1. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents Histoplasmosis Slide Set
Prepared by the AETC National Resource Center based on recommendations from the CDC, National Institutes of Health, and HIV Medicine Association/Infectious Diseases Society of America

2. About This Presentation
These slides were developed using recommendations published in May The intended audience is clinicians involved in the care of patients with HIV.
Users are cautioned that, owing to the rapidly changing field of HIV care, this information could become out of date quickly. Finally, it is intended that these slides be used as prepared, without changes in either content or attribution. Users are asked to honor this intent.
-AETC National Resource Center
May 2013

3. Histoplasmosis: Epidemiology
Caused by Histoplasma capsulatum
Endemic in midwest United States, Puerto Rico, Latin America
Occurs in up to 5% of HIV-infected individuals in endemic areas
In nonendemic areas, usually seen in those who previously lived in endemic area
May 2013

4. Histoplasmosis: Epidemiology (2)
Acquired by inhalation
Risks include: working with surface soil, cleaning chicken coops contaminated with droppings; disturbing bird or bat droppings; exploring caves; cleaning, remodeling, or demolishing old buildings
May 2013

5. Histoplasmosis: Epidemiology (3)
Reactivation of latent infection may occur
Systemic illness more likely in patients with CD4 count <150 cells/µL
Pulmonary histoplasmosis may occur with CD4 count >300 cells/µL
Incidence has declined with use of potent ART
May 2013

6. Histoplasmosis: Clinical Manifestations
Disseminated disease: fever, fatigue, weight loss, hepatosplenomegaly
Cough, chest pain, dyspnea in 50%
Shock and multiorgan failure in 10%
Most common in patients with low CD4 count
Isolated pulmonary disease: usually occurs in patients with CD4 count >300 cells/µL
CNS, GI, and skin manifestations possible
CNS: fever, headache, seizures, focal neurological deficits, altered mental status
GI: fever, diarrhea, abdominal pain, weight loss
May 2013

7. Histoplasmosis: Clinical Manifestations (2)
Acute disseminated histoplasmosis, chest X ray (L) and CT scan (R)
Credit: Images courtesy AIDS Images Library (
May 2013

8. Histoplasmosis: Clinical Manifestations (3)
Skin lesions of histoplasmosis
Credit: Image courtesy AIDS Images Library (
May 2013

9. Histoplasmosis: Diagnosis
Detection of Histoplasma antigen in serum or urine
Sensitive for disseminated histoplasmosis and acute pulmonary infection
In disseminated disease, urine Ag test positive in up to 100%, serum Ag test positive in up to 92%
Ag detection in BAL fluid appears sensitive
Insensitive for chronic pulmonary infection
Biopsy with histopathologic examination shows characteristic budding yeast
May 2013

10. Histoplasmosis: Diagnosis (2)
Culture from blood, bone marrow, respiratory secretions, other involved sites (positive in >85%, but may take 2-4 weeks)
Serologic tests usually less useful in AIDS patients with disseminated disease, may be helpful in patients with higher CD4 counts and pulmonary disease
May 2013

11. Histoplasmosis: Diagnosis (3)
Diagnosis of meningitis may be difficult:
CSF cultures and fungal stains ≤50% sensitive
Antigen and antibody tests positive in up to 70% of cases
Consider presumptive diagnosis of Histoplasma meningitis if patient has disseminated histoplasmosis and CNS infection that is otherwise unexplained
CSF findings: lymphocytic pleocytosis, elevated protein, low glucose
May 2013

12. Histoplasmosis: Prevention
Preventing exposure:
In endemic areas, impossible to avoid exposure completely
Avoid higher-risk activities if CD4 <150 cells/µL
Primary prophylaxis
Itraconazole can reduce frequency of disease in patients with advanced HIV infection in highly endemic areas, but no survival benefit
Consider itraconazole 200 mg QD for patients with CD4 counts <150 cells/µL who are at high risk of infection (occupational exposure or hyperendemic area [>10 cases/100 patient-years])
Discontinuing primary prophylaxis
Discontinue when CD4 count ≥150 cells/µL for 6 months on effective ART
May 2013

