Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

Histoplasmosis

Last Updated: September 13, 2019; Last Reviewed: September 13, 2019

Recommendations for Preventing and Treating Histoplasma capsulatum Infections
Preventing First Episode of Histoplasma capsulatum Infection (Primary Prophylaxis)
Indications for Initiating Primary Prophylaxis:
  • CD4 count <150 cells/mm3 and at high risk because of occupational exposure or residence in a community with a hyperendemic rate of histoplasmosis (>10 cases/100 patient-years) (BI)
Preferred Therapy:
  • Itraconazole 200 mg PO once daily (BI)
Criteria for Discontinuing Primary Prophylaxis (BIII):
  • Patient on ART, and
  • CD4 count ≥150 cells/mm3, and
  • Undetectable HIV-1 viral load for 6 months
Indication for Restarting Primary Prophylaxis:
  • CD4 count <150 cells/mm3 (BIII)
Treating Moderately Severe to Severe Disseminated Disease
Induction Therapy
Preferred Therapy:
  • Liposomal amphotericin B at 3 mg/kg IV daily (AI)
Alternative Therapy:
  • Amphotericin B lipid complex at 5 mg/kg IV daily (AIII)
Duration:
  • For ≥2 weeks or until clinically improved
Maintenance Therapy
Preferred Therapy:
  • Itraconazole 200 mg PO three times a day for 3 days, then two times a day for ≥12 months (AII), with dosage adjustment based on interactions with ART and itraconazole serum concentration
Treating Less Severe Disseminated Disease
Induction and Maintenance Therapy
Preferred Therapy:
  • Itraconazole 200 mg PO three times a day for 3 days, then 200 mg PO two times a day for ≥12 months (AII), with dose adjustment based on interactions with ART and itraconazole serum concentration
Alternative Therapy:
  • Note: These recommendations are based on limited clinical data for patients who are intolerant to itraconazole and who are only moderately ill.
  • Posaconazole, extended release tablet 300 mg PO twice daily for 1 day, then 300 mg PO once daily (BIII)
  • Voriconazole 400 mg PO twice daily for 1 day, then 200 mg PO twice daily (BIII)
  • Fluconazole 800 mg PO once daily (CII)
Treating Histoplasma Meningitis
Induction Therapy (4–6 Weeks):
  • Liposomal amphotericin B 5 mg/kg IV daily (AIII)
Maintenance Therapy:
  • Itraconazole 200 mg PO two or three times a day for ≥12 months and until resolution of abnormal CSF findings with dosage adjustment based on interactions with ART and itraconazole serum concentration (AIII)
Alternative Therapy:
  • Note: These recommendations are based on limited clinical data for patients intolerant to itraconazole.
  • Voriconazole 400 mg PO two times a day for 1 day, then 200 mg PO two times a day (BIII)
  • Posaconazole 300 mg extended release tablet PO twice daily for 1 day, then 300 mg PO once daily (BIII)
  • Fluconazole 800 mg PO once daily (CII)
Long Term Suppressive Therapy
Indications:
  • Severe disseminated or CNS infection after completing ≥12 months of treatment (AIII), and
  • Relapse despite appropriate initial therapy (BIII)
Preferred Therapy:
  • Itraconazole 200 mg PO once daily (AIII)
Alternative Therapy:
  • Posaconazole 300 mg extended release tablet PO once daily (BIII)
  • Voriconazole 200 mg PO twice daily (BIII)
  • Fluconazole 400 mg PO once daily (CII)
Criteria for Discontinuing Long Term Suppressive Therapy (AI):
  • Received azole treatment for >1 year, and
  • Negative fungal blood cultures, and
  • Serum or urine Histoplasma antigen below the level of quantification, and
  • Have an undetectable HIV viral load, and
  • CD4 count >150 cells/mm3 for ≥6 months in response to ART
Indication for Restarting Secondary Prophylaxis:
  • CD4 count <150 cells/mm3 (BII)
Other Considerations
  • Itraconazole serum concentrations should be measured in all patients after 2 weeks of therapy (time it usually takes to reach steady state) to ensure adequate absorption and to assess changes in hepatic metabolism due to drug interactions (AIII). Random serum concentrations (itraconazole plus hydroxyitraconazole) should be between 1 to 2 µg/mL. Concentrations >4 µg/mL are associated with increased frequency and severity of adverse effects.
  • Itraconazole oral solution is preferred over the capsule formulation because of improved absorption but is less well tolerated. However, it is not necessary to use the oral solution if itraconazole concentration is >1.0 µg/mL with the capsule formulation.
  • Voriconazole trough serum levels should be measured after 5 days of therapy (time it usually takes to reach steady state) with a goal of achieving a concentration of 2 to 5 ug/mL. Levels are highly variable among patients, and for individual patients, levels can vary because of drug-drug interactions. Neurotoxicity and hepatotoxicity are associated with serum levels >5 ug/mL, but individual patients can experience adverse effects with lower serum levels.
  • Trough posaconazole serum levels should be measured after 5 days of therapy (time it usually takes to reach steady state) to ensure adequate absorption, with a goal of achieving a concentration >1 ug/mL.
  • Acute pulmonary histoplasmosis in patients with HIV with CD4 count >300 cells/mm3 should be managed the same as in immunocompetent patients (AIII).
  • All triazole antifungals have the potential to interact with certain ART agents and other anti-infective agents. These interactions are complex and can be bidirectional. Drug-Drug Interactions in the Adult and Adolescent Antiretroviral Guidelines lists these interactions and recommends dosage adjustments where feasible.

Key: ART = antiretroviral therapy; CD4 = CD4 T lymphocyte cell; CNS = central nervous system, CSF = cerebrospinal fluid; CYP = cytochrome P450; IV = intravenous; PI = protease inhibitor; PO = orally

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