Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children

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 jirovecii Pneumonia

Last Updated: November 6, 2013; Last Reviewed: November 6, 2013

Panel's Recommendations for Pneumocystis jirovecii Pneumonia
Panel's Recommendations

Prevention of Primary Exposure

  • Some experts recommend that consideration be given to not placing a patient with Pneumocystis jirovecii pneumonia (PCP) in a hospital room with another patient and not placing an at-risk immunocompromised patient in a room with a patient who has a respiratory tract infection (BIII).

Chemoprophylaxis

  • Chemoprophylaxis is highly effective in preventing PCP. Prophylaxis is recommended for all HIV-infected children aged ≥6 years who have CD4 T lymphocyte (CD4) cell counts <200 cells/mm3 or CD4 percentage <15%, for children aged 1 to <6 years with CD4 counts <500 cells/mm3 or CD4 percentage <15%, and for all HIV-infected infants aged <12 months regardless of CD4 count or percentage (AII).
  • Infants with indeterminate HIV infection status should receive prophylaxis until they are determined to be HIV-uninfected or presumptively HIV-uninfected (AIII). HIV-infected infants should be administered prophylaxis until age 1 year, at which time they should be reassessed on the basis of the age-specific CD4 count or percentage thresholds mentioned above (AII).
  • Trimethoprim–sulfamethoxazole (TMP–SMX; cotrimoxazole), administered either on 3 consecutive days/week or daily, is the drug of choice for prophylaxis because of its high efficacy, relative safety, low cost, and broad antimicrobial spectrum (AI).
  • Other effective and safe prophylaxis regimens are available for patients unable to take TMP-SMX. A second choice would be either atovaquone (AI) or dapsone (BI*).
  • Aerosolized pentamidine is recommended for children who cannot take TMP-SMX, atovaquone, or dapsone and who are old enough to use nebulization with a Respirgard II® nebulizer (Marquest; Englewood, CO) (BI*).
  • Intravenous (IV) pentamidine is not recommended for prophylaxis unless no other options are available (BII).
  • Discontinuation of PCP prophylaxis should be considered for HIV-infected children when, after receiving combination antiretroviral therapy for ≥6 months, CD4 percentage is ≥15% or CD4 count is ≥200 cells/mm3 for patients aged ≥ 6 years (BII) and CD4 percentage is ≥15% or CD4 count is ≥500 cells/mm3 for patients aged 1 to <6 years (BII) for >3 consecutive months. Thereafter, CD4 percentage and CD4 count should be reevaluated at least every 3 months and prophylaxis reinstituted if the age-specific criteria for prophylaxis are reached (BIII).

Treatment

  • TMP-SMX, administered IV, is the recommended treatment for PCP (AI). As the acute pneumonitis subsides, children with mild-to-moderate disease who do not have malabsorption or diarrhea can be transitioned to oral treatment with the same total daily dose of TMP-SMX administered in 3 or 4 divided doses to complete a 21-day course (AII).
  • IV pentamidine isethionate once daily is recommended for patients who cannot tolerate TMP-SMX or who demonstrate clinical treatment failure after 5 to 7 days of TMP-SMX therapy (AI*).
  • Atovaquone is an alternative for treatment of mild-to-moderately severe PCP (BI*).
  • Dapsone/TMP is effective in treating mild-to-moderate PCP (BI*).
  • Clindamycin/primaquine has been used to treat mild-to-moderate PCP; data in children are unavailable (BIII).
  • A short course of corticosteroids is recommended in cases of moderate or severe PCP, starting within 72 hours of diagnosis (AI*).
  • Patients who have experienced an episode of PCP should continue on PCP prophylaxis after completion of treatment until CD4 counts exceed the threshold for initiating prophylaxis (AI).
  • Children who present with clinical signs and symptoms compatible with PCP after discontinuation of prophylaxis should be evaluated thoroughly despite normal or high CD4 counts or percentages (BI*).
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials in children with clinical outcomes and/or validated endpoints; I* = One or more randomized trials in adults with clinical outcomes and/or validated laboratory endpoints with accompanying data in children from one or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; II = One or more well-designed, nonrandomized trials or observational cohort studies in children† with long-term outcomes; II* = One or more well-designed, nonrandomized trials or observational studies in adults with long-term clinical outcomes with accompanying data in children from one or more similar nonrandomized trials or cohort studies with clinical outcome data; III = Expert opinion

Studies that include children or children/adolescents, but not studies limited to post-pubertal adolescents

