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.

Mycobacterium avium Complex Disease

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

Panel's Recommendations for Mycobacterium avium Complex Disease
Panel's Recommendations
  • Routine screening of respiratory or gastrointestinal specimens for Mycobacterium avium complex (MAC) microorganisms is not recommended (BIII), but a blood culture for MAC should be obtained to rule out disseminated disease before initiating prophylaxis (AIII).
  • Prophylaxis with either clarithromycin or azithromycin should be offered to HIV-infected children who have advanced immunosuppression (AII).
    • Children aged <1 year: <750 cells/mm3
    • Children aged 1 to <2 years: <500 cells/mm3
    • Children aged 2 to <6 years: <75 cells/mm3
    • Children aged ≥6 years: <50 cells/mm3

Discontinuing Primary Prophylaxis:

  • Primary prophylaxis can be discontinued in HIV-infected children aged ≥2 years receiving stable combination antiretroviral therapy (cART) for ≥6 months and experiencing sustained (>3 months) CD4 T lymphocyte (CD4) cell count recovery well above the age-specific target for initiation of prophylaxis (i.e., as in adults, >100 cells/mm3 for children aged ≥6 years (AI); and >200 cells/mm3 for children aged 2 to <6 years) (BII*).

Treating Disease:

  • Testing of MAC isolates for susceptibility to clarithromycin or azithromycin is recommended (BIII). Combination therapy with a minimum of two drugs (e.g., clarithromycin or azithromycin plus ethambutol) is recommended to prevent or delay the emergence of resistance (AI*). Some experts use clarithromycin as the preferred first agent (AI*), reserving azithromycin for patients with substantial intolerance to clarithromycin or when drug interactions with clarithromycin are a concern (AII*).
  • Use of rifabutin as a third drug added to the macrolide/ethambutol regimen is controversial. Some experts would add rifabutin as a third drug to the clarithromycin/ethambutol regimen, particularly in the absence of cART and in the presence of high mycobacterial counts (CIII); however, drug interactions should be checked carefully, and more intensive toxicity monitoring may be warranted with such combination therapy (AIII). Other experts recommend against using this third agent in children because of rifabutin’s increased cytochrome P450 activity, which leads to increased clearance of other drugs such as protease inhibitors and non-nucleoside reverse transcriptase inhibitors, and the potential for increased toxicity associated with concomitant administration of drugs (CIII).
  • Treatment failure is defined as the absence of clinical response and the persistence of mycobacteremia after 8 to 12 weeks of treatment. Repeat susceptibility testing of MAC isolates is recommended in this situation, and a new multidrug regimen of two or more drugs not previously used and to which the isolate is susceptible should be administered (AIII). Drugs that should be considered for this scenario include rifabutin, amikacin, and a quinolone.

Secondary Prophylaxis:

  • Children with a history of disseminated MAC and continued immunosuppression should receive lifelong prophylaxis to prevent recurrence (AII*). Secondary prophylaxis typically consists of continued multidrug therapy used in treatment of disease.
  • Some experts recommend discontinuation of therapy in HIV-infected children who meet all of the following criteria:
    • Aged ≥2 years and have completed ≥12 months of treatment for MAC; 
    • Remain asymptomatic for MAC; 
    • Receiving stable cART (i.e., cART not requiring change for virologic or immunologic failure); 
    • Have sustained (≥6 months) CD4 count recovery well above the age-specific target for initiation of primary prophylaxis (i.e., as in adults, >100 cells/mm3 for children aged ≥ 6 years (AII*) and >200 cells/mm3 for children aged 2 to <6 years) (CIII).
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 Mycobacterium avium Complex (MAC)
Preventive Regimen
Indication First Choice Alternative Comments/Special Issues
Primary Prophylaxis
  • Clarithromycin 7.5 mg/kg body weight (maximum 500 mg) by mouth orally twice daily, or
  • Azithromycin 20 mg/kg body weight (maximum 1200 mg) orally once weekly
  • Azithromycin 5 mg/kg body weight (maximum 250 mg) orally once daily
  • Children aged >5 years: rifabutin 300 mg orally once daily with food
Primary Prophylaxis Indicated for Children: 
  • Aged <1 year with CD4 count <750 cells/mm3;
  • Aged 1 to <2 years with CD4 count <500 cells/mm3;
  • Aged 2 to <6 years with CD4 count <75 cells/mm3;
  • Aged ≥6 years with CD4 count <50 cells/mm3

