Pneumocystis jirovecii Pneumonia (PcP)

Primary Prophylaxis

Start: if CD4 count < 200 cells/μL, CD4 percentage < 14%, oral thrush or relevant concomitant immunosuppression, see Primary Prophylaxis of OIs

Stop: if CD4 count > 100 cells/μL and HIV-VL undetectable over 3 months

	Drug / Dose	Comments
Negative or positive serology for toxoplasmosis	TMP-SMX 80/400 mg qd po or 160/800 mg qd po or 160/800 mg x 3/week po	In case of non-severe TMP-SMX allergy and if other therapeutic options are not available/not clinically appropriated, desensitization can be attempted *
Negative serology for toxoplasmosis	pentamidine 300 mg in 6 mL sterile water x 1 inhalation/month	Does not prevent the rare extrapulmonary manifestations of P. jirovecii
Negative serology for toxoplasmosis	dapsone 100 mg qd po	Check for G6PD-deficiency
Negative serology for toxoplasmosis	atovaquone suspension 1500 mg qd po (with food)
Positive serology for toxoplasmosis	dapsone 200 mg/week po + pyrimethamine 75 mg/week po + folinic acid 25-30 mg/week po	Check for G6PD-deficiency
Positive serology for toxoplasmosis	atovaquone suspension 1500 mg qd po (with food) +/- pyrimethamine 75 mg/week po + folinic acid 25-30 mg /week po

* for protocols see: J. Allerg. Clin. Immunol 1994; 93:1001-1005; J Infect Dis 2001 Oct 15;184(8):992-7

Diagnosis and treatment

Diagnosis:
Definitive diagnosis: Cough and dyspnea on exertion AND microorganism identification by cytology / histopathology of induced sputum (sensitivity up to 80%), broncho-alveolar lavage (sensitivity > 95%) or bronchoscopic tissue biopsy (sensitivity > 95%)

Presumptive diagnosis: CD4 count < 200 cells/μL AND dyspnea / desaturation on exertion and cough AND radiology compatible with PcP AND no evidence for bacterial pneumonia AND response to PcP treatment. SARS-CoV-2 pneumonia can resemble PcP and should therefore be included in the differential diagnoses.

Notes on treatment:
treat at least 21 days, then secondary prophylaxis until CD4 count > 100 cells/μL and HIV-VL undetectable over 3 months. See also Anti-infective/ART interaction table for treatment optimization

	Drug / Dose	Comments
Preferred therapy	TMP-SMX 5 mg/kg tid TMP iv/po + 25 mg/kg tid SMX iv/po	Monitor myelotoxicity (mainly neutropenia), kidney function and electrolytes (mainly high potassium)
+ prednisone 40 mg bid po 5 days 40 mg qd po 5 days 20 mg qd po 10 days if PaO₂ < 10 kPa or < 70 mmHg or alveolar/arterial O₂ gradient > 35 mmHg. Start prednisone preferentially 15-30 min before TMP/SMX	Benefit of corticosteroids if started within 72 hours after start of treatment
Alternative therapy for moderate to severe PcP	primaquine 30 mg (base) qd po	Check for G6PD deficiency
+ clindamycin 600-900 mg tid iv/po
OR pentamidine 4 mg/kg qd iv (infused over 60 min.)
For each regimen: + prednisone 40 mg bid po 5 days 40 mg qd po 5 days 20 mg qd po 10 days if PaO₂ < 10 kPa or < 70 mmHg or alveolar/arterial O₂ gradient > 35 mmHg. Start prednisone preferentially 15-30 min before TMP/SMX	Benefit of corticosteroids if started within 72 hours after start of treatment Some studies support the addition of caspofungin or other echinocandins to standard treatment in persons with moderate-severe PcP (can be considered, but not mandatory)
Alternative therapy for mild to moderate PcP	primaquine 30 mg (base) qd po	Check for G6PD deficiency
+ clindamycin 600-900 mg tid po
OR atovaquone suspension 750 mg bid po (with food)
OR dapsone 100 mg qd po	Check for G6PD deficiency. In case of rash: reduce dose of TMP (50%), antihistamines
+ trimethoprim 5 mg/kg tid po

Drug / Dose

Comments

Preferred therapy

TMP-SMX
5 mg/kg tid TMP iv/po
+ 25 mg/kg tid SMX iv/po

Monitor myelotoxicity (mainly neutropenia), kidney function and electrolytes (mainly high potassium)

+ prednisone
40 mg bid po 5 days
40 mg qd po 5 days
20 mg qd po 10 days
if PaO₂ < 10 kPa or < 70 mmHg or alveolar/arterial O₂ gradient > 35 mmHg. Start prednisone preferentially 15-30 min before TMP/SMX

Benefit of corticosteroids if started within 72 hours after start of treatment

Alternative therapy for moderate to severe PcP

primaquine
30 mg (base) qd po

Check for G6PD deficiency

+ clindamycin
600-900 mg tid iv/po

OR
pentamidine
4 mg/kg qd iv (infused over 60 min.)

For each regimen:
+ prednisone
40 mg bid po 5 days
40 mg qd po 5 days
20 mg qd po 10 days
if PaO₂ < 10 kPa or < 70 mmHg or alveolar/arterial O₂ gradient > 35 mmHg. Start prednisone preferentially 15-30 min before TMP/SMX

Benefit of corticosteroids if started within 72 hours after start of treatment

Some studies support the addition of caspofungin or other echinocandins to standard treatment in persons with moderate-severe PcP (can be considered, but not mandatory)

Alternative therapy for mild to moderate PcP

primaquine
30 mg (base) qd po

Check for G6PD deficiency

+ clindamycin
600-900 mg tid po

OR
atovaquone suspension
750 mg bid po (with food)

OR
dapsone
100 mg qd po

Check for G6PD deficiency.

In case of rash: reduce dose of TMP (50%), antihistamines

+ trimethoprim
5 mg/kg tid po

Secondary Prophylaxis / Maintenance Therapy

Stop: if CD4 count > 100 cells/μL and HIV-VL undetectable over 3 months

	Drug / Dose	Comments
Negative or positive serology for toxoplasmosis	TMP-SMX 400/80 mg qd po or 160/800 mg x 3/week po
Negative serology for toxoplasmosis	pentamidine 300 mg in 6 mL sterile water x 1 inhalation/month	Not to use in the rare case of extrapulmonary manifestations of P. jirovecii
Negative serology for toxoplasmosis	dapsone 100 mg qd po	Check for G6PD-deficiency
Negative serology for toxoplasmosis	atovaquone suspension 1500 mg qd po (with food)
Positive serology for toxoplasmosis	dapsone 200 mg/week po + pyrimethamine 75 mg/week po + folinic acid 25-30 mg/week po	Check for G6PD-deficiency
Positive serology for toxoplasmosis	atovaquone suspension 1500 mg qd po (with food) +/- pyrimethamine 75 mg/week po + folinic acid 25-30 mg/week po