Goal of Newly Awarded Grant: Increase HIV Research by 25 Percent

Partnership with African Experts To Bring Researchers Closer to the Epidemic

June 04, 2008

The University of Rochester today announced that the National Institutes of Health (NIH) has awarded a team of more than 50 researchers a five-year, $3.2 million grant. The award is designed to join HIV/AIDS researchers from across university with experts from outside of both the field, and the United States, in unprecedented collaborations. In that spirit, one wing of grant projects will be conducted in partnership with seasoned South African researchers working at the heart of the epidemic, where one in five people is infected.

The grant will establish at the University of Rochester a Developmental Center for AIDS Research (D-CFAR), a “mini-network” of services, technical capabilities and funding mechanisms designed to increase the overall quality and quantity of HIV/AIDS research at the university and its partners. Specifically, the five-year goals of the project are to bring about 25 percent increases in the university’s federal HIV research funding and research faculty size. To achieve these goals, the project will fund pilot studies that enable recently recruited researchers to gather enough preliminary data to be obtain their own grants within five years.

Recent initiatives make the timing of the D-CFAR’s inception opportune. First, the university was one of the first to win a Clinical and Translational Science Award (CTSA) from the NIH in 2006, the success of which is closely linked to the D-CFAR proposal. The funding and mentoring programs, the pilot and collaborative studies within the D-CFAR are modeled on CTSA mechanisms, and like the CTSA, the D-CFAR aims to translate science into new treatments. Secondly, the University of Rochester Medical Center recently launched its 2007-2012 Strategic Plan, which devotes resources to nine high-priority programs. Two of the nine, infectious disease and nanomedicine, are also research priorities for the center.

“In the process of writing this grant, we realized just how many people at the university are working on HIV research here that we never would have come across,” said Michael Keefer, M.D., professor of Medicine at the Medical Center and co-director of the D-CFAR. “Where many grants I have been involved with focus on a very specific area of research done at many universities, the CFAR model establishes large-scale collaboration at one institution, an all-encompassing approach. Accordingly, the grant will support research projects led out of the University of Rochester River Campus and the School of Nursing, as well as the Medical Center.“

Core Competency

Founded in 1998, the Centers for AIDS Research (CFAR) program is funded by seven of the National Institutes of Health and provides administrative and research support for AIDS research projects. There were 19 mature CFARs as of 2007, including those at the New York University School of Medicine, the University of Pennsylvania and Harvard. The University of Rochester has won a “developmental” CFAR award for first-time applicants, which includes about half the budget of a mature CFAR. It sets the stage for the team to apply for a full CFAR in five years.

To be included in this exclusive program, the University of Rochester had to demonstrate formidable strength in the many areas of HIV/AIDS research and patient care. Strength areas identified in the D-CFAR proposal were translational immunology and vaccine development, antiretrovirals and virology, neuroAIDS and opportunistic infections.

Ongoing efforts with translational immunology, for instance, look at how the immune system may be manipulated to strengthen immunity to viruses. In HIV virology, researchers are investigating how HIV evolves rapidly to escape the human immune counterattack and at protein pathways that naturally protect some people more than others against HIV. The program in neuroAIDS seeks to find new ways to counter the nerve damage caused by HIV infection that lessens many patients’ ability to think and move. It seeks to create assistive technologies that improve life for those with HIV-associated cognitive disorders through collaboration with the Department of Computer Science. Finally, research on opportunistic infections focuses on developing vaccines and drugs against the likes of Pneumocystis carinii and tuberculosis, infections that prey on AIDS-weakened immune defenses.

D-CFAR grant planning process also identified areas of opportunity, where pilot funding will be focused to drive the collaborations judged most likely to succeed. These were computer modeling and computational studies, optics and nanotechnology and prevention/behavior research.

Despite their world-leading expertise, South African researchers need help in processing “mountains” of under-analyzed data and samples generated by the epidemic. The University of Rochester has an exceptional strength in creating mathematical/computer models of viral reproduction and evolution, immune system responses to viruses and clinical trial outcomes. In addition, researchers here excel in biomedical imaging, nano-optics and optical materials. In cooperation with AIDS researchers, these experts will seek to develop simple diagnostic systems that can be applied "in the field" in South Africa, far from crowded hospitals.

Keefer helped to establish the NIH-sponsored HIV Vaccine Trial Network (HVTN) centers in Africa beginning in 1999. As part of his role with the HVTN Core, he visited African investigators and saw what they could bring to, and take from, a partnership. In particular, he developed relationships with two newly developed HIV Vaccine Trials Units in South Africa, one at the University of Witwatersrand Perinatal HIV Research Unit (UW-PHRU), which is located at the Chris Hani Baragwanath Hospital (CHBH) in Soweto. The other was with the University of Cape Town’s Desmond Tutu HIV Center (UCT-DTHC) in the Nyanga district of Cape Town. Along with HIV vaccine development, both sites are focused on HIV epidemiology and prevention research (particularly in adolescents) and a family-centered approach to HIV care. The PHRU also specializes in research on maternal-pediatric HIV transmission, and the DTHC specializes on the treatment of tuberculosis. All of these areas match closely with research interests in Rochester.

While other African nations may have higher infection rates, no country has more cases than South Africa because of its large population, Keefer said. The country is still largely segregated with large black populations crowded together into areas like the Soweto township and the Nyanga district of Cape Town. Keefer estimates that a significant majority of patients filling the 3,000 beds at CHBH in Soweto are suffering from HIV-related conditions.

In the area of prevention/behavior research, the University of Rochester School of Nursing has already assembled a cadre of investigators that seek to create more effective prevention programs by bringing HIV researchers together with those who study related risk factors (sexual culture, domestic violence, poverty, drug addiction, etc.). The focus within this portion of the D-CFAR will be preventing infection in the populations at highest risk here, globally and especially in Africa. These at-risk populations include adolescent girls, substance-using couples and young black men who have sex with men (MSM).

Stephen Dewhurst, Ph.D., senior associate dean for basic research and professor of Microbiology and Immunology for the University of Rochester School of Medicine and Dentistry, is principal investigator (PI) for the project. Also leading the effort are Lisa M. Demeter, M.D., associate professor of Medicine; Hulin Wu, Ph.D., professor of biostatistics and computational biology, and Dianne C. Morrison-Beedy, Ph.D., APRN, professor and assistant dean for research at the School of Nursing. The effort in Africa will be led by Robin Wood and Linda-Gail Bekker at UCT, and by James McIntyre and Glenda Gray at UW.

The new center begins its work just as the AIDS research community is reacting to the disappointing results in 2007 of a much-anticipated HIV vaccine efficacy trial, the STEP study. The vaccine did not prevent infection or show evidence of slowing the progression of HIV disease.

“While the D-CFAR was submitted well before the vaccine failure, and covers a great many aspects of AIDS research beyond vaccine research, we believe our effort is well timed to be part of a global effort to re-engineer the field of AIDS research,” Dewhurst said. “We need new ideas and this center is designed to generate them.”

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