Criteria for Discontinuing Primary Prophylaxis:

  • Do not discontinue in children age <2 years.
  • After ≥6 months of cART and: 
  • Aged 2 to <6 years with CD4 count >200 cells/mm3 for >3 consecutive months
  • Aged ≥6 years with CD4 count >100 cells/mm3 for >3 consecutive months
Criteria for Restarting Primary Prophylaxis:
  • Aged 2 to <6 years with CD4 count <200 cells/mm3
  • Aged ≥6 years with CD4 count <100 cells/mm3
Secondary Prophylaxis
(Chronic Suppressive Therapy)
  • Clarithromycin 7.5 mg/kg body weight (maximum 500 mg) orally twice daily, plus 
  • Ethambutol 15–25 mg/kg body weight (maximum 2.5 g) orally once daily, with or without food
  • Children aged >5 years  who received rifabutin as part of initial treatment: Rifabutin 5 mg/kg body weight (maximum 300 mg) orally once daily with food
  • Azithromycin 5 mg/kg body weight (maximum 250 mg) orally once daily, plus 
  • Ethambutol 15–25 mg/kg body weight (max 2.5 g) orally once daily, with or without food
  • Children aged >5 years  who received rifabutin as part of initial treatment: Rifabutin 5 mg/kg body weight (maximum 300 mg) orally once daily with food.
Secondary Prophylaxis Indicated:
  • Prior disease 
Criteria for Discontinuing Secondary Prophylaxis
Fulfillment of All of the Following Criteria: 
  • Completed ≥6 months of cART 
  • Completed ≥12 months MAC therapy
  • Asymptomatic for signs and symptoms of MAC 
  • Aged 2 to <6 years with CD4 count >200 cells/mm3 for ≥6 consecutive months
  • Aged ≥6 years with CD4 count >100 cells/mm3 for ≥6 consecutive months
Criteria for Restarting Secondary Prophylaxis:
  • Aged 2 to <6 years with CD4 count <200 cells/mm3
  • Aged ≥6 years with CD4 count <100 cells/mm3
Treatment Initial Treatment (≥2 Drugs): 
  • Clarithromycin 7.5–15 mg/kg body weight (maximum 500 mg/dose) orally twice daily plus ethambutol 15–25 mg/kg body weight (maximum 2.5 g/day) orally once daily followed by chronic suppressive therapy
For Severe Disease, Add:
  • Rifabutin 10–20 mg/kg body weight (maximum 300 mg/day) orally once daily 
If Intolerant to Clarithromycin:
  • Azithromycin 10–12 mg/kg body weight (maximum 500 mg/day) orally once daily 
If Rifabutin Cannot Be Administered and a Third Drug is Needed in Addition to a Macrolide and Ethambutol, or if a Fourth Drug is Needed in Addition to Rifabutin for Patients with More Severe Symptoms or Disseminated Disease: 
  • Ciprofloxacin 10–15 mg/kg orally twice daily (maximum 1.5 g/day), or 
  • Levofloxacin 500 mg daily once daily, or
  • Amikacin 15–30 mg/kg body weight IV in 1 or 2 divided doses (maximum 1.5 g/day) 
Combination therapy with a minimum of 2 drugs is recommended for at least 12 months.

Clofazimine is associated with increased mortality in HIV-infected adults and should not be used. 

Children receiving ethambutol who are old enough to undergo routine eye testing should have monthly monitoring of visual acuity and color discrimination. 

Fluoroquinolones (e.g., ciprofloxacin and levofloxacin) are not labeled for use in children aged <18 years because of concerns regarding potential effects on cartilage; use in younger individuals requires an assessment of potential risks and benefits 

Chronic suppressive therapy (secondary prophylaxis) is recommended in children and adults following initial therapy.
Key to Acronyms: cART = combination antiretroviral therapy; CD4 = CD4 T lymphocyte; MAC = Mycobacterium avium Complex; IV = intravenous

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