Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

high-risk for Pneumocystis pneumonia (PCP) infection

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primary prophylaxis

Indications for primary prophylaxis in HIV-positive adults or adolescents who do not have symptoms or signs of PCP include:[32] CD4 cell count <100 cells/microlitre; CD4 cell count between 100 and 200 cells/microlitre is plasma HIV RNA levels are above detection limits.

Prophylactic agent of choice is trimethoprim/sulfamethoxazole (TMP/SMX), in the absence of contraindications. Alternatives for patients, regardless of Toxoplasma gondii serostatus, include dapsone plus pyrimethamine plus folinic acid, or atovaquone. Alternatives for patients who are seronegative for Toxoplasma gondii include dapsone, aerosolised pentamidine, or intravenous pentamidine.[32]

PCP prophylaxis should be discontinued when patients have CD4 cell count ≥200 cells/microlitre for ≥3 consecutive months. Discontinuing PCP prophylaxis in patients on antiretroviral medication with suppressed viral loads and CD4 counts 100 to 200 cells/microlitre for ≥3 to 6 months may be considered. PCP prophylaxis should be restarted in patients with CD4 count <100 cells/microlitre regardless of the HIV viral load, and in patients with CD4 count ≥100 cells/microlitre to <200 cells/microlitre who do not have suppressed viral loads. PCP prophylaxis should be continued for life in patients who develop PCP despite CD4 count >200 cells/microlitre.[32]

All patients should be checked for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to starting dapsone, if possible.

Primary options

trimethoprim/sulfamethoxazole: 80/400 mg to 160/800 mg orally once daily

Secondary options

trimethoprim/sulfamethoxazole: 160/800 mg orally three times weekly

OR

dapsone: 100 mg orally once daily, or 50 mg orally twice daily

OR

dapsone: 50 mg orally once daily

and

pyrimethamine: 50 mg orally once weekly

and

calcium folinate: 25 mg orally once weekly

OR

dapsone: 200 mg orally once weekly

and

pyrimethamine: 75 mg orally once weekly

and

calcium folinate: 25 mg orally once weekly

OR

atovaquone: 1500 mg orally once daily

OR

pentamidine inhaled: 300 mg by nebuliser once monthly

OR

pentamidine: 300 mg intravenously every 28 days

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primary prophylaxis

Indications for primary prophylaxis in children include: HIV-positive infants aged 1-12 months regardless of CD4 cell count or percentage; HIV-positive children aged 1 to <6 years with CD4 count <500 cells/microlitre or CD4 percentage <15%; HIV-positive children aged ≥6 to 12 years with CD4 cell count <200 cells/microlitre or CD4 percentage <15%; HIV-indeterminate infants of HIV-positive mothers.[22]

Prophylactic agent of choice is trimethoprim/sulfamethoxazole (TMP/SMX), in the absence of contraindications. In patients who cannot tolerate TMP/SMX, other options include dapsone, atovaquone, or aerosolised pentamidine. Intravenous pentamidine may be considered in children aged >2 years when other options are not available.[22]

Children born to HIV-positive mothers should receive prophylaxis with TMP/SMX beginning at 4-6 weeks. Children who are HIV-positive at birth should be treated through their first year of life, at which time the need for ongoing PCP prophylaxis should be reassessed based on the age-specific CD4 count and percentage thresholds described previously. HIV-indeterminate infants of HIV-positive mothers should receive prophylaxis until they are determined to be HIV-uninfected.

Consideration can be given to discontinuation of PCP prophylaxis when, after receiving antiretroviral therapy for ≥6 months, CD4 percentage is ≥15% or CD4 cell count is ≥200 cells/microlitre for patients aged ≥6 years and CD4 percentage is ≥15% or CD4 cell count is ≥500 cell/microlitre for patients aged 1-6 years for >3 consecutive months. PCP prophylaxis should not be discontinued in HIV-infected infants aged <1 year.

