The AIDS Clinical Trials Unit (ACTU) at Washington University School of Medicine in St. Louis has received a $10 million grant to find new treatments for AIDS and HIV-related complications, such as dementia, neuropathy and cardiovascular disease. The seven-year grant is from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH).
“AIDS is no longer an automatic death sentence but often can be managed as a chronic disease,” says David B. Clifford, M.D., director of the ACTU and the Melba and Forest Seay Professor of Clinical Neuropharmacology in Neurology. “With current drugs, many HIV patients live for 20 or more years in good health. But standard drugs are not effective in all patients and many develop complications of their disease. Our focus is on developing better treatments with fewer side effects.”
The grant will fund studies to investigate new therapies for patients recently diagnosed with HIV, as well as treatments for patients who have developed resistance to standard HIV medications. The latter includes clinical trials evaluating drugs called CCR5 blockers, which are designed to work differently from current HIV/AIDS drugs. Rather than fighting HIV inside white blood cells, the new drugs prevent the virus from entering cells by blocking its typical entry route, the CCR5 co-receptor.
Washington University researchers will also be assessing new therapies for HIV-related dementia and memory loss. So-called neuroAIDS affects at least one in five people with HIV and has become more common as patients live longer, says Clifford, who also leads the NIH Neurologic AIDS Research Consortium. The virus reaches the brain soon after infection, but few HIV drugs can penetrate the brain to attack the virus. As part of a multi-center trial, the ACTU will be evaluating whether certain drugs known to penetrate the blood-brain barrier, including the antibiotic minocycline, can protect brain cells from HIV damage.
An estimated one-third of patients with HIV experience peripheral neuropathy that is caused either by the virus itself or by the drugs used to treat the virus. Symptoms often cause great discomfort and can include burning, stiffness, prickling, tingling or numbness in the toes and soles of the feet. The ACTU is addressing this problem as a high priority. Dr. Clifford’s group is currently engaged in a clinical trial investigating whether the topical application of high-potency capsaicin applied to the feet can control the pain associated with neuropathy. Capsaicin is an ingredient found in hot chili peppers, and evidence suggests that the chemical can deaden the nerve endings where the pain originates.
While current HIV therapy typically improves immune function and dramatically reduces the amount of the virus circulating in the blood, in some instances, the patient’s immune system never fully recovers from the virus’s initial assault. In these cases, levels of CD4 immune cells remain low, leaving patients susceptible to infections, such as pneumonia, and to certain cancers. ACTU researchers are currently evaluating whether growth factors can stimulate CD4 cells and revive the full function of the immune system.
“We also want to determine which patients are at risk for this complication — is there something specific about the strain of the virus that keeps CD4 levels low or could the genetic makeup of the patient have a role?” asks Clifford.
As patients with HIV live longer, doctors have found that both the disease and its treatment can increase the risk of cardiovascular disease. Researchers have found that levels of HDL (good) cholesterol drop in patients infected with HIV, even before treatment begins. Standard HIV drug therapy also has been shown to have adverse effects on levels of lipids and good cholesterol. The new funding will aid research to identify patients at high risk for cardiovascular disease and HIV drug combinations that could help reduce that risk.
The ACTU also is a collaborator in international studies of AIDS patients, including research to identify the most effective therapies for strains of HIV that are more common in Asia, South America and Africa. These subtypes of the virus differ significantly from those found in patients in the United States and may require different combinations of drugs, Clifford says.
Washington University’s ACTU is part of a national network of clinical trials units, known collectively as the AIDS Clinical Trials Group. Each year the group has enrolled 3,500 to 4,000 new patients in studies to evaluate new drugs for AIDS or complications of the disease. For more information about clinical trials available at the Washington University ACTU, please call (314) 454-0058.
Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.