Dosing Recommendations for Prevention and Treatment of Pneumocystis Pneumonia
Indication First Choice Alternative Comments/Special Issues
Primary Prophylaxis
  • TMP-SMX (Cotrimoxazole): TMP 2.5–5 mg/kg body weight/dose with SMX 12.5–25 mg/kg body weight/dose twice per day. Dosing based on TMP component.
  • The total daily dose should not exceed 320 mg TMP and 1600 mg SMX. Several dosing schemes have been used successfully—
    • Given 3 days per week on consecutive days or on alternate days
    • Given 2 days per week on consecutive days or on alternate days
    • Given every day (total daily dose of TMP 5–10 mg/kg body weight given as a single dose each day)
Dapsone
Children aged ≥1 months:
  • 2 mg/kg body weight (maximum 100 mg) by mouth once daily or 4 mg/kg body weight (maximum 200 mg) by mouth once weekly
Atovaquone
Children Aged 1–3 Months and >24 Months–12 Years:
  • 30-40 mg/kg body weight/dose by mouth once daily with food
Children Aged 4–24 Months:
  • 45 mg/kg body weight/dose by mouth once daily with food
Children Aged ≥13 Years:
  • 1500 mg (10 cc oral yellow suspension) per dose by mouth once daily
Aerosolized Pentamidine
Children Aged ≥5 Years:
  • 300 mg every month via Respirgard II™ nebulizer (manufactured by Marquest; Englewood, Colorado)
Primary Prophylaxis Indicated For:
  • All HIV-infected or HIV-indeterminate infants from aged 4–6 weeks to 12 months regardless of CD4 cell count/percentage
  • HIV-infected children aged 1 to <6 years with CD4 count <500 cells/mm3 or CD4 percentage <15%; HIV-infected children aged 6–12 years with CD4 count <200 cells/mm3 or CD4 percentage <15%
Criteria for Discontinuing Primary Prophylaxis:
Note: Do not discontinue in HIV-infected children aged <1 year
After ≥6 Months of cART:
  • Aged 1 to <6 years; CD4 percentage ≥15% or CD4 count is ≥500 cells/mm3 for >3 consecutive months, or
  • Aged ≥6 years, CD4 percentage ≥15% or CD4 count is ≥200 cells/mm3 for >3 consecutive months
Criteria for Restarting Primary Prophylaxis:
  • Aged 1 to < 6 years with CD4 percentage <15 or CD4 count <500 cells/mm3
  • Aged ≥6 years with CD4 percentage <15% or CD4 count <200 cells/mm3
Secondary Prophylaxis
Prior PCP
Same as for primary prophylaxis. Same as for primary prophylaxis. Secondary Prophylaxis Indicated For:
  • Children with prior episode of PCP
Criteria for Discontinuing Secondary Prophylaxis:
  • Same as for primary prophylaxis
Criteria for Restarting Secondary Prophylaxis:
  • Same as for primary prophylaxis 
Treatment TMP-SMX 3.75–5 mg/kg body weight/dose TMP (based on TMP component) every 6 hours IV or orally given for 21 days (followed by secondary prophylaxis dosing) If TMP-SMX-Intolerant or Clinical Treatment Failure After 5–7 Days of TMP-SMX Therapy
Pentamidine:
  • 4 mg/kg body weight/dose IV/IM once daily is the first choice alternative regimen. Note: Pentamidine can be changed to atovaquone after 7–10 days IV therapy.
Atovaquone
Daily Dosing: 
  • Children aged 1–3 months and >24 months–12 years: 30-40 mg/kg body weight/dose by mouth once daily with food
  • Children aged 4–24 months: 45 mg/kg body weight/dose by mouth once daily with food
Twice-Daily Dosing*:
  • Children aged ≥13 years: 750 mg/dose by mouth twice daily
After acute pneumonitis resolved in mild-moderate disease, IV TMP-SMX can be changed to oral. For oral administration, total daily dose of TMP-SMX can also be administered in 3 divided doses (every 8 hours).

Dapsone 2 mg/kg body weight by mouth once daily (maximum 100 mg/day) plus trimethoprim 5 mg/kg body weight by mouth every 8 hours has been used in adults but data in children are limited.

Primaquine base 0.3 mg/kg body weight by mouth once daily (maximum 30 mg/day) plus clindamycin 10 mg/kg body weight/dose IV or by mouth (maximum 600 mg given IV and 300–450 mg given orally) every 6 hours has been used in adults, but data in children are not available.
Indications for Corticosteroids:
  • PaO2 <70 mm Hg at room air or alveolar-arterial oxygen gradient >35 mm Hg
Prednisone Dose:
  • 1 mg/kg body weight/dose by mouth twice daily for 5 days, then 
  • 0.5–1 mg/kg body weight/dose by mouth twice daily for 5 days, then
  • 0.5 mg/kg body weight by mouth once daily for days 11 to 21. 
Alternative Corticosteroid Regimens Include: 
  • Adult dosage of prednisone: 40 mg/dose twice daily on days 1–5, 40 mg/dose once daily on days 6–10, 20 mg/dose once daily on days 11–21, and
  • Methylprednisolone IV 1 mg/kg/dose every 6 hours on days 1–7, 1 mg/kg/dose twice daily on days 8–9, 0.5 mg/kg/dose twice daily on days 10 and 11, and 1 mg/kg/dose once daily on days 12–16.
Chronic suppressive therapy (secondary prophylaxis) with TMP/SMX is recommended in children and adults following initial therapy (see Secondary Prophylaxis).
* Some experts use twice-daily dosing of atovaquone as alternative treatment for PCP in children aged <12 years:
  • Children aged 1–3 months and >24 months to 12 years: 15–20 mg/kg body weight/dose by mouth twice daily with food 
  • Children aged 4–24 months: 22.5 mg/kg body weight/dose by mouth twice daily with food.
Key to Acronyms: cART = combination antiretroviral therapy; CD4 = CD4 T lymphocyte cell; IM = intramuscular; IV = intravenous; PCP = Pneumocystis jirovecii pneumonia; TMP-SMX = trimethoprim-sulfamethoxazole

Note: Information included in these guidelines might not represent Food and Drug Administration (FDA) approval or approved labeling for products or indications. Specifically, the terms safe and effective might not be synonymous with the FDA-defined legal standards for product approval.

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