After PCP prophylaxis has been discontinued, the CD4 percentage and CD4 count should be reassessed at least every 3 months and prophylaxis resumed based on the age-specific CD4 count and percentage thresholds described previously.

All patients should be checked for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to starting dapsone, if possible.

Primary options

trimethoprim/sulfamethoxazole: children ≥2 months of age: 5-10 mg/kg orally once daily; or 2.5 to 5 mg/kg twice daily given on 2 or 3 days per week either on consecutive days or on alternate days; maximum 320 mg/day

More

Secondary options

dapsone: children ≥1 month of age: 2 mg/kg orally once daily, maximum 100 mg/day; or 4 mg/kg orally once weekly, maximum 200 mg/dose

OR

atovaquone: children 1-3 months of age: 30-40 mg/kg orally once daily; children 4-24 months of age: 45 mg/kg orally once daily; children >24 months of age: 30-40 mg/kg orally once daily; maximum 1500 mg/day

OR

pentamidine inhaled: children ≥5 years of age: 300 mg by nebuliser once monthly

OR

pentamidine: children ≥2 years of age: 4 mg/kg intravenously once monthly

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primary prophylaxis

There are specific recommendations for PCP prophylaxis in patients who do not have HIV infection but are otherwise immunocompromised, for example during treatment for cancer.[47][98][101][108][109]​ Local guidelines should be consulted for information on suitable regimens.

In the 2018 American Society of Clinical Oncology and Infectious Diseases Society of America guidelines on antimicrobial prophylaxis in adults with cancer-related immunosuppression, indications for PCP prophylaxis include: patients receiving chemotherapy regimens associated with >3.5% risk of PCP infection (e.g., those with ≥20 mg/day prednisone [prednisolone] equivalents for ≥1 month or those taking purine analogues).​[47]

Trimethoprim/sulfamethoxazole (TMP/SMX) is the preferred first-line antibiotic, with aerosolised pentamidine, dapsone, or atovaquone if patients are intolerant to TMP/SMX.

All patients should be checked for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to starting dapsone, if possible.

Primary options

trimethoprim/sulfamethoxazole: 160/800 mg orally three times weekly

Secondary options

dapsone: 50 mg orally twice daily, or 100 mg once daily

OR

pentamidine inhaled: 300 mg by nebuliser once monthly

OR

atovaquone: 1500 mg orally once daily

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primary prophylaxis

There are specific recommendations for PCP prophylaxis in patients who do not have HIV infection but are otherwise immunocompromised, for example following solid-organ transplant.[49][98]​ Local guidelines should be consulted for information on suitable regimens.

The 2019 American Society of Transplantation guidelines recommend PCP prophylaxis for all solid-organ transplant recipients for at least 6-12 months and for programmes with incidence of PCP infection among recipients of at least 3% to 5%.[49]​ Lifelong prophylaxis may be indicated for small bowel and lung transplant recipients and patients with a history of previous PCP infection. Continuation or resumption of prophylaxis is generally indicated for patients treated with augmented immunosuppression for graft rejection, those with cytomegalovirus infection, patients receiving corticosteroids (e.g., >20 mg/day of prednisolone for ≥2 weeks) and during prolonged neutropenia or flares of autoimmune disease.

Prophylactic agent of choice is trimethoprim/sulfamethoxazole (TMP/SMX), in the absence of contraindications. In patients who cannot tolerate TMP/SMX, other options include dapsone, atovaquone, aerosolised pentamidine, or clindamycin plus pyrimethamine (this combination has not been studied adequately in children and is recommended for adults only).[49]

All patients should be checked for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to starting dapsone, if possible.

