Table 2. Secondary Prophylaxis of Opportunistic Infections in Children With and Exposed to HIV — Summary of Recommendations

Secondary Prophylaxis Indicated

• More than two serious bacterial infections in a 1-year period in children who are unable to take ART

Criteria for Discontinuing Secondary Prophylaxis

• Sustained (≥3 months) immune reconstitution (CD4 percentage ≥25% if ≤6 years old; CD4 percentage ≥20% or CD4 count >350 cells/mm³ if >6 years old) 

Criteria for Restarting Secondary Prophylaxis

• More than two serious bacterial infections in a 1-year period despite ART

Not routinely recommended but can be considered for frequent severe recurrences despite ART.

• Fluconazole 6 mg/kg body weight (maximum 200 mg/dose) PO three times weekly

• Fluconazole 3–6 mg/kg body weight PO daily (maximum 200 mg/day)
• Itraconazole oral solution, 2.5 mg/kg body weight/dose PO twice daily

Secondary Prophylaxis Indicated (Limited Data in Children)

• Frequent or severe recurrences despite ART
• In patients with initial fluconazole-refractory OPC or esophageal candidiasis that subsequently responded to voriconazole, posaconazole, or an echinocandin: may consider continuation of the effective drug until immune reconstitution

Criteria for Discontinuing Secondary Prophylaxis

• When CD4 count or percentage has risen to HIV stage 1 or 2 (see HIV Infection Stage Table)

Criteria for Restarting Secondary Prophylaxis 

• Frequent severe recurrences 

Lifelong secondary prophylaxis with fluconazole for immunocompromised patients with meningitis or disseminated disease is recommended.

Secondary prophylaxis should be considered after treatment of milder disease if CD4 count remains <250 cells/mm³ or CD4 percentage <15%.

Secondary Prophylaxis Indicated

• Documented disease 

Criterial for Discontinuing Secondary Prophylaxis

If All of the Following Criteria Are Fulfilled: 

• Age ≥6 years
• Asymptomatic on ≥12 months of secondary prophylaxis
• CD4 count ≥100 cells/mm³ with undetectable HIV viral load on ART for >3 months

Criteria for Restarting Secondary Prophylaxis 

• CD4 count <100/mm³

^aSecondary prophylaxis is also referred to as maintenance therapy or suppressive therapy.

• Ganciclovir 5 mg/kg body weight IV once daily; or
• For older children who can receive adult dose (based on their BSA), valganciclovir tablets 900 mg orally once daily with food, or
• For children age 4 months–16 years, valganciclovir oral solution 50 mg/mL (at dose in milligrams = 7 x BSA x CrCl up to maximum CrCl of 150 mL/min/1.73 m² orally once daily with food, or
• Foscarnet 90–120 mg/kg body weight IV once daily

• Cidofovir 5 mg/kg body weight per dose IV every other week. Must be given with probenecid and IV hydration.

Secondary Prophylaxis Indicated for—

• Prior disseminated disease, retinitis, neurologic disease, or GI disease with relapse. 

Criteria for Discontinuing Secondary Prophylaxis (All of the Following Criteria Must Be Fulfilled)

• Completed ≥6 months of ART
• Age <6 years with CD4 percentage ≥15% for >6 consecutive months
• Age ≥6 years with CD4 count >100 cells/mm³ for >6 consecutive months
• Consultation with ophthalmologist (if retinitis)

  • Routine (i.e., every 3–‍6 months) ophthalmological follow-up is recommended for early detection of relapse or immune restoration uveitis.

    Criteria for Restarting Secondary Prophylaxis

• Age <6 years with CD4 percentage <15%
• Age ≥6 years with CD4 count <100 cells/mm³

Secondary Prophylaxis Indicated for—

• Individuals with chronic HBV infection to prevent further liver injury.

