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

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.

Invasive Mycoses

Histoplasmosis

Last Updated: May 7, 2013; Last Reviewed: June 14, 2017

Recommendations for Preventing and Treating Histoplasma capsulatum Infections
Preventing 1st 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 living in a community with a hyperendemic rate of histoplasmosis (>10 cases/100 patient-years) (BI)
Preferred Therapy:
  • Itraconazole 200 mg PO once daily (BI)
Discontinue Primary Prophylaxis:
  • If used, may discontinue if CD4 count ≥150 cells/mm3 for 6 months on ART (BIII)
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 or amphotericin B cholesteryl sulfate complex 3 mg/kg IV daily (AIII)
Duration: 
  • For at least 2 weeks or until clinically improved
Maintenance Therapy

Preferred Therapy:
  • Itraconazole 200 mg PO TID for 3 days, then BID for at least 12 months (AII), with dosage adjustment based on interactions with ARV (see Table 5) and itraconazole serum concentration 
Treating Less Severe Disseminated Disease

Induction and Maintenance Therapy

Preferred Therapy:
  • Itraconazole 200 mg PO TID for 3 days, then 200 mg PO BID for ≥12 months (AII), with dosage adjustment based on interactions with ARV and itraconazole serum concentration
Alternative Therapy:
Note: These recommendations are based on limited clinical data (for patients intolerant to itraconazole who are only moderately ill).
  • Posaconazole 400 mg PO BID (BIII)
  • Voriconazole 400 mg PO BID for 1 day, then 200 mg PO BID (BIII)
  • Fluconazole 800 mg PO 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 BID (TID for at least 12 months and until resolution of abnormal CSF findings) with dosage adjustment based on interactions with ARV and itraconazole serum concentration (AIII)
Long-Term Suppressive Therapy (Secondary Prophylaxis)

Indications:
  • For patients with severe disseminated or CNS infection after completion of at least 12 months of treatment (AIII), and 
  • In patients who relapsed despite appropriate initial therapy (BIII)
Preferred Therapy: 
  • Itraconazole 200 mg PO daily (AIII)
Alternative Therapy:
  • Fluconazole 400 mg PO daily (BIII)
Criteria for Discontinuing Long Term Suppressive Therapy (AI):
  • Received azole treatment for >1 year, and
  • Negative fungal blood cultures, and
  • Serum Histoplasma antigen <2 ng/mL, and
  • CD4 count >150 cells/mm3 for ≥6 months in response to ART
Indication for Restarting Secondary Prophylaxis:
  • CD4 count <150 cells/mm3 (BIII)
Other Considerations:
  • Itraconazole serum concentrations should be performed in all patients to ensure adequate absorption and to assess changes in hepatic metabolism due to drug interactions (AIII). Random serum concentrations (itraconazole + hydroxyitraconazole) should be >1 µg/mL.
  • Itraconazole oral solution is preferred over capsule because of improved absorption, but is less well tolerated. However, this formulation may not be necessary if itraconazole concentration is increased by concomitant use of a CYP3A4 inhibitor such as ritonavir-boosted PIs.
  • Acute pulmonary histoplasmosis in HIV-infected patients with CD4 count >300 cells/mm3 should be managed the same as for non-immunocompromised patients (AIII
  • All the triazole antifungals have the potential to interact with certain ARV agents and other anti-infective agents. These interactions are complex and can be bidirectional. Table 5 lists these interactions and recommends dosage adjustments where feasible.
Key to Acronyms: ART = antiretroviral therapy; ARV = antiretroviral; BID = twice daily; CD4 = CD4 T lymphocyte cell; CNS = central nervous system, CSF = cerebrospinal fluid; CYP3A4 = Cytochrome P450 3A4; IV = intravenous; PI = protease inhibitor; PO = orally; TID = three times daily

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