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

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.

Pneumocystis Pneumonia

Last Updated: March 28, 2019; Last Reviewed: June 26, 2019

Recommendations for Preventing and Treating Pneumocystis Pneumonia

Recommendations for Preventing and Treating PCP
Preventing First Episode of PCP (Primary Prophylaxis)

Indications for Initiating Primary Prophylaxis:
  • CD4 count <200 cells/mm3 (AI) or
  • CD4 percentage <14% of total lymphocyte count (BII) or
  • CD4 count >200 cells/mm3, but <250 cells/mm3 if ART initiation must be delayed and if CD4 count monitoring (e.g., every 3 months) is not possible (BII).
Note: Patients who are receiving pyrimethamine/sulfadiazine for treatment or suppression of toxoplasmosis do not require additional prophylaxis for PCP (AII).

Preferred Therapy:
  • TMP-SMX, 1 DS tablet PO dailya (AI) or
  • TMP-SMX, 1 SS tablet PO dailya (AI)
Alternative Therapy:
  • TMP-SMX 1 DS tablet PO three times weekly (BI) or
  • Dapsoneb,c 100 mg PO daily or dapsone 50 mg PO twice a day (BI) or
  • Dapsoneb 50 mg PO daily with (pyrimethamine 50 mg plus leucovorin 25 mg) PO weekly (BI) or
  • (Dapsoneb 200 mg plus pyrimethamine 75 mg plus leucovorin 25 mg) PO weekly (BI) or
  • Aerosolized pentamidinec 300 mg via Respigard II™ nebulizer every month (BI) or
  • Atovaquone 1500 mg PO daily with food (BI) or
  • (Atovaquone 1500 mg plus pyrimethamine 25 mg plus leucovorin 10 mg) PO daily with food (CIII).
Indication for Discontinuing Primary Prophylaxis:
  • CD4 count increased from <200 cells/mm3 to ≥200 cells/mm3 for ≥3 months in response to ART (AI)
  • Can consider when CD4 count is 100–200 cells/mm3 and HIV RNA remains below limit of detection of the assay used for ≥3 months to 6 months (BII)
Indication for Restarting Primary Prophylaxis:
  • CD4 count <100 cells/mm3 regardless of HIV RNA (AIII)
  • CD4 count 100–200 cells/mm3 and HIV RNA above detection limit of the assay used (AIII)

Treating PCP

Note: Patients who develop PCP despite TMP-SMX prophylaxis usually can be treated effectively with standard doses of TMP-SMX (BIII).

For Moderate to Severe PCP: Total Duration of Treatment is 21 Days (AII)

Preferred Therapy:

  • TMP-SMX: (TMP 15–20 mg and SMX 75–100 mg)/kg/day IV given every 6 or 8 hours (AI), may switch to PO formulations after clinical improvement (AI).
Alternative Therapy:
  • Pentamidine 4 mg/kg IV once daily infused over ≥60 minutes (AI); may reduce the dose to pentamidine 3 mg/kg IV once daily in the event of toxicities (BI), or
  • Primaquineb 30 mg (base) PO once daily plus (Clindamycin [IV 600 mg every 6 hours or 900 mg every 8 hours] or [PO 450 mg every 6 hours or 600 mg every 8 hours]) (AI).
Note: Adjunctive corticosteroids are indicated in moderate to severe cases of PCP (see indications and dosage recommendations below).

For Mild to Moderate PCP: Total Duration of Treatment is 21 Days (AII)
Preferred Therapy:
  • TMP-SMX: (TMP 15–20 mg/kg/day and SMX 75–100 mg/kg/day) PO (3 divided doses) (AI), or
  • TMP-SMX 2 DS tablets PO three times daily (AI)
Alternative Therapy:
  • Dapsoneb 100 mg PO daily plus TMP 15 mg/kg/day PO (3 divided doses) (BI) or
  • Primaquineb 30 mg (base) PO daily plus Clindamycin PO (450 mg every 6 hours or 600 mg every 8 hours) (BI) or
  • Atovaquone 750 mg PO twice daily with food (BI)
Adjunctive Corticosteroids
For Moderate to Severe PCP Based on the Following Criteria (AI):
  • PaO2 <70 mmHg at room air or
  • Alveolar-arterial DO2 gradient ≥35 mmHg