Primary options

trimethoprim/sulfamethoxazole: children ≥2 months of age: 5-10 mg/kg orally once daily, or 5-10 mg/kg/day orally given in 2 divided doses on 2 or 3 days per week, maximum 320 mg/day; adolescents and adults: 160 mg orally once daily or three times weekly, or 80 mg orally once daily

More

Secondary options

dapsone: children ≥1 month of age: 2 mg/kg orally once daily (maximum 100 mg/day), or 4 mg/kg once weekly (maximum 200 mg/dose); adolescents and adults: 50-100 mg orally once daily

OR

atovaquone: children 1-3 months of age: 30-40 mg/kg orally once daily, maximum 1500 mg/day; children 4-24 months of age: 45 mg/kg orally once daily, maximum 1500 mg/day; children >24 months of age: 30-40 mg/kg orally once daily, maximum 1500 mg/day; adolescents and adults: 1500 mg orally once daily

OR

pentamidine inhaled: children, adolescents, and adults: 300 mg by nebuliser every 3-4 weeks

Tertiary options

clindamycin: adults: 300 mg orally once daily or three times weekly

and

pyrimethamine: adults: 15 mg orally once daily or three times weekly

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primary prophylaxis

There are specific recommendations for PCP prophylaxis in patients who do not have HIV infection but are otherwise immunocompromised, for example following haematopoietic cell transplant.[48][101][108][109]​​​​ Local guidelines should be consulted for information on suitable regimens.

The 2009 multi-society-sponsored North American and European guidelines for preventing infectious complications following haematopoietic cell transplantation recommend PCP prophylaxis for all allogeneic haematopoietic cell transplant recipients and for autologous haematopoietic cell transplant recipients with significant immunosuppression (i.e., patients with underlying haematological malignancies, those receiving intensive conditioning regimens or graft manipulation, or those who have recently received purine analogues or high-dose corticosteroids).[48]​ For allogeneic haematopoietic cell transplant recipients, PCP prophylaxis is recommended from engraftment until at least 6 months after transplantation. Initiating PCP prophylaxis for 1-2 weeks prior to transplantation may be considered on the basis of underlying disease, prior chemotherapy, and pre-transplant conditioning regimens. For autologous haematopoietic cell transplant recipients with significant immunosuppression, PCP prophylaxis is recommended from engraftment until 3-6 months after transplantation. PCP prophylaxis should be extended for longer than 6 months in allogeneic or autologous haematopoietic cell transplant recipients who continue to receive immunosuppressive drugs (e.g., prednisolone or ciclosporin) or have chronic graft-versus-host disease.[48]

Prophylactic agent of choice is trimethoprim/sulfamethoxazole (TMP/SMX), in the absence of contraindications. In patients who cannot tolerate TMP/SMX, alternative options include atovaquone, dapsone, aerosolised pentamidine, or intravenous pentamidine.[48]

All patients should be checked for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to starting dapsone, if possible.

Primary options

trimethoprim/sulfamethoxazole: children ≥2 months of age: 150 mg/square metre of body surface area/day orally (multiple regimens exist); adolescents and adults: 80-160 mg orally once daily, or 160 mg three times weekly

More

Secondary options

dapsone: children ≥1 month of age: 2 mg/kg orally once daily, maximum 100 mg/day; adolescents and adults: 50 mg orally twice daily, or 100 mg once daily

OR

atovaquone: children: 15 mg/kg orally twice daily, or 30 mg/kg once daily; adolescents and adults: 750 mg orally twice daily, or 1500 mg once daily

OR

pentamidine inhaled: children ≤5 years of age: 9 mg/kg by nebuliser once monthly; children >5 years of age: 300 mg by nebuliser once monthly; adolescents and adults: 300 mg by nebuliser every 3-4 weeks

OR

pentamidine: children: 4 mg/kg intravenously every 2-4 weeks

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ACUTE

adults or adolescents: HIV-positive

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pharmacotherapy

Defined as having both a room air pO₂ ≥70 mmHg and an A-a gradient ≤35 mmHg.

Treatment of choice is trimethoprim/sulfamethoxazole (TMP/SMX).[32]

Alternative treatments should only be used if patients are intolerant to TMP/SMX and cannot be managed supportively, or if there is evidence of treatment failure. Because patient symptoms and signs often worsen within the first 3-5 days of treatment, treatment failure is considered if the patient has worsening clinical status after at least 4-8 days of therapy.[32] Alternative treatments include dapsone plus trimethoprim, clindamycin plus primaquine, or atovaquone.

