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COMMON HERPES MEDICATION REDUCES HIV-1 LEVELS, INDEPENDENT OF HERPES INFECTION Case Western Reserve University (CWRU) researchers are part of an international team that has discovered that a common herpes drug reduces HIV-1 levels — even when patients do not have herpes. Published online in Clinical Infectious Diseases, the finding rebuts earlier scien - tific assumptions that valacyclovir (Valtrex) required the presence of herpes to benefit patients with HIV-1. The result not only means that valacy - clovir can be used effectively in a broader range of HIV-1 patients, but also suggests promising new avenues for the develop- ment of HIV-fighting drugs. This insight is particularly significant, given that some forms of HIV-1 have become resistant to existing medications. "The results demonstrated that the mechanism by which valacyclovir acts against HIV is not only through the pres - ence of Herpes simplex virus 2 (HSV-2)," says Senior Author Benigno Rodriguez, MD, Associate Professor of Medicine and Infectious Diseases, CWRU School of Medicine, Co- principal Investigator, CWRU/University Hospitals (UH) Case Medical Center AIDS Clinical Trials Unit, and infectious disease specialist with UH Case Medical Center. Even better, Rodriguez says, studies by these groups helped illumi - nate exactly how the medication decreases HIV-1 levels. Valacyclovir is activated in virus-infected cells and then blocks the ability of HIV to reproduce. The result? Reduced viral load. "Our most recent clinical study demonstrates that valacyclovir blocks HIV replication directly," says Michael M. Lederman, MD, also a senior author and Scott R. Inkley Professor of Medicine, CWRU School of Medicine, Principal Investigator of the CWRU/UH Case Medical Center AIDS Clinical Trials Unit and infectious disease specialist with UH Case Medical Center. "The anti-HIV activity of valacyclovir does not depend on blocking the inflammation caused by HSV-2," Drs. Lederman and Rodriguez, the two Cleveland-based members of the research team, believe that data from this study can inform new drug development. Essentially, researchers would try to design agents based on valacyclovir's molecular structure — now proven to block HIV activity. This research was supported, in part, by the Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health (NIH), the NIH Bench- to-Bedside Program and by federal funds from the National Cancer Institute. METABOLITE OF PROSTATE CANCER DRUG MORE EFFECTIVE AT TREATING AGGRESSIVE TUMORS Cleveland Clinic researchers have discov- ered for the first time that a metabolite of an FDA-approved drug for metastatic pros- tate cancer, abiraterone (Abi), has more anti-cancer properties than its precursor. The research was published online June 1 in Nature. Cleveland Clinic researcher Nima Sharifi, MD, found that Abi, a steroid inhibi - tor, is converted into the more physiologi- cally active D4A (4-abiraterone) in both patients and animal models who take the drug for prostate cancer. Furthermore, they found that D4A is more effective than Abi at killing aggressive prostate cancer cells, suggesting that some patients may benefit from direct treatment with D4A. Prostate cancer cells are fueled by androgens. When prostate cancer spreads, androgen deprivation therapy is used to cut off the tumor's energy supply. However, aggressive, metastatic tumors can become resistant to this type of therapy. In a landmark 2013 publication in Cell, Dr. Sharifi described a genetic mutation that enables prostate cancer cells to produce their own hormones for fuel, making them resistant to traditional hormone deprivation therapies. Abi works by blocking CYP17A1, an enzyme crucial for the production of androgens. Dr. Sharifi's team found that the more active D4A inhibits two additional enzymes responsible for producing androgens and blocks the androgen receptor, which renders existing androgens inac - tive. They found that 12 patients on active Abi therapy had detectable Benigno Rodriguez, MD Michael M. Lederman, MD Nima Sharifi, MD RECENT RESEARCH +++++++++++++++++ + +++ + +++ +++++++++++++++++ RESEARCH ❯ 2 2 | Cleveland/Akron/Canton MD NEWS ■ M D N E W S . CO M ■ J U LY/AU G U S T 2 0 1 5