POZ, December 2012, The POZ 100

While there is still much work to be done in our pursuit of a cure, we are making progress and are excited about the re-energized focus on HIV cure efforts.  We thank POZ and the NIAID/NIH, through their Martin Delaney Collaboratory funding, for continuing to support our vital research.

From POZ

“From scientists and researchers making groundbreaking discoveries to the advocates and politicians on the front lines of the epidemic, this year’s list recognizes people who have made a significant contribution to speeding up the end of AIDS.  Through their efforts, the cure might be closer than you think.”

Keith Jerome, MD, PhD and Hans-Peter Kiem, MD

“Both of the Fred Hutchinson Cancer Research Center in Seattle, Jerome and Kiem are developing proteins known as endonucleases to target HIV.  They’re also collaborating with Sangamo BioSciences to further study the use of gene therapies to render the immune system resistant to the virus.”

Tae-Wook Chun, PhD

“A scientist at the National Institute of Allergy and Infectious Diseases, Chun and his colleagues were among the first to find HIV reservoirs, those long-lived, HIV-infected CD4 cells impervious to ARVs. That was in 1997; since then, he’s been heavily involved in researching was to eradicate them.”

Jim Mullins, PhD

“The professor of microbiology, medicine and laboratory medicine at the University of Washington is working to find an HIV vaccine.  He leads one of the two labs that did genetic analysis of the virus in the RV144 vaccine trial in Thailand, which showed some protection against HIV.”

Ann Woolfrey, MD

“A pediatric oncologist at Seattle Children’s Hospital, she specializes in bone-marrow transplants. She’s the lead investigator for many clinical trials of the Seattle Cancer Care Alliance, including a trial of a mechanism similar to one that cured Timothy Brown of HIV.”

This meeting will bring together researchers associated with each of the three NIH-funded Martin Delaney Collaboratories, other researchers engaged in HIV cure research, investigators in complementary disciplines, and community members to share scientific results and engage in active discussion about the merits of various HIV cure approaches under investigation. (Registration is closed).

For more information, visit the Strategies for an HIV Cure meeting page.

The Call for Letters of Intent is now available on the CIPHER website. Early-stage investigators, who have completed their terminal research degree within the past 10 years and who serve for the first time as primary PI for a non-training research grant, are eligible to apply. Proposals for research projects with the potential to contribute to the optimization of HIV diagnosis, prevention, treatment and care for infants, children and adolescents affected by HIV in resource-limited settings by responding to identified research gaps (see list of eligible research topics) can be submitted by 26 November 2012.

Up to 10 research projects worth up to $75,000 per year for a maximum of two years will be awarded at the 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) in Kuala Lumpur, Malaysia, from 30 June to 3 July 2013.

CIPHER Research Grant Team

Research Promotion
International AIDS Society
Avenue de France 23 | CH-1202 Geneva | Switzerland
Tel: +41 22 7100 843 | Fax: +41 22 7100 899
Email: cipher@iasociety.org
Web: www.iasociety.org

We’re pleased to announce the publication of our inaugural defeatHIV Newsletter!

As we strive towards a cure, we hope this newsletter will keep both the public and scientific communities informed of our collaboratory operations and research efforts. Inside our first issue you will find an introduction to our collaboratory, an overview of our clinical studies and a look ahead to the November NIH-sponsored joint Martin Delaney Collaboratory meeting.

Visit our newsletter page to download, subscribe, and learn more about this exciting new publication!

Dr. Richard Harrigan

Richard Harrigan, Director, Center for Excellence in HIV/AIDS, University of British Columbia

Dr. Richard Harrigan is the Director of Research Laboratories at the BC Centre for Excellence in HIV/AIDS. His work primarily focuses on HIV drug efficacy, drug resistance, and the human and viral parameters that influence HIV disease progression. At the BC Centre for Excellence in HIV/AIDS, his work has involved investigations using three major cohort studies, as well as the more than five thousand patients in the BC Drug Treatment Program.

Before working at the CfE, Dr. Harrigan was at the pharmaceutical companies Wellcome and Glaxo Wellcome in the United Kingdom. Dr. Harrigan was also one of the first to demonstrate the potential clinical utility of HIV drug resistance testing and introduced one of the world’s first broadly based clinical HIV drug resistance testing programs; this program has tested more than 50,000 clinical samples from across Canada. Dr Harrigan is currently investigating the application of newer “deep-sequencing” technologies in the clinical management of HIV therapies.

Dr. Harrigan holds the Glen-Hillson Professorship in Clinical HIV Virology and the CIHR-GSK Research Chair in HIV/AIDS at the University of British Columbia, and is an Associate Professor in the Division of AIDS (Faculty of Medicine) at the University of British Columbia.

Photo courtesy of Dean Forbes, © 2006

Currently, defeatHIV clinical studies are focused on treating HIV infected individuals who also suffer from hematologic malignancies such as leukemia or lymphoma. While today’s HIV therapy can often suppress the virus and minimize its effects on the body, the combination of HIV and cancer diagnoses has historically been difficult for clinicians to manage. The powerful drugs often required to treat blood cancers can exacerbate the HIV infection, ultimately making things worse for the patient. However, recent advances in hematopoietic cell transplantation (HCT) have demonstrated remarkable results in people suffering from HIV and cancers of the blood (see Berlin Patient). Our goal is to build on these successes and utilize our expertise in HIV virology, transplantation biology and genome editing technologies to develop a new therapeutic approach for eradicating HIV.

