|Front Row (L to R): Mike Busch, MD, PhD [REDS-III Central Lab PI], Mila Lebedeva [Research Associate], Sheila Keating, PhD [Lead-Core Immunology]. Back Row (L to R): Graham Simmons, PhD [Investigator-Viral Entry], Philip Norris, MD [REDS-III CL Co-Investigator], Eric Delwart, PhD, [Investigator-Virology], Mars Stone, PhD [Lead-Viral Reference and Repository Core].|
This is the last installment in a three-part series about the NHLBI AIDS Program. The first installment covered the program’s work within the cardiovascular space. The second installment discussed the intersection between HIV research and lung research.
Tremendous progress in the treatment of HIV has led to increased survival and a dramatic evolution of the disease’s course in patients. The clinical challenges confronting the population have now shifted from AIDS-related illnesses to chronic diseases, such as coronary artery disease, chronic obstructive lung disease, and chronic anemia. Multiple studies have demonstrated that the risk of developing heart, lung, and blood (HLB) disease in HIV patients is significantly higher and may be accelerated compared to the general population. In addition, the mechanisms of HIV-related HLB disease may be different because of the adverse effects of antiretroviral therapy (ART) and a greater contribution of inflammation and other factors.
According to Monica Shah, M.D., NHLBI AIDS Coordinator, the increasing burden of heart, lung, and blood diseases on this population is an important issue from both a public health and scientific standpoint, and the NHLBI is uniquely poised to take a leadership role in supporting research that addresses the new phase of the HIV epidemic. The NHLBI AIDS Program supports a robust portfolio of HIV-related grants and has recently issued a number of funding opportunities, which can be found on its website.
In February 2009, a medical team in Germany published a paper in the New England Journal of Medicine with findings that rocked both the scientific community and the lay public. A team of doctors had treated a 40-year-old, HIV-positive man for acute myeloid leukemia with an allogeneic stem cell transplantation. The doctors used a transplant from an HLA-matched, unrelated donor who had a CCR5 mutation, which makes cells resistant to HIV entry. An unexpected result of the procedure was that the transplant not only treated the patient’s leukemia but also appeared to eliminate the HIV from his system.
“What this result showed us is that there might be a way, somehow, to ‘cure’ someone of HIV, be it through cell therapies including those based on hematopoietic stem cells, the medications used in supporting the transplantation, or a combination of the two,” said Simone Glynn MD, MSc, MPH, the branch chief for the Transfusion Medicine and Cellular Therapeutics Branch in the NHLBI’s Division of Blood Diseases and Resources.
“This caught everyone’s attention because currently even with aggressive early treatment with antiretroviral medications and the ability to reduce viral load to undetectable levels, HIV does not appear to be completely eliminated from the body,” said Dr. Glynn. “Scientists and researchers started asking these questions. Was it the transplanted, HIV-resistant stem cells themselves? The conditioning regimen? Something having to do with the immunological reactions after transplantation?
“There is now a lot of research being done to look for a cure to HIV that goes beyond using only anti-retroviral therapies,” she said. “Now we’re looking into the possibilities of cell therapies or other unique therapies such as novel gene therapies and the development of non-traditional antiviral strategies that may be the answer.”
And the NHLBI’s Division of Blood Diseases and Disorders (DBDR) is eager to support this line of research in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID). Earlier this year, NIAID and NHLBI issued a Notice of Intent (NOT) to publish a Funding Opportunity Announcement (FOA) for “Beyond HAART: Innovative Approaches to Cure HIV-1.”
“The NHLBI has a strong interest in pursuing novel therapies – such as cell therapy and gene therapy – toward a cure for HIV,” Dr. Glynn said. “The objective of this FOA is to encourage the development of new non drug-based approaches by supporting research that will help us understand, simplify and improve on existing cell- and gene-based strategies to eliminate HIV.”
“Right now, everybody in the HIV field is talking about new approaches and searching for a way to actually cure HIV rather than just treat it or prevent it,” she added.
Dr. Glynn also emphasized that the forthcoming FOA, which should be released in early 2014, is a strong example of cross-institute collaboration within NIH.
Beyond studying potential cures, the NHLBI’s Division of Blood Diseases and Disorders is looking to support research that is in line with the NIH AIDS Strategic Plan, including research that could target the impact of HIV infection on the hematopoietic system as well as on the endothelium, understanding how HIV affects coagulation pathways and biomarkers of thrombosis, and evaluating the interactions of HIV with host elements and the microbiome. Additionally, the NHLBI’s Division of Blood Diseases and Disorders, through its unique responsibility at NIH to support research and research training on the safety of blood and blood components for transfusion, actively supports research to minimize the risks of transmitting HIV and other infections through transfusion through its current support of the Recipient Epidemiology and Donor Evaluation Study (REDS-III) research program.
Of note, the REDS-III program currently is conducting a study to enhance and standardize the methods to stage HIV infection in blood donors and characterize the HIV viral sequences across the US, Brazil, China, and South Africa using state of the art methodology. According to Dr. Glynn, one of the greatest challenges facing development and optimal performance of HIV blood screening, diagnostic and viral load assays, as well as therapeutics and vaccines, is the rapidly evolving genetic diversity of HIV-1. Tracking this circulating genetic diversity through collaborative international “molecular surveillance” programs is critical to understanding viral evolution and assuring optimal performance of blood screening tests, clinical diagnostics and anti-retroviral therapeutics, and to guide development of immunogens for vaccines that are maximally representative of contemporary regional/global transmitted HIV-1 viruses.
Collaboration is Key
While the NHLBI AIDS Program encompasses many diverse scientific areas, an important unifying theme is the emphasis on collaboration, teamwork, and communication.
“A key mission of the NHLBI AIDS Program is to support multi-disciplinary collaboration among diverse research communities,” Dr. Shah said. “We encourage the heart, lung, and blood scientific communities to collaborate with researchers in other fields. We believe that partnership and collaboration are critical to advancing the field of HIV-related heart, lung, and blood disease.”