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Novel HIV drug to be studied in cell cultures and patients

November 23, 2015

A second project addresses immune mechanisms, investigating whether clinical depression makes a person's immune cells more vulnerable to HIV infection. The researchers will also study how aprepitant may have a dual effect, both preventing HIV from entering cells and restoring the immune function of natural killer cells. People with depression show lower levels of natural killer cells, and NK1R drugs may act against depressive behavior. Douglas leads this project, working with co-investigators Jordan Orange, M.D., Ph.D., of Children's Hospital, an expert in natural killer cells, and Dwight Evans, M.D., chair of Psychiatry at the Penn School of Medicine. Evans is internationally prominent for studying the connections between depression and immune function.

The third project is a Phase 1B clinical trial, to be led by Pablo Tebas, M.D., clinical research site principal investigator of the AIDS Clinical Trials Unit at the Hospital of the University of Pennsylvania. That unit participates in IMPAACT--the International Maternal Pediatric Adolescent AIDS Clinical Trials Group, of which Douglas is the overall principal investigator for IMPAACT's Philadelphia Clinical Trials Unit.

The trial, to be conducted in HIV-infected adult patients already receiving antiretroviral medicines, will test the safety of aprepitant in those patients. A second clinical study will test aprepitant as an antiviral agent in combination with ritonavir, another anti-HIV drug, in patients failing HIV therapy. The interactions between both drugs may strengthen the effects of aprepitant without increasing its dosage. The trial will measure antiviral activity as well as changes in depressive behavior and anxiety among the subjects.

Although aprepitant has a central role in the study projects, it may not ultimately be the drug used in future HIV clinics. "Aprepitant is the only FDA-approved drug among NK1R antagonists, but we expect that ultimately another compound in the same class will become a new anti-AIDS drug," says Florin Tuluc, M.D., Ph.D., of Children's Hospital, an expert on cell signaling who is a collaborator in the program. "We believe a NK1R antagonist will have an important role as a novel medicine in treating neuroAIDS."

Source: Children's Hospital of Philadelphia