All patients should be checked for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to starting primaquine or dapsone, if possible.

Duration of therapy is 21 days.

Primary options

trimethoprim/sulfamethoxazole: 15-20 mg/kg/day orally given in 3 divided doses, or 320 mg orally three times daily

More

Secondary options

dapsone: 100 mg orally once daily

and

trimethoprim: 15 mg/kg/day orally given in 3 divided doses

OR

clindamycin: 450 mg orally four times daily, or 600 mg three times daily

and

primaquine: 30 mg orally once daily

More

OR

atovaquone: 750 mg orally twice daily

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pharmacotherapy ± mechanical ventilation

Defined by either a room air pO₂ <70 mmHg or an A-a gradient >35 mmHg.

Patients with respiratory compromise should be admitted to hospital, possibly to the intensive care unit, and may require mechanical ventilation.

Treatment of choice is intravenous trimethoprim/sulfamethoxazole (TMP/SMX).[32] Alternative treatment regimens include either clindamycin plus primaquine, or intravenous pentamidine. Clindamycin plus primaquine may be more effective and less toxic than intravenous pentamidine.[100] Alternative treatments should only be used if patients are intolerant to TMP/SMX and cannot be managed supportively, or if there is evidence of treatment failure. As patients often worsen within the first 3-5 days of treatment, treatment failure is considered if the patient has worsening clinical status after at least 4-8 days of therapy.[32]

All patients should be checked for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to starting primaquine, if possible.

Duration of therapy is 21 days.

Primary options

trimethoprim/sulfamethoxazole: 15-20 mg/kg/day intravenously given in divided doses every 6-8 hours

More

Secondary options

pentamidine: 4 mg/kg intravenously every 24 hours

More

OR

clindamycin: 600 mg intravenously every 6 hours, or 900 mg every 8 hours; 450 mg orally four times daily, or 600 mg three times daily

and

primaquine: 30 mg orally once daily

More
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Plus – 

corticosteroid

Treatment recommended for ALL patients in selected patient group

All patients should be given a corticosteroid, started as early as possible, preferably within the first 72 hours.[99]

Primary options

prednisolone: 40 mg orally twice daily for 5 days, followed by 40 mg once daily for 5 days, followed by 20 mg once daily for 11 days

OR

methylprednisolone: 30 mg intravenously twice daily for 5 days, followed by 30 mg once daily for 5 days, then 15 mg once daily until patient can be given oral prednisone

children: HIV-positive or at risk for HIV

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pharmacotherapy

Defined as having both a room air pO₂ ≥70 mmHg and an A-a gradient ≤35 mmHg.

Treatment of choice is trimethoprim/sulfamethoxazole (TMP/SMX).[22]

Alternative treatments should be given if the child does not tolerate TMP/SMX or if there is clinical treatment failure after 5-7 days.[22] Alternative treatment regimens include intravenous pentamidine, atovaquone, dapsone plus trimethoprim, or primaquine plus clindamycin.[22]

All patients should be checked for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to starting primaquine or dapsone, if possible.

Duration of therapy is 21 days.

Primary options

trimethoprim/sulfamethoxazole: children ≥2 months of age: 15-20 mg/kg/day intravenously given in divided doses every 6 hours

More

Secondary options

pentamidine: 4 mg/kg intravenously every 24 hours

More

OR

atovaquone: children 1-3 months of age: 30-40 mg/kg orally once daily; children 4-24 months of age: 45 mg/kg orally once daily; children >24 months of age: 30-40 mg/kg orally once daily; maximum 1500 mg/day

OR

dapsone: 2 mg/kg orally once daily, maximum 100 mg/day

and

trimethoprim: 15 mg/kg/day orally given in 3 divided doses

OR

clindamycin: 10 mg/kg intravenously/orally every 6 hours, maximum 600 mg/dose (intravenously) or 300-450 mg/dose (orally)

and

primaquine: 0.3 mg/kg orally once daily, maximum 30 mg/day

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pharmacotherapy ± mechanical ventilation

Defined by either a room air pO₂ <70 mmHg or an A-a gradient >35 mmHg.

