Background: Histoplasmosis is the most common endemic mycosis among people living with advanced HIV infection. Purpose: Describe general aspects and challenges of this disease and its association with HIV. Research Design: Review of literature. Study Sample: Articles found using different combinations of terms including “disseminated histoplasmosis” and AIDS/HIV or immunosuppression in PubMed, Scopus, WHO Global health library, and Scielo database. Analysis: We look for information on epidemiology, pathogenesis, diagnosis, and treatment of histoplasmosis in AIDS patients. Results: Histoplasmosis is caused by Histoplasma capsulatum, a dimorphic fungus encountered throughout the world, mainly in soil enriched with bat and bird excreta. Progressive disseminated histoplasmosis is the main presentation of this mycosis in people living with advanced HIV and is fatal if left untreated. Symptoms include a systemic disease characterized by fever, weight loss, night sweats, skin manifestations, hepatomegaly, splenomegaly, and septic shock. Diagnostic tests include culture, visualization of H. capsulatum by direct and histopathological examination, serology, antigen, molecular, and skin testing. Patients with disseminated disease require aggressive and prolonged treatment to eradicate the pathogen and include amphotericin B and itraconazole. In many low income countries of endemic regions, histoplasmosis in HIV-positive patients is often undiagnosed or misdiagnosed as another opportunistic infection, due to the similarity in clinical manifestations and to the paucity of better diagnostic tests. Conclusion: Histoplasmosis remains a neglected disease. Few studies about the disease and expensive treatments make it difficult to reduce the morbidity and mortality of this condition. Public health services and physicians must be aware of histoplasmosis' burden among the HIV-positive population.

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