Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens.
Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14.
A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82).
One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.

The burden of histoplasmosis has been poorly documented in most of the endemic areas for the disease, including Brazil. Also, modern non-culture-based diagnostic tests are often non-available in these regions. This was a prospective cohort study in HIV-infected patients with suspected disseminated disease evaluated with different diagnostic tests. Patients were enrolled in three referral medical centres in Porto Alegre, Brazil. Among 78 evaluated patients, disseminated histoplasmosis was confirmed in eight individuals (10.3%) by the means of classical (culture/histopathology) tests. Antigen detection in the urine was found to be more sensitive: IMMY® ALPHA ELISA detected 13 positive cases (16.7%) and the in-house ELISA test developed by the Centers for Disease Prevention and Control (CDC) detected 14 (17.9%). IMMY® and CDC tests provided concordant results in 96.2% of cases. This is the first study to compare the performance of the in-house CDC ELISA test with the IMMY® commercial test for the diagnosis of histoplasmosis, and a high degree of concordance was observed. The study revealed that H. capsulatum is an important agent of disseminated disease in AIDS patients in Brazil, reinforcing the importance of making available modern diagnostic tests as well as safer antifungal agents for the treatment of histoplasmosis.