April 2014

CHOP Researcher Advances Adolescent Care in Africa

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A Children’s Hospital of Philadelphia pediatrician’s research project spans across continents to Botswana, a sub-Saharan African country with a busy clinic for 2,000 HIV-infected children and adolescents who stole her heart.

Elizabeth Lowenthal, MD, MSCE, remembers noticing a remarkable 12-year-old boy in Botswana, “a real leader” who spontaneously sat down and began translating for an American social worker who had recently arrived to organize a camp for patients. Smart and engaging, he did well on antiretroviral therapy until he became an older teenager. He struggled with his adherence, ended up failing his treatment, and became resistant to the medications.

Dr. Lowenthal brought this lesson to CHOP, along with many others that she learned while living for four years in Botswana, where she provided care as the clinical director of the Botswana-Baylor Children’s Clinical Centre of Excellence. She began practicing there in 2004, when the country was just getting antiretroviral treatment. Currently, more than 3 million children worldwide are affected by HIV, and more than 90 percent live in sub-Saharan Africa.

“Lots and lots of people in Botswana are infected, and just about everybody is affected one way or another by HIV,” Dr. Lowenthal said. “Botswana has better resources than most of the countries in sub-Saharan Africa, so figuring out what can work there hopefully can translate to where most of the kids are.”

As one of the only pediatricians at the time treating children with HIV in Botswana, Dr. Lowenthal became involved with government committees that were creating public health policies for the country. The committee members would turn to Dr. Lowenthal for recommendations for the pediatric population with HIV, but she found that there were little data in the literature to guide some of their decisions.

So while her heart was still in Botswana, she returned to the U.S. and began a research fellowship at CHOP to learn how to scientifically approach these questions. Dr. Lowenthal is now an assistant professor of pediatrics at CHOP, a staff physician at the Special Immunology Family Care Center, and lead research physician for CHOP Global Health.

In her first major research publication in the Journal of the American Medical Association, Dr. Lowenthal’s findings supported the use of efavirenz as initial antiretroviral treatment because it was associated with less virological failure when compared to another drug, nevirapine, which is used more commonly in children. The study influenced not only the treatment guidelines in resource-limited settings, such as Botswana, but it also helped to clarify U.S. guidelines.

Most of her current work is focused on adherence to HIV treatments among perinatally HIV-infected adolescents in Africa, a fast-growing population. Good treatment outcomes have allowed more children with HIV to reached young adulthood, and now they face unique challenges. As Dr. Lowenthal described in a recent Lancet Infectious Diseases review paper, they must confront psychosocial issues, negotiate decisions about sexual relationships, and manage a chronic illness during a period of rapid physical and psychological changes.

Unfortunately, this tumultuous time threatens the longevity of their treatment.

“While these treatments are lifesaving and amazing, they only work if you take them consistently,” Dr. Lowenthal said. “If they miss doses for a period of time, they develop resistance to them. Many adolescents, unfortunately, are losing the limited treatment options that they have. If we can’t support adherence well enough, all of these other problems are not going to be relevant because kids aren’t going to continue to survive.”

Her research projects take many perspectives to help predict which adolescents are going to have difficulty with adhering to their medication long-term. Recognizing those children who would most likely benefit from support services could be an important first step to possibly preventing their failure, Dr. Lowenthal said.

An ongoing study is comparing methods that measure adherence to determine which are the most useful among HIV-infected adolescents in Botswana. These methods include self-report, electronic monitoring devices, pill counts, medication refill rate, and monitoring virus suppression. Dr. Lowenthal’s research team also is considering how adolescents’ autonomy over medication is associated with these measurement methods.

In a pilot study published in AIDS Care, her research team evaluated the Pediatric Symptom Checklist (PSC) as a simple screening tool to identify children and adolescents with psychosocial needs. A prospective study is under way to assess whether high scores on the PSC precede adherence problems and treatment failure. Once these psychosocial areas are identified, healthcare providers could use them as starting points for interventions.

“In a setting where you have thousands of kids, trying to figure out what are the big issues that we need to approach is really important,” Dr. Lowenthal said. “They are certainly complex problems that need complex solutions. We are starting with just trying to understand what’s at the root.”

Dr. Lowenthal’s work in Botswana has crossover to her clinical work in the Special Immunology Family Care Center, where she and her team provide treatment for about 150 HIV-infected children. For example, artists at CHOP adapted a book created for children in Botswana to help initiate discussions about their HIV status. In the version for the American children, the good guys are superheroes instead of soldiers, and the kids play basketball instead of soccer, but the message is the same: Taking your antiretroviral medications keeps your body strong.

Dr. Lowenthal keeps in touch with some of her patients in Botswana, and her research allows her to visit two or three times a year. The amazing young man she met during her early years in Africa is now in his twenties and doing better again. Yet, she continues to ask: “What could I have done to have kept him from losing options and struggling during his teenage years?”

A CDC-PEPFAR Public Health Effectiveness Grant funds Dr. Lowenthal’s work, and additional questions related to optimizing adherence measurement and defining developmental and psychosocial factors associated with nonadherence are funded by an NIH K23 Career Development award.

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