Indication	First Choice	Alternative	Comments/Special Issues
Primary Prophylaxis	N/A	N/A	Primary Prophylaxis indicated for selected HIV-infected adults but not children. Criteria for Discontinuing Primary Prophylaxis: N/A Criteria for Restarting Primary Prophylaxis: N/A
Secondary Prophylaxis (Suppressive Therapy)	Itraconazole oral solution 5–10 mg/kg body weight (maximum 200 mg) per dose by mouth daily	Fluconazole 3–6 mg/kg body weight (maximum 200 mg) by mouth once daily	Secondary Prophylaxis Indicated: Documented histoplasmosis in a patient with impaired immune function Criteria For Discontinuing Secondary Prophylaxis If All of the Following Criteria Are Fulfilled: CD4 percentage >15% at any age; or CD4 cell count >150 cells/mm3 aged ≥6 years. Received ≥1 year itraconazole maintenance therapy Established (e.g., ≥6 months) adherence to effective cART Negative Histoplasma blood cultures Serum Histoplasma antigen <2 ng/mL Use same initial itraconazole dosing for capsules as for solution. Itraconazole solution is preferred to the capsule formulation because it is better absorbed; solution can achieve serum concentrations 30% higher than those achieved with the capsules.
Treatment	Acute Primary Pulmonary Histoplasmosis: Itraconazole oral solution loading dose of 2–5 mg/kg body weight (maximum 200 mg) per dose by mouth 3 times daily for first 3 days of therapy, followed by 2–5 mg/kg body weight (max 200 mg) per dose by mouth twice daily for 12 months. Duration of 12 weeks is sufficient for HIV-infected children, with functional cellular immunity (CD4 percentage >20% or if aged ≥6, CD4 cell count >300 cells/mm3), provided monitoring confirms clinical improvement and decreased urine antigen concentrations. Mild Disseminated Disease: Itraconazole oral solution loading dose of 2–5 mg/kg body weight (maximum 200 mg) per dose by mouth 3 times daily for first 3 days of therapy, followed by 2–5 mg/kg body weight (maximum 200 mg) per dose by mouth twice daily for 12 months Moderately Severe to Severe Disseminated Disease Acute Therapy (Minimum 2-Week Induction, Longer if Clinical Improvement is Delayed, Followed by Consolidation Therapy): Liposomal amphotericin B 3–5 mg/kg body weight, IV once daily (preferred) Amphotericin B deoxycholate 0.7–1 mg/kg body weight IV once daily (alternative) Consolidation Therapy (Followed by Chronic Suppressive Therapy): Itraconazole oral solution initial loading dose of 2–5 mg/kg body weight (maximum 200 mg) per dose by mouth 3 times daily for first 3 days of therapy, followed by 2–5 mg/kg body weight (max 200 mg) per dose by mouth given twice daily for 12 months Central Nervous System Infection Acute Therapy (4–6 Weeks, Followed by Consolidation Therapy): Liposomal amphotericin B, 5 mg/kg body weight IV once daily (AII) Consolidation Therapy (Followed by Chronic Suppressive Therapy): Itraconazole oral solution initial loading dose of 2–5 mg/kg body weight (maximum 200 mg) per dose by mouth 3 times daily for first 3 days of therapy, followed by 2–5 mg/kg body weight (max 200 mg) per dose by mouth given twice daily for ≥12 months and until histoplasma antigen is no longer detected in cerebrospinal fluid	Acute Primary Pulmonary Histoplasmosis: Fluconazole 3–6 mg/kg body weight (maximum 200 mg) by mouth once daily Mild Disseminated Disease: Fluconazole 5–6 mg/kg body weight IV or by mouth (maximum 300 mg) per dose, twice daily (maximum 600 mg/day) for 12 months Moderately Severe to Severe Disseminated Disease: If itraconazole not tolerated, amphotericin alone for 4–6 weeks can be used with monitoring that confirms decline in histoplasma urine and serum antigen levels. Liposomal amphotericin B 3–5 mg/kg body weight IV once daily (preferred) for 4–6 weeks Amphotericin B deoxycholate 0.7–1 mg/kg body weight IV once daily (alternative) for 4–6 weeks	Use same initial itraconazole dosing for capsules as for solution. Itraconazole solution is preferred to the capsule formulation because it is better absorbed; solution can achieve serum concentrations 30% higher than those achieved with the capsules. Urine antigen concentration should be assessed at diagnosis. If >39 ng/mL, serum concentrations should be followed. When serum levels become undetectable, urine concentrations should be monitored monthly during treatment and followed thereafter to identify relapse. Serum concentrations of itraconazole should be monitored and achieve a level of 1 µg/mL at steady-state. Levels exceeding 10 µg/mL should be followed by dose reduction. High relapse rate with CNS infection occurs in adults and longer therapy may be required; treatment in children is anecdotal and expert consultation should be considered. Chronic suppressive therapy (secondary prophylaxis) with itraconazole is recommended in adults and children following initial therapy. Amphotericin B deoxycholate is better tolerated in children than in adults. Liposomal amphotericin B is preferred for treatment of parenchymal cerebral lesions.

Key to Acronyms: cART = combination antiretroviral therapy; CD4 = CD4 T lymphocyte; CNS = central nervous system; IV = intravenous