Phase I/II trial of the anti-HIV activity of mifepristone in HIV-infected subjects ACTG 5200.

TitlePhase I/II trial of the anti-HIV activity of mifepristone in HIV-infected subjects ACTG 5200.
Publication TypeJournal Article
Year of Publication2010
AuthorsPara MF, Schouten J, Rosenkranz SL, Yu S, Weiner D, Tebas P, C White J, Reeds D, Lertora J, Patterson KB, Daar ES, Cavert W, Brizz B
Corporate AuthorsACTG A5200 Team of the ACTG
JournalJ Acquir Immune Defic Syndr
Volume53
Issue4
Pagination491-5
Date Published2010 Apr 1
ISSN1944-7884
KeywordsAdult, Anti-HIV Agents, CD4 Lymphocyte Count, Double-Blind Method, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Mifepristone, Placebos, RNA, Viral, Treatment Outcome, Viral Load, Young Adult
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.

DOI10.1097/QAI.0b013e3181d142cb
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID20130470
PubMed Central IDPMC3477637
Grant List1 U01 A1 69494-01 / / PHS HHS / United States
5 P30-AI-045008-07 / AI / NIAID NIH HHS / United States
AI 069434 / AI / NIAID NIH HHS / United States
AI069424-01 / AI / NIAID NIH HHS / United States
AI069474 / AI / NIAID NIH HHS / United States
AI27661 / AI / NIAID NIH HHS / United States
AI68634 / AI / NIAID NIH HHS / United States
AI68636 / AI / NIAID NIH HHS / United States
AI69423-01 / AI / NIAID NIH HHS / United States
AI69495-01 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
RR00046 / RR / NCRR NIH HHS / United States
U01 AI069423 / AI / NIAID NIH HHS / United States
U01 AI069474 / AI / NIAID NIH HHS / United States
U01-AI 032783-13 / AI / NIAID NIH HHS / United States