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Stefanie transferring the white blood cells
Stefanie transferring the white blood cells

In my last post, you learned about AIDS Research Alliance’s first leukapheresis procedure, and why our research team needs to collect white blood cells in order to advance ARA’s HIV cure research.

Since I wrote my last post, we have performed leukapheresis on several more study volunteers, and I have worked to perfect our process for isolating the resting CD4 T cells, which contain the HIV reservoir, from the white blood cells that we collect from each volunteer.

The HIV reservoir is the barrier to curing HIV. The viral reservoir is “invisible” to the immune system and antiretroviral therapy, so they can’t attack it. But when ART is discontinued, the reservoir can be activated, and the virus will come roaring back if ART is not resumed.

So as researchers working to find a cure for HIV, we at ARA need to focus on the reservoir. But isolating the HIV reservoir is not easy work. Why? Because the reservoir cells are extremely rare. To give you an idea,

  1. First, we must conduct leukapheresis on a study volunteer to extract the white blood cells from their blood.
  2. Then, from the white blood cells, we select the resting CD4 T cells, which are only 3-11% of all the white blood cells.
  3. Of these resting CD4 T cells, only one in one million is an HIV reservoir cell.

To make it all the more complicated, we cannot “see” the reservoir cells; we have to detect them by other means.

So, before we can begin our prostratin research, we must confirm that our research process for isolating the reservoir cells will work.

So far, our process looks to be accurate and effective. I have already extracted the resting CD4 T cells from the leukopak solution. I tested this population of cells, and found it to be 97% pure resting CD4 T cells. Pretty high!

Our next step is to work with the UCLA Virology Core Lab, using their assay in combination with a new assay developed at Robert F. Siliciano’s Lab at Johns Hopkins, to quantify how much virus our reservoir cells produce when stimulated. This way, we can determine which concentrations of prostratin are able to stimulate the reservoir cells in our sample. We will use this information when we conduct our prostratin research to understand how potent prostratin is, and to answer the question—which doses of prostratin induce the reservoir cells to produce virus without being harmful to the human body?

Confirming that our systems are working properly and are sensitive enough to detect the small amounts of virus produced by the rare reservoir cells is no easy thing. But with the help of our collaborators, our research volunteers, and you, our community, we are moving closer to our goal – HIV cure research that could change the course of 35 million lives, and more.

If you have any questions about our work, please contact our team anytime at communications@aidsresearch.org

Thank you for your continued support,

Stefanie

Stefanie showing us how the cells are separated
Stefanie showing us how the cells are separated

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Our technician overseeing the leukapheresis
Our technician overseeing the leukapheresis

Just last week, we at AIDS Research Alliance reached an important milestone: We conducted our first leukapheresis procedure, working with an HIV-positive patient to extract white blood cells, which harbor the rare HIV reservoir cells, from his blood. Why is this important? Because the reservoir cells are what prevent doctors from curing HIV/AIDS. By having a sample of these cells, we will be able to advance our studies, testing prostratin’s activation efficacy on the reservoirs.

On a Tuesday morning, Eric, our study volunteer, came into our clinic to have his white blood cells extracted by our apheresis machine. After four hours, we had generated what we needed to perform the next step in our prostratin studies: a “leukopak,” or a solution of white blood cells. These white blood cells contain the HIV reservoir cells. Only about five percent of these white blood cells are memory CD4 T cells, and of those, only one in a million harbors latent HIV.

This is an important step in our cure research, which will help the scientific community better understand how we can eliminate the reservoir, and cure HIV/AIDS. Eric explained to me why he was participating in this research, “I watch The Walking Dead. When I watch it, I think about what would happen to me if society fell apart, if hospitals shut down and we didn’t have access to HIV medications. I would be dead. Finding a cure means survival.”

AIDS Research Alliance’s ability to generate a leukopak of white blood cells from an HIV positive volunteer is unique. Not many research labs have the ability and machine to procure white blood cells from HIV positive volunteers, and very few research labs have the capability to generate this cell sample in-house. Having the volunteer well characterized, and having extracted the cells at AIDS Research Alliance, we have valuable insight into the time of the cell donor’s initial infection, possible co-infections, and his drug adherence history. This will help us better understand how these variables influence our experiments and their outcomes.

Next, I will move from the clinic into the research lab, where I will extract the HIV reservoir cells from the patient’s white blood cells. Stay tuned for my next update, where I will show you how I do that, and what I find.