Children with respiratory compromise should be admitted to the hospital, possibly to the intensive care unit, and given ventilation.

Treatment of choice is trimethoprim/sulfamethoxazole (TMP/SMX).[22]

Pentamidine may be used as an alternative if the child does not tolerate TMP/SMX or if there is clinical treatment failure after 5-7 days of TMP/SMX therapy.[22]

All patients should be checked for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to starting primaquine, if possible.

Duration of therapy is 21 days.

Primary options

trimethoprim/sulfamethoxazole: children ≥2 months of age: 15-20 mg/kg/day intravenously given in divided doses every 6 hours

More

Secondary options

pentamidine: 4 mg/kg intravenously every 24 hours

More
Back
Plus – 

corticosteroid

Treatment recommended for ALL patients in selected patient group

All patients should be given a corticosteroid, started as early as possible, preferably within the first 72 hours.[22] [ Cochrane Clinical Answers logo ]

Primary options

prednisolone: 1 mg/kg orally twice daily for 5 days, then 0.5 to 1 mg/kg orally twice daily for 5 days, then 0.5 mg/kg orally once daily for 11 days

Secondary options

prednisolone: 40 mg orally twice daily for 5 days, then 40 mg once daily for 5 days, then 20 mg/kg once daily for 11 days

OR

methylprednisolone: 1 mg/kg intravenously every 6 hours on days 1-7, followed by 1 mg/kg every 12 hours on days 8-9, then 0.5 mg/kg every 12 hours on days 10-11, then 1 mg/kg every 24 hours on days 12-16

immunocompromised adults or adolescents: HIV-negative and not solid-organ transplant recipients

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pharmacotherapy ± mechanical ventilation

There are specific recommendations for pharmacological treatment of PCP in patients who do not have HIV infection but are otherwise immunocompromised, for example following transplantation or malignancy.[49][98][101]​ Local guidelines should be consulted for information on suitable regimens.

Patients with respiratory compromise should be admitted to the hospital, possibly to the intensive care unit, and may require mechanical ventilation.

The 2010 American Thoracic Society guidelines recommend trimethoprim/sulfamethoxazole (TMP/SMX) as the preferred treatment for PCP in immunocompromised adults. The alternative treatment options include intravenous pentamidine, atovaquone, or clindamycin plus primaquine.[98] Alternative regimens should only be used if the patient does not tolerate TMP/SMX or if there is clinical treatment failure after 4-8 days of TMP/SMX therapy.

All patients should be checked for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to starting primaquine or dapsone, if possible.

Duration of therapy is 14-21 days.

Primary options

trimethoprim/sulfamethoxazole: 15-20 mg/kg/day intravenously/orally given in divided doses every 6-8 hours

More

Secondary options

pentamidine: 4 mg/kg intravenously every 24 hours

More

OR

atovaquone: 750 mg orally twice daily

OR

clindamycin: 600 mg intravenously every 6 hours, or 900 mg every 8 hours; 450 mg orally four times daily, or 600 mg three times daily

and

primaquine: 30 mg orally once daily

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Consider – 

corticosteroid

Additional treatment recommended for SOME patients in selected patient group

The use of adjuvant corticosteroids in HIV-negative-associated severe PCP has been controversial, with meta-analyses of observational studies reporting conflicting findings regarding mortality, including in hypoxaemic patients.[61][103][104][105][106][107]

Primary options

prednisolone: 40 mg orally twice daily for 5 days, followed by 40 mg once daily for 5 days, followed by 20 mg once daily for 11 days

OR

methylprednisolone: 30 mg intravenously twice daily for 5 days, followed by 30 mg once daily for 5 days, then 15 mg once daily until patient can be given oral prednisone

immunocompromised adults or adolescents or children: HIV-negative and solid-organ transplant recipients

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pharmacotherapy ± mechanical ventilation

There are specific recommendations for pharmacological treatment of PCP in patients who do not have HIV infection but are otherwise immunocompromised, for example following transplantation.[49][98]​ Local guidelines should be consulted for information on suitable regimens.

