OBJECTIVE: To review the pharmacotherapy of disseminated histoplasmosi
s (DH) in patients with AIDS. The article provides an overview of the
pathophysiology, epidemiology, clinical presentation and diagnosis of
this disease. Clinical trials reporting intervention with antifungal t
herapy are reviewed, with an emphasis on efficacy and toxicity of thes
e agents. DATA SOURCES: A MEDLINE search from 1976 to the present was
performed to identify pertinent biomedical literature, including revie
ws. STUDY SELECTION: All available reviews and clinical trials in AIDS
patients were evaluated, as were all available case series and interv
entional clinical trials. DATA SYNTHESIS: DH in patients with HIV infe
ction is an AIDS-defining opportunistic infection caused by Histoplasm
a capsulatum It is most frequently observed in HIV-infected patients l
iving in or traveling to endemic regions. The clinical presentation mo
st often includes fever and weight loss, but may be complicated by com
orbid illness such as other opportunistic infections. Diagnosis is bes
t established by histologic examination of peripheral blood smear or b
one marrow aspirate, or isolation of the organism in cultures of blood
, bone marrow, and respiratory secretions. Serologic examinations may
provide supportive diagnostic information. Detection of histoplasma po
lysaccharide antigen (HPA) in serum or urine may prove to be a promisi
ng approach for the rapid diagnosis and therapeutic monitoring of DH i
n AIDS patients. In contrast to immunocompetent hosts, high relapse ra
tes are reported after therapy in AIDS patients. Therefore, initial (i
nduction) therapy is routinely followed by long-term (maintenance) the
rapy to prevent relapse. Issues regarding the selection, dosage, and d
uration of therapy, as well as prophylaxis of patients at highest risk
, still need to be addressed by controlled clinical trials. CONCLUSION
S: Amphotericin B is presently the drug of choice for induction therap
y. Maintenance therapy with either amphotericin B or an oral azole ant
ifungal agent active against H. capsulatum is necessary to prevent rel
apse. Itraconazole, a triazole antifungal agent may provide effective
alternative therapy for both induction and maintenance treatment of DH
.