Stefanie

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Martha Williamson performing at WAD2013
Martha Williamson performing at WAD2013

Due to your generosity, AIDS Research Alliance is able to continue its work on its most important research initiative - the search for a cure for HIV/AIDS.

The recent expansion of our laboratory has given me more space to conduct the FDA  required experiments on our drug candidate, prostratin, and to conduct additional studies with Dr. Otto Yang of UCLA. Early experiments on prostratin's effect on the HIV reservoirs look promising. 

Outside of the laboratory, I had the pleasure to attend ARA's World AIDS Day Concert at The Colburn School for the first time. The presentations underscored the urgency of  continued HIV/AIDS research. This year, we honored Robin Smalley,  International Director and Co-Founder of Mothers2Mothers, an  organization that works to prevent the transmission of HIV from mother  to child in Africa. The research that lead to better treatments for HIV made the progress of Mothers2Mothers possible. AIDS Research Alliance was involved in the development of half of those drugs.

Just imagine if we could find a cure for HIV within the  next decade. What would this mean to the more than 35 million people  living with HIV worldwide, to the almost 3 million more who will  unfortunately become infected with HIV within next year, or to the  thousands of children who are infected with HIV every week?

Every year, World AIDS Day reminds us that AIDS is not over. See the attached article published in the Los Angeles Times, by Dr. Warner Greene of the Blackstone Institute of the University of California, San Francisco,  which validates the continuing urgency for HIV/AIDS research. 

I would like to take this opportunity to thank you again for your past support, and to wish you a happy holiday season.

Warm regards,

Stefanie

W. David Hardy, M.D. with Stefanie Homann, Ph.D.
W. David Hardy, M.D. with Stefanie Homann, Ph.D.

Links:

Stefanie Homann
Stefanie Homann

Dear Friend,

I would like to thank all of you for your interest in ARA. Your support helped us to expand our research lab and allows me to continue our research on the HIV reservoirs by using the leukapheresis samples and prostratin.

Over the last 3 months we gathered the required reagents to study prostratin’s effect on the HIV reservoirs, and expanded our scientific approach by including other cell types that play a large role in HIV latency. To be able to study other types of reservoir cells, we received a model virus from a new collaborator at John Hopkins University and will start the research experiments next week.

Furthermore, we have the incubators running, and started the cell lines for the FDA-required experiments. This is exciting progress, and I am very much looking forward to sharing our results and future progress with you.

Thank you very much!

Stefanie 

 

 

Dr. Homann earned her PhD in Virology from the University Hospital of Heidelberg, Department of Infectious Diseases, in Germany.  She is published in several peer-reviewed journals, including "Virus replication and CD4+ cell depletion by HIV-1 Nef in ex vivo human tonsil histocultures." Dr. Homann was a Postdoctoral Fellow at the University of California, San Diego, Department of Medicine, Infectious Diseases, under Dr. John Guatelli. While at UCSD, Dr. Homann developed a number of research projects, including "The antiviral restriction factor BST-2 in HIV infection in vivo and in vitro," and "The accessory HIV Nef protein and infectivity enhancement."

Stefanie Homann, Ph.D.
Stefanie Homann, Ph.D.

Dear Friends,

A new scientist has joined ARA. Our staff is energized by Dr. Stefanie Homann's vast knowledge of HIV/AIDS and impressed with her academic and career accomplishments. Dr. Homann earned her PhD in Virology from the University Hospital of Heidelberg, Department of Infectious Diseases, in Germany. 

She is published in several peer-reviewed journals, including "Virus replication and CD4+ cell depletion by HIV-1 Nef in ex vivo human tonsil histocultures." Dr. Homann was a Postdoctoral Fellow at the University of California, San Diego, Department of Medicine, Infectious Diseases, under Dr. John Guatelli. While at UCSD, Dr. Homann developed a number of research projects, including "The antiviral restriction factor BST-2 in HIV infection in vivo and in vitro," and "The accessory HIV Nef protein and infectivity enhancement."

We believe Dr. Homann brings technical expertise and scientific knowledge that will contribute to the success of ARA's research program, particularly our work targeting the HIV reservoirs [prostratin]. Thank you again for supporting our work. 

Sincerely,

Steve

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Organization

AIDS Research Alliance

Los Angeles, CA, United States

Project Leader

Emma Brownell

Los Angeles, CA, United States

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