This document discusses Pneumocystis jirovecii pneumonia (PJP) in patients with HIV/AIDS. PJP remains a leading opportunistic infection in this population. It is caused by an atypical fungus that exists within the alveoli. Clinical manifestations include gradual onset of fever, cough, dyspnea, and fatigue. Chest imaging shows diffuse bilateral infiltrates. Treatment involves TMP-SMX for 21 days, with steroids for moderate-severe disease. Complications like hyponatremia and hyperkalemia may occur and require treatment of underlying conditions like SIADH or adrenal insufficiency. Alternative regimens exist for those who cannot tolerate TMP-SMX. Secondary

1. PJP in HIV
by Tara Kerr

2. Pulm Infection Differential in HIV
• Tuberculosis
o Fever, cough, weight loss, night sweats, malaise
o CXR: vary from no evidence of dz to miliary
o Comparison: More severe constitutional symptoms
o Risk factors: endemic area, prison, household contact with active TB
• Nontuberculosis mycobacteria (MAC)
o CD4 <50
• Fungi (Histo)
o Fever, cough, diffuse interstitial infiltrates, elevated beta-D-glucan
o Comparison: adenopathy, hepatosplenomegaly, oral or other mucosal lesions
o Other fungal: crypto, cocci
• Toxoplasma (pneumonitis)
• fever, dyspnea, non-productive cough
• CXR with reticulonodular infiltrates

3. Pulm Infection Differential in HIV
• Cytomegalovirus (pneumonitis)
o CD4 <50
o Definitive dx: inclusion bodies on biopsy
• Influenza
o ACUTE onset of severe viral syndrome (fever, myalgia, headache), then progressive
dyspnea
o CXR: bilateral reticular or reticulonodular opacities with or without superimposed
consolidation
• Kaposi’s sarcoma
o Multi-focal nodular dz
o CD4 <100
o Up to 20% have no evidence of cutaneous dz
o Direct visualization of lesions on bronchoscopy is gold standard

4. PJP
• Incidence decreasing due to effective antiretroviral therapy (ART) and prophylaxis
• Remains a leading cause of opportunistic infection
• CD4 count <200
• Currently recognized as ATYPICAL FUNGUS
o Do not grown in fungal cultures
o Respond to some anti-parasitic agents, but not fungal agents
o Cell wall contains cholesterol, not ergosterol
• Transmission: primarily airborne
• Pathogen-host interaction: exists almost exclusively within alveoli
• Trophic form attaches to epithelial cells leading to enhanced proliferation

5. Clinical Manifestations
• Gradual onset
• Fever and/or chills
• Cough (non-productive)
• Dyspnea (progressing over days to weeks)
• Fatigue (climbing stairs, speaking on phone)
• Chest pain
• Weight loss
• 5-10% are asymptomatic

6. CXR
• Diffuse, bilateral, interstitial or alveolar infiltrates
• Less common:
o lobar or segmental infiltrates,
o cysts,
o nodules,
o pleural effusion
o pneumatoceles

7. CT
• Patchy or nodular ground glass opacities
o 100% sensitive, 89% specific

8. Definitive Dx
• Initiate empiric therapy in acutely ill patient if high suspicion
for PJP
o specimens may be difficult to obtain and quickly process
o tx doesn’t preclude definitive dx - cysts persist days to
weeks after start tx
• Visualization of cystic/trophic forms in respiratory secretions
• Important to obtain because tx requires prolonged course of
possibly toxic therapy
• Not uncommon to have alternative or co-occurring dz
• May forego definitive dx if clinical presentation and
radiographic findings highly consistent with PJP
o especially if beta-D-glucan markedly elevated

9. Initial Treatment
• Evaluate for respiratory rate, accessory muscle use, arterial oxygenation by pulse ox
• TMP-SMX is preferred (21 days)
o Mild to moderate disease, PO
o Severe dz, IV
• +/- steroids

10. Steroids
• Recommended for patients with moderate or severe disease or not improving in 4-8 days
• Pulse ox adequate for assessment (O2 sat <92% = give steroids)
• Decreases incidence of mortality and respiratory failure
• Regimen:
o Prednisone 40mg PO BID x 5 days
o Prednisone 40mg PO daily x 5 days
o Prednisone 20mg PO daily x 11 days
o Ok to sub IV methylpred at 75% of prednisone dose
• Monitor for development of opportunistic infections, especially candidiasis

11. So, you start treatment, things are improving, and then you get this lab:
Sodium 126
You think big buckets, but there’s one cause of hyponatremia that has some association with PJP

12. SIADH
• Euvolemic hyponatremia
• Dx of exclusion
• Pulmonary dz, particularly pneumonia, can lead to SIADH by unclear mechanism
• Fluid required to diluate IV TMP-SMX can also contribute

13. But wait, what if it isn’t PJP driving?
• Adrenal insufficiency also occurs in HIV and cause hyponatremia and hyperkalemia
o Cortisol deficiency leads to hyponatremia
 Tx: glucocorticoid (hydrocortisone)
o Aldosterone deficiency leads to hyperkalemia
 Tx: mineralocorticoid (fludrocortisone)
• Adrenal insufficiency in HIV often due to adrenalitis which can be caused by CMV, MAC, HIV,
Kaposi’s

14. Then, you get this lab:
Potassium: 5.8

15. Hyperkalemia
• Can be caused by trimethoprim or pentamidine and/or impaired renal function
• Mechanism is blockade of potassium secretion
• Dosing of trimethoprim in HIV pt is 5-10x higher than conventional tx
• Low renin release also occurs in HIV patients by unknown mechanism but mineralocorticoid
replacement may be needed (start with 0.05 to 0.1mg per day)

16. Adverse Reactions to TMP-SMX
• Common in PJP patients, ranging from mild to severe
• Continue TMP-SMX if adverse reaction is not life threatening
o GI intolerance, photosensitivity, mild rash, photosensitivity
• Stop immediately for the following:
o Persistent rash and/or fever for more than five days
o Absolute neutrophil count <500 cells/mm3
o Hypotension
o Intractable hyperkalemia
o Fever/flu-like symptoms, followed by conjunctival irritation, mucous membrane
involvement, painful skin, target lesions, blistering, desquamation

17. Alternative Regimens
• Tx with TMP-SMX even if patient prescribed TMP-SMX for prophylaxis
o non-adherence is most common cause of treatment failure
• Trimethoprim – dapsone
o Interaction between the two drugs may increase the levels of both drugs which may
increase risk of side effects
• Clindamycin – primaquine
o Check for G6PD deficiency as primaquine can cause hemolytic anemia
o Usually first choice in patients who fail to improve on IV TMP-SMX
• Atovaquone
o Alternative in mild dz
• Pentamidine
o Alternative in severe dz only due to potential for severe side effects including hypotension
and hypoglycemia

18. Secondary Prophylaxis
• After completing initial 21 days course, continue treatment with reduced dose
• Risk of recurrence w/o prophylaxis is 60-70% per year in patients not on ART
o Discontinue in patients on ART if:
o Undetectable viral load
o CD4 count >200 for at least three months