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.   

      2016 HIV Cure Summit   Investigators at amfAR Institute for HIV Cure Research deliver progress report     
  
 
  
    
  
 Normal 
 0 
 
 
 
 
 false 
 false 
 false 
 
 EN-US 
 X-NONE 
 X-NONE 
 
  
  
  
  
  
  
  
  
  
 
 
  
  
  
  
  
  
  
  
  
  
  
  
    
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
   
 
 /* Style Definitions */
 table.MsoNormalTable
	{mso-style-name:"Table Normal";
	mso-tstyle-rowband-size:0;
	mso-tstyle-colband-size:0;
	mso-style-noshow:yes;
	mso-style-priority:99;
	mso-style-parent:"";
	mso-padding-alt:0in 5.4pt 0in 5.4pt;
	mso-para-margin-top:0in;
	mso-para-margin-right:0in;
	mso-para-margin-bottom:8.0pt;
	mso-para-margin-left:0in;
	line-height:107%;
	mso-pagination:widow-orphan;
	font-size:11.0pt;
	font-family:"Calibri",sans-serif;
	mso-ascii-font-family:Calibri;
	mso-ascii-theme-font:minor-latin;
	mso-hansi-font-family:Calibri;
	mso-hansi-theme-font:minor-latin;}
 
      

  

  	
       
      
         
          
             
                  
             
          

          
           
              Dr. Paul Volberding, director of the amfAR Institute for HIV Cure Research  
           
          

         
      
       
    

  


     Exactly 12 months since amfAR established its Institute for HIV Cure Research, Institute researchers reported on their progress at the 2016 World AIDS Day HIV Cure Summit, December 1. The Summit was held at the University of California, San Francisco, where the Institute is based.  “I’d like to thank our entire San Francisco community and especially the people living with HIV that are here with us today,” said Institute Director Dr. Paul Volberding, a professor of medicine at UCSF, in his opening remarks. “Because we want to move as quickly as possible towards a cure, our involvement with the community is especially important.”   Dr. Volberding  is a pioneering HIV/AIDS physician and researcher who encountered his first AIDS patient on his first day of work at San Francisco General Hospital (SFGH) in July 1981. He was a founder of one of the nation’s first AIDS-designated clinics in Ward 86 at SFGH and helped develop the San Francisco Model, a comprehensive HIV treatment model that was emulated around the world.     A Cornerstone of HIV Cure Research   “The Institute forms the cornerstone of our cure research efforts,” said amfAR CEO Kevin Robert Frost. “We’ve made a commitment to invest $100 million in cure research over the next five years and in the first year alone we’ve already committed $40 million to this effort. The Institute represents about $20 million of that.”   Frost said there was broad consensus in the scientific community that the barrier to achieving a cure is overcoming the persistent HIV reservoir.  He introduced a series of  five short animated films  that amfAR has created in an effort to explain the significance of the reservoirs and the challenges involved in locating and depleting them.        </iframe>" data-provider-name="YouTube"         The summit was organized around the four research modules that form the structure of the amfAR Institute and that each relate to the HIV reservoir: Chart, Understand, Record, and Eradicate.   Dr. Peter Hunt  reported on the efforts of his team to chart, or pinpoint, the precise locations of the reservoir. Dr. Hunt’s team is the first to have generated data showing the different cell types that are expressing virus in tissues. In an effort to identify signatures of latently infected cells in tissues, the researchers are using a kind of “facial recognition software for the HIV reservoir.” This sophisticated technology– CyTOF – uses 38 markers to form a multidimensional description of the cells’ surface.     “Shock and Kill”    Dr. Warner Greene  leads the “Understand” module, which is focused on a cure strategy called “shock and kill.” His team is working to identify agents that can effectively “shock” the virus out of hiding so that it can be killed by the immune system or interventions such as a therapeutic vaccine or broadly neutralizing antibodies.  Dr. Greene’s primary focus is on stimulators of the body’s innate immune response called toll-like receptors. “These are the first line of defense – the first barrier,” he said. “What we’re trying to do is to stimulate that response because it magically influences the adaptive immune response – the antibody production and CTL formation. Stimulating these receptors is like the adjuvant that makes vaccines more potent. Maybe if we combine a toll-like receptor agonist with a vaccine, we can make the vaccine more potent, and ideally the toll-like receptor will also act as a shocking agent and make the cells visible for a more efficient attack by the vaccine.”   Dr. Satish Pillai  and his team are charged with recording, or measuring, the size of the persistent HIV reservoir. Dr. Pillai and his colleagues are developing highly sensitive tools that are more effective at identifying tiny amounts of residual virus—as few as ten in a million cells may be infected in a person on antiretroviral therapy. “We’ve teamed up with a company called Raindance Technologies to develop a strategy to identify HIV nucleic acids in clinical samples with unprecedented sensitivity,” Dr, Pillai said.     

