Phase I/II trial of the anti-HIV activity of mifepristone in HIV-infected subjects ACTG 5200.
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.
Para
Michael F
MF
Ohio State University, Columbus, OH, USA. para.1@osu.edu
Schouten
Jeff
J
Rosenkranz
Susan L
SL
Yu
Song
S
Weiner
David
D
Tebas
Pablo
P
White
C Jo
CJ
Reeds
Dominic
D
Lertora
Juan
J
Patterson
Kristine B
KB
Daar
Eric S
ES
Cavert
Winston
W
Brizz
Barbara
B
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D015735:Mifepristone / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D010919:Placebos / Q000008:administration & dosage; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
D019380:Anti-HIV Agents; D010919:Placebos; D012367:RNA, Viral; D015735:Mifepristone