Temple HIV/AIDS specialist pitches pharma on novel study for patients
In the late 1990s, when doctors began to see unusual health changes in HIV-infected patients, Mary Van den Berg-Wolf, one of the region’s busiest healthcare providers for HIV/AIDS patients, began to investigate solutions.
Researchers soon realized that the high cholesterol levels and changes in body fat distribution were signs of metabolic syndrome, which increases the risk for cardiovascular disease. According to the American Heart Association, metabolic syndrome is marked by obesity in the abdomen, high cholesterol, high blood pressure and insulin resistance.
“The HIV infection itself, as well as the potent new drug therapies, such as protease inhibitors, are at fault,” said Van den Berg-Wolf, associate professor of internal medicine at the School of Medicine.
In non-HIV-infected patients, standard therapy for high cholesterol includes diet, exercise and statins, very effective cholesterol-lowering drugs. Typically, patients start off with a low dose of a statin, increased by the doctor as needed.
But because statins use the same breakdown pathway in the liver as the protease inhibitors, increasing the dose of a statin while the patient is taking protease inhibitors can lead to dangerous side effects. Doctors can prescribe only the lowest statin dose to HIV-infected patients taking protease inhibitors, and that often is not enough to lower the patient’s cholesterol to the recommended levels.
Over the past several years, Van den Berg-Wolf had followed the news about a new drug combination that tested well in non-HIV patients with high cholesterol. It seemed that adding ezetimibe, brand name Zetia, to the statin provided an alternative to upping the statin dose when cholesterol levels had not decreased to the desired goal. In fact, the combination appeared to be more effective than doubling the statin dose.
Yet, it had not been tested in HIV-infected patients. Van den Berg-Wolf began contacting pharmaceutical companies with an idea for a clinical trial and obtained financial support from Abbott Laboratories, which manufactures the protease inhibitor lopinavir/ritonavir, whose brand name is Kaletra.
Van den Berg-Wolf assembled a team of Temple researchers including Ellen Tedaldi, professor of medicine, and Olga Klibanov from the School of Pharmacy. Together, they developed a pilot study to investigate the safety and efficacy of combining ezetimibe and a statin in patients on protease inhibitor therapy who have high cholesterol that hasn’t responded to statin alone. So far, 16 patients are enrolled. Once the study is complete, at the end of this year, a multi-center trial will be conducted to confirm results in a larger population.
High cholesterol and metabolic syndrome are part of a host of health issues that previously were not a concern for HIV/AIDS patients and their physicians because of the disease’s rapid progression and high mortality. Today, however, thanks to protease inhibitors and other new therapies, HIV-infected patients are living normal life spans.
Van den Berg-Wolf emphasizes that it is important for HIV patients to go to their doctors, take HIV medications and follow doctors’ advice.
“Care of the HIV-infected patient has changed dramatically with advances in therapy,” she said. “It has become a treatable, manageable disease and we have to think about long-term health.”
– By Eryn Jelesiewicz