Phase I/II Trial of the Anti-HIV Activity of Mifepristone in HIV-Infected Subjects ACTG 5200
Year: 2010
Type: article
Abstract: BACKGROUND: Mifepristone is a glucocorticoid receptor inhibitor shown in vitro to have anti-HIV activity and anti-simian immunodeficiency virus activity in a macaque model. A phase I/II trial was performed to assess the drug's safety and anti-HIV activity. METHODS: A 28-day double-blind, placebo-controlled trial of mifepristone at doses of 75 mg, 150 mg, and 225 mg given daily was conducted in HIV+ persons with CD4+ lymphocyte counts >or=350 cells per cubic millimeter who had no recent antiretroviral therapy. RESULTS: Fifty-six male and 1 female subjects with a median entry CD4+ lymphocyte count of 555 cells per cubic millimeter and plasma HIV-1 RNA of 15,623 copies per milliliter were accrued. Forty-five subjects (78.9%) were available for endpoint analysis. In each arm, changes from baseline to day 28 in plasma HIV-1 RNA and CD4+ lymphocyte count were not significantly different from zero (no change). There was no relationship between mifepristone trough concentrations and plasma HIV-1 RNA. Day 28 morning plasma cortisol levels were significantly higher in the 150 mg and 225 mg arms compared with placebo, confirming biologic activity, and returned to baseline by day 56. Serum lipids did not change during the trial. Fasting blood sugar was 2.5 mg/dL higher on day 28 in the mifepristone arms, but the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) did not change. Three subjects (7.3%) receiving mifepristone developed a grade 2 rash. CONCLUSIONS: Mifepristone at doses of 75-225 mg daily was safe and well-tolerated, but did not show significant anti-HIV activity.
Institutions: University of North Carolina at Chapel Hill, The Ohio State University, University of California, Los Angeles, The Lundquist Institute, University of Washington, Harbor–UCLA Medical Center, University of Minnesota, Harvard University, Social and Scientific Systems (United States), University of Pennsylvania, Washington University in St. Louis, Tulane University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1050281965, G115468880, G1214792496, G1346130624, WASHINGTON UNIVERSITY AIDS CLINICAL TRIALS UNIT, G1944963898, G2027736814, G2074353153, G2127051194, G2135258891, G251702431, ADULT AIDS CLINICAL TRIALS UNIT, G3277483280, G3483687112, G374818150, UW Clinical HIV Integrated Research Program, G4553935269, G4649361189, G488872913, G5268332287, G5963541913, G6192409956, G650174051, G6643580741, AIDS CLINICAL TRIALS UNIT, G7879357720, G8083914350, G8469846177, G857487509, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections, Statistical and Data Management Center (SDMC), Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG), The University of North Carolina Center for AIDS Research, University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit, G936311976, G961682679
OpenAlex ID: W2004511586