Patients with respiratory compromise should be admitted to the hospital, possibly to the intensive care unit, and may require mechanical ventilation.

The 2019 American Society of Transplantation guidelines also recommend trimethoprim/sulfamethoxazole (TMP/SMX) as the preferred PCP treatment in children and adult solid-organ transplant recipients.[49]​ Oral dosing may be considered in mild infections. In severe infections, intravenous pentamidine is the preferred second-line agent after TMP/SMX; however, it should be avoided in pancreas recipients due to the potential for islet cell necrosis. Other options for mild-moderate PCP include atovaquone or clindamycin plus primaquine, and options for mild-moderate or moderate-severe PCP include dapsone plus trimethoprim, or pyrimethamine plus sulfadiazine; however, these combinations regimens have not been studied adequately in children.[49]

All patients should be checked for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to starting primaquine or dapsone, if possible.

Duration of therapy is 14-21 days.

Primary options

trimethoprim/sulfamethoxazole: children ≥2 months of age: 15-20 mg/kg/day intravenously/orally given in divided doses every 6-8 hours; adolescents and adults: 15-20 mg/kg/day intravenously/orally given in divided doses every 6-8 hours, or 320 mg orally three times daily

More

Secondary options

pentamidine: children, adolescents, and adults: 4 mg/kg intravenously every 24 hours

More

Tertiary options

atovaquone: children 1-3 months of age: 30-40 mg/kg/day orally given in 1-2 divided doses, maximum 1500 mg/day; children 4-24 months of age: 45 mg/kg/day orally given in 1-2 divided doses, maximum 1500 mg/day; children >24 months of age: 30-40 mg/kg/day orally given in 1-2 divided doses, maximum 1500 mg/day; adolescents and adults: 750-1500 mg orally twice daily

OR

dapsone: 100 mg orally once daily

and

trimethoprim: 15 mg/kg/day orally given in 3 divided doses

OR

clindamycin: 600-900 mg intravenously/orally every 6-8 hours

and

primaquine: 15-30 mg orally once daily

OR

pyrimethamine: consult specialist for guidance on dose

and

sulfadiazine: consult specialist for guidance on dose

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Consider – 

corticosteroid

Additional treatment recommended for SOME patients in selected patient group

The use of adjuvant corticosteroids in HIV-negative-associated severe PCP has been controversial, with meta-analyses of observational studies reporting conflicting findings regarding mortality, including in hypoxaemic patients.[61][103][104][105][106][107]

Primary options

prednisolone: children: 1 mg/kg orally twice daily for 5 days, followed by 0.5 mg/kg twice daily for 5 days, then 0.5 mg/kg once daily for 10 days; adults: 40-60 mg orally two to three times daily for 5-7 days, then taper over 1-2 weeks

ONGOING

completed successful treatment of PCP infection

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secondary prophylaxis

Patients who have had PCP infection, who have been treated and are without symptoms, receive secondary prophylaxis, which conforms to the same schedule as primary prophylaxis for each patient group.

Secondary prophylaxis is recommended for HIV-positive patients who have had PCP and should be started after completion of PCP treatment and continued until immune reconstitution occurs with antiretroviral therapy.[22][32]

Secondary prophylaxis can be discontinued for most patients using the same criteria as for discontinuing primary prophylaxis. PCP prophylaxis should not be discontinued in HIV-infected infants aged <1 year. Prophylaxis should be continued for life in patients who develop PCP despite CD4 count >200 cells/microlitre.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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