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Defining a New Era - HIV/AIDS
Each year in the United States, approximately 150 babies are born with the human immunodeficiency virus (HIV). Approximately 10 percent of these babies are located in the District of Columbia. The nation’s capital has the highest number of HIV/AIDS cases in the United States, with 56,300 new infections in the United States per year. While these statistics are troubling, the District of Columbia provides a unique opportunity for translational research and collaboration through Children’s National.
From the Bench
At the laboratory benches atop Children’s National Medical Center, investigators from the Center for Cancer and Immunology Research collaborate within CRI and around the world to define a new era in medicine by employing the latest technologies in fighting HIV at its very core.
Basic and clinical researcher Steve Zeichner, MD, PhD, of the Center for Cancer and Immunology, uses many tools of molecular biology to study how HIV interacts with its host cells. Zeichner, who also co-directs the Basic Science Core of the George Washington University HIV-AIDS Institute, a partnership of six academic institutions in Washington, DC, dedicated to interdisciplinary research on HIV, seeks to identify factors that cause the virus to either remain latent within its host cells or make new virus. If these factors are identified, physicians may eventually be able to work to deplete the reservoirs of HIV that remain stable within the body for decades.
“Right now there is no cure for HIV because the virus can remain latent within its host cells for many years,” says Zeichner. “Learning how to safely activate HIV from latency probably represents the first step toward finding a way to eliminate HIV from the body.”
In the near future, scientists like Zeichner and his colleagues will examine the inner workings of HIV’s biology and the causes of its devastating side effects, and focus on more effective disease management. Research in the laboratories of Patricio Ray, MD, for example, uses proteomics to detect microscopic changes in the urine of patients who are more likely to suffer from HIV-associated nephropathy (HIVAN), a common form of kidney failure that affects at least 10 percent of HIV-positive African Americans. Eventually, early detection of this devastating disorder might prevent total kidney failure in these patients. Natella Rakhmanina, MD, studies the pharmacology of the numerous drug combinations involved in keeping HIV at bay. Through the Center for Genetic Medicine Research, and collaborations with Eric Hoffman, PhD, scientists seek to identify factors at a genetic level that might reveal a predictable response to specific drug combinations, to help physicians learn how a person’s genetic blueprint could impact a course of treatment.
At the Bedside
Developing more effective social supports for teens with HIV is a large piece of HIV research at Children's National. By providing that support and encouraging teens to share their experiences with each other and their communities, education programs become more effective over time. |
Many HIV researchers at CRI, including Dr. Zeichner, Dr. Rakhmanina, and Larry D'Angelo, MD, MPH, also have a role in the clinical setting. Dr. Rakhmanina directs the Special Immunology Service (SIS) in the Division of Infectious Disease. Approximately 160 HIV infected children up to age 13 are followed through this service. A majority of the service’s pediatric patients have vertically acquired infection (passed from mother to child at birth), often because mothers-to-be may not have access to prenatal care or are not diagnosed until they arrive at the hospital in labor.
The clinic sees patients frequently to monitor the complex drug combinations of at least three drugs taken twice per day. The team must consistently monitor the levels of HIV in the bloodstream and the status of the patient’s immune system, and sometimes adjust the cocktail because the virus develops resistance to the medicines and children may have difficultly sticking to the tough drug regimen. At CRI’s Bioanalytical Lab, a test that quickly monitors the level of drugs in the patient’s blood has been developed under the leadership of Steven Soldin, PhD. Dr. Soldin also pioneered a more efficient test that measures drug levels in a patient’s saliva. While research in this arena is ongoing, testing the concentrations of drugs in the saliva is a faster, non-invasive, and less complicated way for healthcare providers to ensure that pediatric patients are adhering to their treatment and medication schedule and to apply therapeutic drug monitoring in treatment of HIV. It’s possible that future models of the saliva test could be used in countries where repeated blood draws to test for medication compliance is not a sanitary option.
HIV-infected patients between the ages of 13 and 21 are seen at Children’s Burgess Clinic in the Division of Adolescent and Young Adult Medicine directed by Dr. D’Angelo. Celebrating its 20th anniversary in 2008, the Burgess Clinic also sees another 160 patients in a primary care, and often walk-in, setting. The clinic provides medical and social support to adolescents and teens living with HIV, in a more convenient and approachable setting.
Recently the Centers for Disease Control and Prevention recommended that all children over the age of 13 be tested for the HIV virus. The Center for Clinical and Community Research conducted surveys in the Emergency Department (ED) to better understand barriers and challenges to universal HIV testing among adolescents and their guardians, and to evaluate the basic knowledge about HIV among teens. In the fall of 2008, Children’s National will define a new era by becoming the region’s first pediatric facility providing universal oral fluid rapid HIV testing to adolescents in the ED setting.
Children’s National is one of only four centers nationwide that participates in two NIH-funded clinical trials networks, the Adolescent Trials Network (ATN) and the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) networks. Children’s IMPAACT network site, of which Dr. Zeichner is the principal investigator, is a joint effort with Johns Hopkins University and the Washington Hospital Center, where the mothers of HIV-infected babies seen at Children’s National are followed. IMPAACT has more than 20 sites worldwide that enroll patients in a variety of trials to test new drugs for HIV, other infections that can affect children with HIV, and the many complications that accompany HIV disease. ATN’s multicenter national network studies HIV infection in adolescents and conducts clinical trials investigating new HIV drugs and social and behavioral interventions for young adults faced with HIV.
And Into the Community
ATN’s research focuses on engaging the community to define a new era through a behavior change objective. The premise is that a reduction in infection cannot occur without changing the behaviors that facilitate infection in the community. Community organizations are encouraged to take an active role in the advocacy of HIV infection prevention. ATN’s community education and involvement component is one of the only models of its kind funded by the NIH.
One program, Connect to Protect, engages infected teens in telling their transmission story to various community groups. The group collaborates with the DC government to reach high risk populations where they spend their time socially, such as night clubs and other teen hangouts, to interrupt the virus’ transmission. The community is engaged in the research effort for ATN from the beginning, with the hope that it will sustain and grow the effort on its own. ATN also publishes information mapping the city’s epidemic and links crime to current infection and population rates.
A unique feature of the network is its Youth Advisory Board comprised of 8 to 12 HIV-infected youth. This voluntary group meets monthly to review research results, provide recommendations, share stories, and develop strategies to further disseminate the most important messages into the community.
Defining a New Era in HIV Research
From bench to bedside, and out into the larger community, HIV research at Children’s National is united by the premise that, sooner rather than later, interventions can effectively treat HIV disease, stop its spread, and ultimately, this virus will no longer represent a death sentence for hundreds of thousands of people every year.
Through a federal NIH grant Children's National is a primary site for the ATN for HIV/AIDS interventions. The ATN team conducts both clinical research and a community education program for leaders, families, and teens in the Washington, DC area. The team includes doctors, nurses, community educators, volunteers, and social workers. |
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