  

  	
       
      
         
          
             
                  
             
          

          
           
              amfAR CEO Kevin Robert Frost (right) moderates the panel discussion.  
           
          

         
      
       
    

  


      Testing Cure Interventions    Dr. Steven Deeks , who leads the “Eradicate” module, aims to take the experimental interventions developed by Institute researchers and test them in clinical trials.  “My job for the past year has been to help develop an infrastructure and get all the protocols in place to begin to do studies in people. We’ve done that. And now we’re set to start doing clinical studies of some of the ideas that are coming out of the institute.”  Approximately 200 people attended the half-day summit, which concluded with a lively panel discussion involving all of the presenters along with veteran HIV treatment advocate Matt Sharp.  The 2016 HIV Cure Summit can also be viewed on  amfAR’s Facebook page  or on  YouTube .   The researchers’ presentations are available here:    Introduction/Overview – Dr. Paul Volberding   Professor of Medicine, UCSF Director, UCSF AIDS Research Institute Co-Director, UCSF-Gladstone Center for AIDS Research     Chart – Dr. Peter Hunt   Associate Professor, Division of Experimental Medicine UCSF     Understand – Dr. Warner Greene   Director and Nick and Sue Hellmann Distinguished Professor of Translational Medicine Gladstone Institute of Virology and Immunology Professor of Medicine, Microbiology and Immunology, UCSF Co-Director, UCSF-Gladstone Center for AIDS Research     Record – Dr. Satish Pillai   Associate Professor of Laboratory Medicine, UCSF Associate Investigator, Blood Systems Research Institute     Eradicate – Dr. Steven Deeks   Professor of Medicine UCSF      
  
 Normal 
 0 
 
 
 
 
 false 
 false 
 false 
 
 EN-US 
 X-NONE 
 X-NONE 
 
  
  
  
  
  
  
  
  
  
 
 MicrosoftInternetExplorer4 
 
  
  
  
  
  
  
  
  
  
  
  
  
    
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
   
 
 /* Style Definitions */
 table.MsoNormalTable
	{mso-style-name:"Table Normal";
	mso-tstyle-rowband-size:0;
	mso-tstyle-colband-size:0;
	mso-style-noshow:yes;
	mso-style-priority:99;
	mso-style-parent:"";
	mso-padding-alt:0in 5.4pt 0in 5.4pt;
	mso-para-margin:0in;
	mso-para-margin-bottom:.0001pt;
	mso-pagination:widow-orphan;
	font-size:10.0pt;
	font-family:"Times New Roman",serif;}
 
    

Investigators at amfAR Institute for HIV Cure Research deliver progress report

New amfAR Grants Support Next Generation of Scientists Pursuing Innovative Solutions to HIV/AIDS

New amfAR Grants Support Next Generation of Scientists Pursuing Innovative Solutions to HIV/AIDS

NEW YORK, Oct. 19, 2016 --- amfAR, The Foundation for AIDS Research, on Wednesday announced the 2016 recipients of the Mathilde Krim Fellowships in Basic Biomedical Research, an annual research initiative created to support bright young scientists seeking innovative solutions to HIV/AIDS.

More Than One Way to Activate a Virus

More Than One Way to Activate a Virus

The “shock and kill” approach to eradicating HIV from dormant cell reservoirs is a very active area of HIV research. In these monthly updates, we’ve discussed several drugs, developed to treat a variety of diseases, including cancer and epilepsy, that have the capacity to reverse such a latent state in the test tube.

Wanted: Bioengineers to Cure HIV

Wanted: Bioengineers to Cure HIV

In a revolutionary approach to curing HIV, amfAR is soliciting “novel, high-risk, and potentially high-impact” proposals from bioengineers to address the main barrier to a cure: persistent reservoirs of virus not cleared by antiretroviral therapy (ART).

Shocking HIV Out of Hiding: How Are We Doing?

The key obstacle to an HIV cure remains the reservoir of persistent virus, which is impervious to standard anti-HIV drugs. It has been a target of numerous research teams, many of which are focused on a “shock and kill” approach: dormant HIV-infected cells are activated and thus rendered susceptible to drug- and immune-based attack.

