PHARMACOTHERAPY OF DISSEMINATED HISTOPLASMOSIS PATIENTS WITH AIDS

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 .