An open-label dose-escalation trial of oral dehydroepiandrosterone tolerance and pharmacokinetics in patients with HIV disease.
Dehydroepiandrosterone (DHEA) is a naturally occurring adrenal steroid reported to have immunomodulatory and antiviral activity in cellular and animal models as well as modest in vitro antiretroviral activity against human immunodeficiency virus (HIV). A phase I dose-escalation study was performed to evaluate the safety and pharmacokinetics of DHEA in subjects with symptomatic HIV disease and an absolute CD4 lymphocyte count between 250 and 600 cells/microliters. Thirty-one subjects were evaluated and monitored for safety and tolerance. The oral drug was administered three times daily in doses ranging from 750 mg/day to 2,250 mg/day for 16 weeks. Some immunological and virological parameters were monitored as well. The drug was well tolerated and no dose-limiting side effects were noted. Dose proportionality was evidenced neither by the serum DHEA nor by DHEA-S time-concentration curves for the three dosing groups. However, the study cohort appeared to consist of two subpopulations with markedly different bioavailability for a given DHEA dose. No sustained improvements in CD4 counts nor decreases in serum p24 antigen or beta-2 microglobulin levels were observed. However, serum neopterin levels decreased transiently by 23-40% at week 8 compared with baseline in all dosing groups. DHEA was well tolerated by patients with mild symptomatic HIV disease; evaluation of this agent for efficacy in HIV disease would require randomized, controlled trials.
Dyner
T S
TS
California Pacific Medical Center, San Francisco.
Lang
W
W
Geaga
J
J
Golub
A
A
Stites
D
D
Winger
E
E
Galmarini
M
M
Masterson
J
J
Jacobson
M A
MA
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000284:Administration, Oral; D000328:Adult; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D015496:CD4-Positive T-Lymphocytes; D003687:Dehydroepiandrosterone / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D019314:Dehydroepiandrosterone Sulfate; D004361:Drug Tolerance; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D019798:Neopterin
D001708:Biopterins; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D019798:Neopterin