Penn CFAR co-directors James Hoxie, MD, and Ronald Collman, MD
Celebrating the Perelman School of Medicine’s 250 years has us looking back at some of the great accomplishments and milestones from all corners of the campus, as well as those that have come out of the longstanding collaborations with our partners—many of whom are just next door. Take the
Penn Center for AIDS Research (CFAR), which encompasses over 160 researchers from Perelman, as well as 12 other schools within the University of Pennsylvania, along with The Children’s Hospital of Philadelphia and the Wistar Institute.
One of 19 NIH-funded CFAR sites nationwide, the Penn CFAR just had its 15 year anniversary as a designated National Institutes of Health (NIH) CFAR site, a year also marked with a five-year renewal grant from the NIH worth $13.4 million to continue innovative research in HIV/AIDS.
“The CFAR creates an environment that fosters communication, collaboration and synergy among the members. As a result, Penn, CHOP and Wistar researchers have contributed to many of the most important advances in the HIV/AIDS field over the past decade and a half,” said James Hoxie, MD, professor of Medicine at Penn and director of the Penn CFAR. “This award will allow us to continue that momentum, to explore promising new directions to combat the epidemic, and to help foster a new generation of investigators that will lead to breakthroughs in the future.”
Established in 1999, CFAR supports programs that emphasize interdisciplinary collaboration that can lead to new ways of thinking and breakthrough research, especially collaborations between basic researchers, clinical investigators, and behavioral scientists.
“In the past 15 years, during the CFAR’s three previous funding cycles, we have developed strong infrastructure, proactive leadership, and a rich environment of interdisciplinary HIV/AIDS science,” said Ronald G. Collman, MD, professor of Medicine in the division of Pulmonary, Allergy and Critical Care and co-director of the Penn CFAR. “We’ll continue to develop and lead new initiatives in cutting-edge areas that address national priorities for HIV research.”
Pioneering Research
Many important advances in HIV/AIDS can be traced back to investigators at the Penn CFAR.
Critical basic research to understand how HIV enters cells was carried out at Penn, including identification of a key molecule on T cell surfaces called CCR5 that the virus uses as an entry pathway. The discovery that a rare mutation in CCR5 provides natural resistance to HIV infection came from the lab of Robert Doms, MD, PhD in the 1990s, then a professor of Microbiology at Penn and now Chief of Pathology at CHOP, and his colleagues. This pathway is now being taken a step further by Penn CFAR investigators in efforts focused on achieving a cure, by disrupting CCR5. Using technology that can create mutations similar to the natural CCR5 mutation, a team of researchers led by Carl H. June, MD, professor of Pathology & Laboratory Medicine, Bruce L. Levine, PhD, associate professor of Pathology & Laboratory Medicine, and Pablo Tebas, MD, professor of Medicine in the Division of Infectious Diseases, have used a new technology called “zinc fingers” to mutate this molecule in T cells from infected people. In their landmark study published in March 2014 in the New England Journal of Medicine, they successfully engineered the immune cells of 12 HIV positive patients, found that the CCR5-modified T cells persisted, and that it led to reduced viral loads in some patients when treatment was discontinued.
Another CFAR researcher working towards cure of HIV/AIDS is Luis J. Montaner, DVM, DPhil, director of Wistar’s HIV-1 Immunopathogenesis Laboratory, using strategies to boost the immune system. His group published a groundbreaking clinical study in 2013 showing that treatment with Pegylated Interferon causes a dramatic decrease in the amount of HIV in patients off antiretroviral therapy. That study has led to the initiation of a large randomized clinical trial that just opened, being done in collaboration with Jay R. Kostman, MD, professor of Clinical Medicine in Penn’s division of Infectious Disease. Researchers believe that Pegylated Interferon can help eliminate viral reservoirs, or the so-called hidden HIV, and aid progress towards eradication of the virus or cure. One of the most challenging needs is measuring the viral reservoir, and work led by Una O’Doherty, MD, PhD, associate professor of Pathology and Laboratory Medicine at Penn, has opened new avenues in detecting residual virus.