Dosing Schedule

:
  • Prednisone doses (beginning as soon as possible and within 72 hours of PCP therapy) (AI)
  • IV methylprednisolone can be given as 75% of prednisone dose.
Preventing Subsequent Episode of PCP (Secondary Prophylaxis)

Indications for Initiating Secondary Prophylaxis:
  • Prior PCP
Preferred Therapy:
  • TMP-SMX, 1 DS tablet PO dailya (AI) or
  • TMP-SMX, 1 SS tablet PO dailya (AI)
Alternative Therapy:
  • TMP-SMX 1 DS tablet PO three times weekly (BI) or
  • Dapsoneb,c 100 mg PO daily (BI) or
  • Dapsone 50 mg PO twice daily (BI) or
  • Dapsoneb 50 mg PO daily with (pyrimethamine 50 mg plus leucovorin 25 mg) PO weekly (BI) or
  • (Dapsoneb 200 mg plus pyrimethamine 75 mg plus leucovorin 25 mg) PO weekly (BI) or
  • Aerosolized pentamidinec 300 mg via Respigard II™ nebulizer every month (BI) or
  • Atovaquone 1500 mg PO daily with food (BI) or
  • (Atovaquone 1500 mg plus pyrimethamine 25 mg plus leucovorin 10 mg) PO daily with food (CIII)
Indications for Discontinuing Secondary Prophylaxis:
  • CD4 count increased from <200 cells/mm3 to >200 cells/mm3 for >3 months as a result of ART (BII) or
  • Can consider if CD4 count is 100–200 cells/mm3 and HIV RNA remains below limits of detection of assay used for ≥3 months to 6 months (BII)
  • For patients in whom PCP occurs at a CD4 count >200 cells/mm3 while not on ART, discontinuation of prophylaxis can be considered once HIV RNA levels are suppressed to below limits of detection of the assay used for ≥3 months to 6 months, although there are no data to support recommendations in this setting (CIII).
Note: If an episode of PCP occurs at a CD4 count >200 cells/mm3 while a patient is on ART, it would be prudent to continue PCP prophylaxis for life, regardless of how high the CD4 cell count rises as a consequence of ART (BIII).

Indications for Restarting Secondary Prophylaxis:
  • CD4 count <100 cells/mm3 regardless of HIV RNA (AIII)
  • CD4 count 100–200 cells/mm3 and HIV RNA above detection limit of the assay used (AIII).
Other Considerations/Comments:
  • For patients with non-life-threatening adverse reactions to TMP-SMX, the drug should be continued if clinically feasible.
  • If TMP-SMX is discontinued because of a mild adverse reaction, re-institution of therapy should be considered after the reaction has resolved (AII). The dose of TMP-SMX can be increased gradually (desensitization) (BI) or the drug can be given at a reduced dose or frequency (CIII).
  • Therapy should be permanently discontinued, with no rechallenge, in patients with suspected or confirmed Stevens-Johnson Syndrome or toxic epidermal necrolysis (AIII).

aTMP-SMX DS once daily also confers protection against toxoplasmosis and many respiratory bacterial infections; a lower dose also likely confers protection.
b Whenever possible, patients should be tested for G6PD deficiency before administration of dapsone or primaquine. An alternative agent should be used if the patient is found to have G6PD deficiency.
cAerosolized pentamidine or dapsone (without pyrimethamine) should not be used for PCP prophylaxis in patients who are seropositive for Toxoplasma gondii.

Key to Acronyms: ART = antiretroviral therapy; CD4 = CD4 T lymphocyte cell; DS = double strength; IV = intravenously; PCP = Pneumocystis pneumonia; PO = orally; SS = single strength; TMP = trimethoprim; TMP-SMX = trimethoprim-sulfamethoxazole

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