TY - JOUR
T1 - Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome
AU - Wheat, Joseph
AU - Hafner, Richard
AU - Wulfsohn, Michael
AU - Spencer, Patricia
AU - Squires, Kathleen
AU - Powderly, William
AU - Wong, Brian
AU - Rinaldi, Michael
AU - Saag, Michael
AU - Hamill, Richard
AU - Murphy, Robert
AU - Connolly-Stringfield, Patricia
AU - Briggs, Necia
AU - Owens, Susan
PY - 1993/4/15
Y1 - 1993/4/15
N2 - 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. Design: A prospective, multicenter, open-label clinical trial, with follow-up for at least 52 weeks. Setting: 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). Patients: 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. Interventions: Itraconazole, 200 mg given orally twice daily. Main Outcome Measures: 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 Two relapses occurred (5%; 95% Cl, 0.5% to 16%), one in a patient withdrawn from the study 18 weeks earlier and one in a patient who did not comply with the study therapy.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 (Cl, 26% to 59%), and serum specimens became negative in 75% of patients (Cl, 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.
AB - 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. Design: A prospective, multicenter, open-label clinical trial, with follow-up for at least 52 weeks. Setting: 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). Patients: 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. Interventions: Itraconazole, 200 mg given orally twice daily. Main Outcome Measures: 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% Cl, 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 (Cl, 26% to 59%), and serum specimens became negative in 75% of patients (Cl, 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.
UR - http://www.scopus.com/inward/record.url?scp=0027467770&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027467770&partnerID=8YFLogxK
M3 - Article
C2 - 8383934
AN - SCOPUS:0027467770
SN - 0003-4819
VL - 118
SP - 610
EP - 616
JO - Annals of internal medicine
JF - Annals of internal medicine
IS - 8
ER -