13. Histoplasmosis: Treatment
Acute treatment consists of 2 phases: induction and maintenance
Total duration of therapy ≥12 months
May 2013

14. Histoplasmosis: Treatment (2)
Disseminated histoplasmosis
Moderate-severe disease
Induction (2 weeks or until clinically improved):
Preferred: liposomal amphotericin B 3 mg/kg IV QD
Alternative:
Amphotericin B lipid complex or cholesteryl sulfate complex 3 mg/kg IV QD
Maintenance: itraconazole 200 mg PO TID for 3 days, then BID* (liquid formulation preferred)
Duration of therapy: ≥12 months
* Adjust dosage based on interactions with ARVs and itraconazole serum concentration
May 2013

15. Histoplasmosis: Treatment (3)
Disseminated histoplasmosis
Less-severe disease
Induction and maintenance
Preferred: Itraconazole 200 mg PO TID for 3 days, then BID* (liquid formulation preferred)
Alternative (limited data):
Posaconazole 400 mg PO BID
Voriconazole 400 mg PO BID for 1 day, then 200 mg PO BID
Fluconazole 800 mg PO QD
Duration of therapy: ≥12 months
* Adjust dosage based on interactions with ARVs and itraconazole serum concentration
May 2013

16. Histoplasmosis: Treatment (4)
Meningitis
Preferred induction (4-6 weeks):
Liposomal amphotericin B 5 mg/kg IV QD
Preferred maintenance (≥12 months plus resolution of CSF abnormalities):
Itraconazole 200 mg PO BID or TID*
Acute pulmonary histoplasmosis in patients with CD4 count >300 cells/µL
Manage as in nonimmunocompromised
* Adjust dosage based on interactions with ARVs and itraconazole serum concentration
May 2013

17. Histoplasmosis: Treatment (5)
Other antifungals:
Echinocandins: not active against H capsulatum; should not be used
May 2013

18. Histoplasmosis: ART Initiation
Start ART as soon as possible after starting antifungal therapy
IRIS appears to be uncommon
Triazoles have complex, sometimes bidirectional interactions with certain ARVs; dosage adjustments may be needed
May 2013

19. Histoplasmosis: Monitoring and Adverse Events
Monitor serum or urine Histoplasma antigen: useful for determining response to therapy
Increase in level suggests relapse
Check serum itraconazole levels after 2 weeks of therapy or if potential drug interactions (absorption of itraconazole can be erratic)
IRIS is uncommon; ART should not be withheld because of concern for IRIS
May 2013

20. Histoplasmosis: Treatment Failure
Use liposomal amphotericin B for severely ill patients and those who do not respond to initial azole therapy
Consider posaconazole or voriconazole for moderately ill patients intolerant of itraconazole
Note: significant interactions between voriconazole and NNRTIs or ritonavir
May 2013

21. Histoplasmosis: Preventing Recurrence
Secondary prophylaxis:
Long-term suppressive therapy for patients with severe disseminated or CNS infection, after ≥12 months of treatment; and in those who relapse despite appropriate therapy
Preferred: itraconazole 200 mg PO
Alternative: fluconazole 400 mg PO QD (less effective than itraconazole)
Voriconazole or posaconazole: no data
May discontinue if: ≥12 months of itraconazole, and negative blood cultures, and Histoplasma serum Ag <2 ng/mL, and CD4 count ≥150 cells/µL on ART for ≥6 months on ART
Restart if CD4 count decreases to <150 cells/µL
May 2013

22. Histoplasmosis: Considerations in Pregnancy
Amphotericin B or its lipid formulations are preferred initial regimen
At delivery, evaluate neonate for renal dysfunction and hypokalemia
Azoles: avoid in 1st trimester--risk of teratogenicity
Voriconazole and posaconazole: teratogenic and embryotoxic in animals: avoid throughout pregnancy
May 2013

23. Websites to Access the Guidelines
May 2013

24. About This Slide Set
This presentation was prepared by Susa Coffey, MD, for the AETC National Resource Center in May 2013
See the AETC NRC website for the most current version of this presentation:
May 2013