Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome.
OBJECTIVE
To assess the efficacy and safety of itraconazole in preventing relapse of histoplasmosis after induction therapy with amphotericin B in patients with the acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis.


METHODS
A prospective, multicenter, open-label clinical trial, with follow-up for at least 52 weeks.


METHODS
Tertiary care hospitals participating in a clinical investigation sponsored by the National Institutes of Allergy and Infectious Diseases (AIDS Clinical Trial Group and Mycoses Study Group).


METHODS
Forty-two patients with AIDS who had successfully completed induction therapy for disseminated histoplasmosis amphotericin B, at least 15 mg/kg body weight given over 4 to 12 weeks.


METHODS
Itraconazole, 200 mg given orally twice daily.


METHODS
Response to therapy, specifically prevention of histoplasmosis relapse, was the main outcome measure. Secondary end points were survival and the effect of therapy on Histoplasma capsulatum variety capsulatum antigen levels in urine and serum. Plasma itraconazole concentrations were measured to document drug absorption and compliance with therapy.


RESULTS
The median follow-up was 109 weeks, and median survival was 98 weeks. Two relapses occurred (5%; 95% CI, 0.5% to 16%), one in a patient withdrawn from the study 18 weeks earlier and one in a patient who did not comply with the study therapy. Patients with elevated antigen levels at study entry showed clearance of antigen from urine and serum; urine specimens became negative in 43% of patients (CI, 26% to 59%), and serum specimens became negative in 75% of patients (CI, 56% to 94%). Only one patient discontinued treatment because of itraconazole toxicity (hypokalemia).


CONCLUSIONS
Itraconazole, 200 mg twice daily, is safe and effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. Antigen clearance from blood and urine correlates with clinical efficacy.
Indiana University School of Medicine, Wishard Memorial Hospital, Indianapolis 46202-2879.
J
J
Wheat
R
R
Hafner
M
M
Wulfsohn
P
P
Spencer
K
K
Squires
W
W
Powderly
B
B
Wong
M
M
Rinaldi
M
M
Saag
R
R
Hamill
R
R
Murphy
P
P
Connolly-Stringfield
N
N
Briggs
S
S
Owens
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000666:Amphotericin B / Q000627:therapeutic use; D000935:Antifungal Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D000946:Antigens, Fungal / Q000378:metabolism; D005260:Female; D006658:Histoplasma / Q000276:immunology; D006660:Histoplasmosis / Q000188:drug therapy*; D006801:Humans; D017964:Itraconazole; D007654:Ketoconazole / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011446:Prospective Studies; D012008:Recurrence
D000935:Antifungal Agents; D000946:Antigens, Fungal; D017964:Itraconazole; D000666:Amphotericin B; D007654:Ketoconazole