Beatrice H. Hahn, MD, at the Gombe Stream Research Center in Tanzania
In 2011, two prominent HIV researchers who have contributed to nearly every aspect of HIV research,
Beatrice H. Hahn, MD and George M. Shaw, MD, PhD, joined the Perelman School of Medicine faculty and the Penn CFAR. Among their many contributions, Dr. Hahn, now a member of the Institute of Medicine, in 1999 discovered where HIV originally came from - a related virus infecting chimpanzees in Africa that crossed into humans in 1999. Dr. Shaw discovered that HIV replicates rapidly and to high levels even during the period when people have no symptoms. Since their arrival at Penn, they have described molecular traits for HIV strains that are most efficiently transmitted from person to person—insights that will likely guide the development of vaccines.
Philip R. Johnson, MD, chief scientific officer and executive vice president of CHOP and director of the CHOP Research Institute, and his team developed an innovative gene transfer technology in 2009 that protects monkeys from infection by simian immunodeficiency virus, or SIV, a virus closely related to HIV that causes AIDS in rhesus monkeys. This strategy uses gene transfer to introduce an antibody that attaches to the virus and prevents infection. The technique has moved into human clinical trials, and could ultimately lead to a novel HIV vaccine.
Near and Far
Permanent Secretary of Botswana’s Ministry of Health Dr. Kolaatamo C.S. Malefho and director of the Botswana-UPenn Partnership Harvey Friedman, MD
CFARs throughout the country also support international and domestic populations hit hardest by the epidemic.
For over a decade, Penn CFAR has worked with the Botswana-UPenn Partnership, through the CFAR International Core, directed by Harvey Friedman, MD, which was established to expand Penn’s involvement in international medicine and promote research focused on critical HIV questions in sub-Saharan Africa. Penn CFAR’s International Core supports over 10 research projects in Botswana.
In Philadelphia, many people are unaware of their HIV status, and transmission remains far too high in many groups. New ways to improve testing and prevention are being developed through use of an HIV Mobile Clinical Trials Unit, spearheaded by David S. Metzger, PhD, director of the Social and Behavioral Sciences Core of the CFAR. Introduced into the community in the mid-2000s, the mobile research and HIV testing infrastructure allows Penn researchers and clinicians to go to the communities where the virus is most prevalent and where new infections are most common. The project has also proven successful in enlisting and retaining participants from those communities in research studies. Retention rates, crucial for completing studies with rigor and precision, are at 80 to 90 percent.
While CFAR is dedicated to research on new ways to prevent, treat and cure the disease, its members work closely with clinicians who provide care to people affected by HIV/AIDS. Altogether, Penn CFAR clinicians provide care to nearly 4,000 of HIV patients in the Philadelphia area. CFAR investigators also work closely with HIV/AIDS caregivers at many other key centers in Philadelphia, including other hospital-based providers, and community-based centers including Philadelphia FIGHT.
CFAR also has an active Community Advisory Board (CAB), whose mission is to foster communication between HIV/AIDS researchers in the CFAR and members of affected communities. The CAB has carried out many community-based HIV education and prevention programs and each year sponsors a high-profile event, hosted at City Hall and attended by hundreds of community members and community, religious, and political leaders, honoring important local contributors in the fight against AIDS.
CFAR supports research in all areas of HIV/AIDS research, but in the last year has targeted three specific areas to better address HIV: HIV and substance use; HIV and viral hepatitis; and HIV eradication and functional cure. In addition, the CFAR supports strong interdisciplinary research efforts in HIV in children and adolescents; HIV and women; neurocognitive problems in HIV infection; challenges of HIV in sub-Saharan Africa; and bringing emerging technologies in engineering to bear on AIDS-related needs.
Many of these Penn CFAR’s research milestones and faculty, who have been engaged since the early to mid-80s when HIV/AIDS research began, will be featured in the upcoming 250th anniversary book for the Perelman School of Medicine set to publish this spring.
“We’ve come a long way, but the battle is far from over,” said Hoxie, who also serves as the principal investigator of the grant. “Continued funding for HIV/AIDS research is essential in order to make further progress and improve the lives of those living with HIV or at risk for HIV, here in Philadelphia and in other parts of the world.”