We hope this information will serve as a resource for patients, clinicians and other individuals interested in our clinical research efforts. Follow the link to our Clinical Studies page and learn more about these studies, eligibility criteria and clinic contact information.

Seattle Cancer Care Alliance (SCCA)

First defeatHIV Clinical Study Is Enrolling!
We are excited to announce recruitment for the first defeatHIV clinical study is open! This is an important step in our HIV eradication efforts and as such, we will be updating defeatHIV.org to include further information on our clinical studies for HIV patients. Read on for study details, eligibility criteria and clinic contact information.

Protocol 1410: Treatment with Allogeneic Hematopoietic Stem Cell Transplantation for Induction of Mixed Hematopoietic Chimerism in Patients Infected with Human Immunodeficiency Virus-1 Using a Non-Ablative Conditioning Regimen Containing Total Body Irradiation in Combination with Post-Transplant Immunosuppression with Cyclosporine and Mycophenolate Mofetil

Purpose: The purpose of the treatment on this study is to replace bone marrow cells with healthy cells donated by a person with a healthy immune system. The new bone marrow or hematopoietic stem cells have the ability to grow into new blood and immune systems. We believe that HAART may give us a new way to help control the HIV and prevent it from infecting the new bone marrow cells. We will monitor the level of HIV in the latent reservoir to determine whether HAART drugs can continue to control or even reduce HIV after hematopoietic stem cell transplantation (HSCT).

Major eligibility criteria:

1. Patients with a hematologic malignancy in remission treatable with HSCT, who:
   a. have been on HAART for at least one month, and
   b. have a HIV load <5000 copies/ml.
2. Or, Patients without malignancy who meet these criteria:
   a. have been treated with more than one HAART regimen for at least six continuous months, and
   b. have a HIV load <50 copies/ml, and
   c. have a CD4 count <100 cells/ml.
3. Patients must have an HLA-matched donor.
4. Patients must be <65 years old.

Contact: For more information, contact the Clinical Coordinator Office at the Seattle Cancer Care Alliance (1-800-804-8824) and reference protocol number 1410.

defeatHIV clinical studies are performed in Seattle, WA at the Seattle Cancer Care Alliance (SCCA). The SCCA is the treatment arm of the world-renowned Fred Hutchinson Cancer Research Center, and operates the largest bone marrow transplant program in the world.

On May 31, 2012 the defeatHIV Martin Delaney Collaboratory held its first Annual Meeting at the Fred Hutchinson Cancer Research Center in Seattle, WA. defeatHIV investigators from the Hutchinson Center, University of Washington, Seattle Children’s Hospital, City of Hope, Sangamo BioSciences and NIH participated in what was a productive review of the collaboratory’s operational and scientific accomplishments in our first year of funding.

Also taking part were members of the defeatHIV Scientific Advisory Panel, whose comments and feedback on Year 1 progress will provide further refinement of our approaches and facilitate achievement of our milestones.

Look for more details on our progress in Year 1, and goals for Year 2, in the defeatHIV Newsletter arriving soon! Subscribe here.

MRI of the brain (subject two). Axial T1 post gadolinium images.
A. Enhancing lesion in the right parietal lobe (arrow) at the time of initial presentation.
B. First post-radiation scan, enlargement of the enhancing area and associated vasogenic edema (arrow heads) are present (radiographically imaging findings were thought to represent possible pseudoprogression).
C. Six months from the original diagnosis, after 2 cycles of temozolomide and O-6-BG, area of enhancement has enlarged but surrounding edema has diminished and patient was clinically stable.
D. Eleven months from the original diagnosis, after two additional doses of temozolomide with O-6-BG. Area of contrast enhancement is stable.

In this study, defeatHIV co-PI Hans-Peter Kiem of the Fred Hutchinson Cancer Research Center has led a team of researchers in demonstrating the therapeutic potential of gene-modified, chemotherapy-resistant hematopoietic stem cells (HSCs).

Read | Science Translational Medicine commentary: A Shield Against Chemotherapy

What, might you ask, does cancer or chemo-resistant stem cells have to do with our HIV eradication efforts?

Dr. Kiem, along with fellow defeatHIV investigators Drs. Philip Gregory and Michael Holmes, are currently leading a key defeatHIV initiative to develop and test HIV-resistant stem cells in a preclinical model (see descriptions of Projects 2 & 3). Transplant optimization in a preclinical model is essential before clinical testing in people can begin. To this end, generating high levels of the HIV-resistant stem cells following transplant will be an important component of the model optimization. If the HIV-resistant stem cells were also chemo-resistant, this would provide a distinct advantage to their expansion over healthy unmodified cells following chemotherapy.

If we can demonstrate this method of selection for HIV-resistant cells is safe and effective in the preclinical model, we will apply the technique in clinical studies involving HIV-infected individuals requiring bone marrow transplant for hematologic malignancies.

More details on our clinical studies involving HIV-infected subjects are forthcoming. Stay tuned for updates on defeatHIV.org and in our upcoming Newsletter! Subscribe here.

Read | Extended Survival of Glioblastoma Patients After Chemoprotective HSC Gene Therapy
(Journal subscription required)

Investigators from defeatHIV and the Delaney AIDS Research Enterprise (DARE), two of the three NIAID Martin Delaney Collaboratories, partner to review HSC-based gene therapy strategies for HIV disease – demonstrating how scientists in the field are uniting in the fight against HIV.

Read | Hematopoietic-Stem-Cell-Based Gene Therapy for HIV Disease
(Journal subscription required)