The AIDS Clinical Trials Unit (ACTU) at the School of Medicine 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,” said 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 investigations of 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.
University researchers also will assess 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, said 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 evaluate 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 caused by either the virus or by the drugs used to treat it. Symptoms often cause great discomfort and can include burning, stiffness, prickling, tingling or numbness in the toes and soles of the feet. Addressing this problem as a high priority, Cliford’s group is 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. Evidence suggests that capsaicin, found in hot chili peppers, 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’ 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 evaluating whether growth factors can stimulate CD4 cells and revive the full function of the immune system.
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 to find HIV drug combinations that could help reduce that risk.