed at cells that harbor latent virus that otherwise cannot be targeted with antiretroviral therapy, and in effect, would help remove the viral reservoirs, representing a key step toward curing HIV.

In another study, researchers led by Cynthia Gay, M.D. of University of North Carolina and Catherine Bollard, M.D. of the Children’s National Medical Center in Washington, D.C. will explore a way to cure HIV by taking a patient’s cytotoxic T cells, an important player in the immune system, and reprogramming them “in vivo” to  specifically kill HIV-infected cells. Once the cells are injected back into the HIV patients, the researchers will examine if the procedure reduces the number of cells that harbor latent HIV.

Finally, two teams of researchers led by Jonathan Karn, Ph.D. of Case Western Reserve University and Eileen Scully, M.D., Ph.D. of Massachusetts General Hospital in Cambridge, Massachusetts will explore how gender-based differences can affect how HIV is cured. Working alongside Nicolas Chomont, Ph.D. of Vaccine and Gene Therapy Institute of Florida and Steven Deeks, M.D. of University of California San Francisco, Dr. Karn will study and compare the key differences of latent virus in men and women, especially when reactivated, a key component to a leading strategy to cure HIV. Dr. Scully will also work with Drs. Chomont and Deeks to explore the immune profile, activation levels and distribution of latent viral reservoirs in men and women.

“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.”

ARCHE-funded research teams and their projects are as follows:

Case Western Reserve University, Cleveland, OH
Eric Arts, Ph.D. – principal investigator
Ronald Veazey, DVM, Ph.D. – collaborating investigator (Tulane Primate Center)
$187,341
ID: 108838

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.

University of North Carolina, Chapel Hill, NC
Cynthia Gay, M.D. - principal investigator
Catherine Bollard, M.D. – collaborating investigator (Children’s National Medical Center, Washington, DC)
$58,338
ID: 108839
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.

Brigham and Women's Hospital, Cambridge, MA
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)
$191,039
ID: 108840

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.

Case Western Reserve University, Cleveland, OH
Jonathan Karn, Ph.D. - principal investigator
Nicolas Chomont, Ph.D. - collaborating investigator (VGTI-FL)
Steven Deeks, M.D. - collaborating investigator (UCSF)
$222,156
ID: 108841

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.

Massachusetts General Hospital, Cambridge, MA
Eileen Scully, M.D., Ph.D. - principal investigator
Nicolas Chomont, Ph.D. - collaborating investigator (VGTI-FL)
Steven Deeks, M.D. - collaborating investigator (UCSF)
$254,930
ID: 108842

Impact of sex-based differences on HIV resevoir 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.