Dr. Sharon Lewin

Dr. Sharon Lewin

However, although a few trials of latency-reversing agents (LRAs) in HIV-positive patients on antiretroviral therapy (ART) have shown the expected increase in cell-associated HIV genetic material in T cells, the frequency of those patients’ latently infected cells hasn’t budged. Writing in the July issue of Current Opinion in HIV and AIDS, amfAR-funded scientist Dr. Sharon Lewin of the University of Melbourne, along with Dr. Thomas Rasmussen from Aarhus University Hospital in Denmark, suggests three reasons for this persistent failure in the clinic.

First, such a strategy demands a robust shock to the latent state. More effective LRAs, possibly used in cocktails similar to combination ART, are required. Second, immune responses that are potent enough to kill those induced virus-expressing cells are needed. Finally, Drs. Lewin and Rasmussen believe more attention should be paid to the role of immune escape mutations among newly awakened virus, i.e., viruses that may evade attempts to destroy them using vaccine strategies or antibodies.

Dr. Warner Greene

Dr. Warner Greene

amfAR is funding several groups to examine those issues, in the test tube and in clinical trials. A recent proof of concept for this approach was provided by amfAR-funded scientist Dr. Warner Greene and colleagues at the University of California, San Francisco. Writing in the prestigious journal Nature Medicine, they recognized that certain types of retinoic acid—vitamin A-based derivatives—can activate genes that increase HIV growth as well as preferentially induce the death of HIV-infected cells.

One of these derivatives is acitretin, an FDA-approved pill for the treatment of psoriasis. Dr. Greene and associates discovered that acitretin was particularly effective in decreasing proviral DNA—a sensitive marker for latency—in CD4+ T cells of HIV-positive individuals on ART, particularly when used together with a common LRA known as SAHA.

At the moment these are promising test-tube experiments. But the authors conclude that their model might be the improved “shock and kill” strategy needed to eliminate all HIV-infected cells.

 

Dr. Laurence is amfAR’s senior scientific consultant.

Can Cancer Treatments Pave the Way to a Cure for HIV?

Can Cancer Treatments Pave the Way to a Cure for HIV?

An amfAR grantee, Dr. Lewin co-chaired the fifth annual Towards an HIV Cure Symposium preceding the 2016 International AIDS Conference in Durban, South Africa, in July. She recently visited amfAR’s offices in New York, where she spoke with amfAR Vice President and Director of Research Dr. Rowena Johnston.

Antibodies as an Important Part of an HIV Cure Strategy

Last month, we reviewed the work of amfAR-funded scientist Dr. Nancy Haigwood of Oregon Health and Science University, who is exploring how to block mother-to-child transmission of HIV. She used a monkey model and a “passive immunotherapy” strategy based on a cocktail of two potent antibodies capable of neutralizing a broad spectrum of AIDS viruses. In the April issue of Nature Medicine, she and her colleagues wrote, “early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs.” And anything that can affect HIV reservoirs is of strong interest to cure researchers.

This point is now being aggressively pursued by amfAR Krim Fellow Dr. Stylianos Bournazos and associates working in the laboratory of Dr. Jeffrey Ravetch at The Rockefeller University in New York. Writing in a May issue of the prestigious journal Science, the researchers reported utilizing a single broadly neutralizing anti-HIV antibody to target infected CD4+ T cells in mice with a humanized immune system (i.e., mice that have been injected with human stem cells). They found that the survival of infected cells could be greatly decreased by this antibody through a process involving an immune receptor known as Fc gamma.

This work is important as antibodies differ from anti-HIV drugs in that they can alter the survival times of both cell-free virus and infected cells. They can also recruit host immune cells to defend against the virus. A variety of different strains of HIV obtained directly from patients were used in this mouse model, and the antibody was equally effective against all of them. In addition, another mouse model mimicking chronic HIV infection demonstrated that such antibodies can accelerate clearance of cells after a longer-term HIV infection.

The authors concluded with this promising statement: “The finding that antibodies can clear infected cells in vivo has important implications for therapies aimed at HIV prevention and viral reservoir reduction or elimination.”


Dr. Laurence is amfAR’s senior scientific consultant.

Using Antibodies to Block Mother-to-Infant Transmission of HIV … and Develop a Cure?

Using Antibodies to Block Mother-to-Infant Transmission of HIV … and Develop a Cure?

Dr. Nancy HaigwoodMother-to-child transmission of HIV remains a significant problem in the resource-poor world. Given appropriate prenatal care, and continuation of antiretroviral therapy (ART) for mother and infant during breastfeeding, over 99% of HIV-positive women can expect to deliver a baby free of HIV.