Safety and efficacy of liposomal amphotericin B compared with conventional amphotericin B for induction therapy of histoplasmosis in patients with AIDS.
BACKGROUND
In patients with moderate to severe histoplasmosis associated with AIDS, the preferred treatment has been the deoxycholate formulation of amphotericin B. However, serious side effects are associated with use of amphotericin B.


OBJECTIVE
To compare amphotericin B with liposomal amphotericin B for induction therapy of moderate to severe disseminated histoplasmosis in patients with AIDS.


METHODS
Randomized, double-blind, multicenter clinical trial.


METHODS
21 sites of the U.S. National Institute of Allergy and Infectious Diseases Mycoses Study Group.


METHODS
81 patients with AIDS and moderate to severe disseminated histoplasmosis.


METHODS
Clinical success, conversion of baseline blood cultures to negative, and acute toxicities that necessitated discontinuation of treatment.


RESULTS
Clinical success was achieved in 14 of 22 patients (64%) treated with amphotericin B compared with 45 of 51 patients (88%) receiving liposomal amphotericin B (difference, 24 percentage points [95% CI, 1 to 52 percentage points]). Culture conversion rates were similar. Three patients treated with amphotericin B and one treated with liposomal amphotericin B died during induction (P = 0.04). Infusion-related side effects were greater with amphotericin B (63%) than with liposomal amphotericin B (25%) (P = 0.002). Nephrotoxicity occurred in 37% of patients treated with amphotericin B and 9% of patients treated with liposomal amphotericin B (P = 0.003).


CONCLUSIONS
Liposomal amphotericin B seems to be a less toxic alternative to amphotericin B and is associated with improved survival.
Division of General Medicine, University of Texas-Houston Medical School, 6431 Fannin, MSB 1.122, Houston, TX 77030, USA. Philip.C.Johnson@uth.tmc.edu
Philip C
PC
Johnson
L Joseph
LJ
Wheat
Gretchen A
GA
Cloud
Mitchell
M
Goldman
Dan
D
Lancaster
David M
DM
Bamberger
William G
WG
Powderly
Richard
R
Hafner
Carol A
CA
Kauffman
William E
WE
Dismukes
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D004311:Double-Blind Method; D006660:Histoplasmosis / Q000188:drug therapy*; D006801:Humans; D008081:Liposomes; D012449:Safety
D000935:Antifungal Agents; D008081:Liposomes; D000666:Amphotericin B