Criteria for Discontinuing Secondary Prophylaxis

• N/A

Criteria for Restarting Secondary Prophylaxis

• N/A

Mucocutaneous Disease

• Acyclovir 20 mg/kg body weight/dose (maximum 800 mg/dose) by mouth twice daily

Suppressive Therapy After Neonatal HSV Disease (Skin, Eye, CNS, or Disseminated Disease)

• Acyclovir 300 mg/m² BSA/dose by mouth three times daily for 6 months

Mucocutaneous Disease, for Adolescents Old Enough to Receive Adult Dosing

• Valacyclovir 500 mg by mouth twice daily, or
• Famciclovir 500 mg by mouth twice daily 

Secondary Prophylaxis Indicated or—

• Suppressive secondary prophylaxis can be considered for children with severe and recurrent mucocutaneous (oral or genital) disease.

Criteria for Discontinuing Secondary Prophylaxis

• After a prolonged period (e.g., 1 year) of prophylaxis, consider suspending prophylaxis and determine with the patient whether additional prophylaxis is necessary. Although level of immune reconstitution is a consideration, no specific CD4 threshold has been established.

Secondary Prophylaxis Indicated for—

• Documented histoplasmosis in a patient with impaired immune function

Criteria for Discontinuing Secondary Prophylaxis 
If All of the Following Criteria Are Fulfilled:

• CD4 percentage >15% at any age; or CD4 cell count >150 cells/mm³ aged ≥6 years.
• Received ≥1 year itraconazole maintenance therapy
• Established (e.g., ≥6 months) adherence to effective cART
• Negative Histoplasma blood cultures
• Serum Histoplasma antigen <2 ng/mL 

Use same initial itraconazole dosing for capsules as for solution. Itraconazole solution is preferred to the capsule formulation because it is better absorbed; solution can achieve serum concentrations 30% higher than those achieved with the capsules.

If Several Immunosuppression—

• TMP-SMX 2.5 mg/kg body weight of the TMP component (maximum 80 mg TMP) twice daily by mouth three times per week

Pyrimethamine 1 mg/kg body weight (maximum 25 mg) plus folinic acid, 5–15 mg by mouth once daily.

Secondary-Line Alternative

• Ciprofloxacin, 10–20 mg/kg body weight (maximum 500 mg) by mouth three times per week

For P. vivax or P. ovale:

• Primaquine 0.5 mg/kg base (0.8 mg/kg salt) up to adult dose orally, daily for 14 days after departure from the malarious area

Disseminated, Non-ocular Infection or GI Infection Caused by Microsporidia Other Than E. bieneusi or V. cornea

• Albendazole 7.5 mg/kg body weight (maximum 400 mg/dose) by mouth twice daily 

Ocular Infection

• Topical fumagillin bicyclohexylammonium (Fumidil B) 3 mg/mL in saline (fumagillin 70 μg/mL) eye drops: 2 drops every 2 hours for 4 days, then 2 drops four times a day (investigational use only in United States) plus, for infection attributed to microsporidia other than E. bieneusi or V. corneae, albendazole 7.5 mg/kg body weight (maximum 400 mg/dose) by mouth twice daily for management of systemic infection

Criteria for Discontinuing Secondary Prophylaxis

• After initiation of ART, resolution of signs and symptoms and sustained immune reconstitution (more than 6 months at CDC immunologic category 1 or 2) 
   

• 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 (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

Secondary Prophylaxis Indicated for—

• Prior disease 

Criteria for Discontinuing Secondary Prophylaxis
Fulfillment of All of the Following Criteria: 

• Completed ≥6 months of ART
• Completed ≥12 months MAC therapy
• Asymptomatic for signs and symptoms of MAC
• Aged 2 to <6 years: CD4 count >200 cells/mm³ for ≥6 consecutive months
• Aged ≥6 years: CD4 count >100 cells/mm³ for ≥6 consecutive months

Criteria for Restarting Secondary Prophylaxis

• Aged 2 to <6 years: CD4 count <200 cells/mm³
• Aged ≥6 years: CD4 count <100 cells/mm³

• TMP-SMX: 5–‍10 mg/kg/DAY (TMP ‍‍component)
• Maximum individual dose: 160 mg/DOSE (TMP component).
• Several dosing regimens have been used successfully:
  • 3 days per week on consecutive or alternate days in divided doses every 12 hours
  • Daily as a single dose
  • Administration 2 days per week on consecutive or alternate days in doses divided every 12 hours has been used successfully in pediatric oncology patients.

Dapsone and atovaquone are both first-line alternatives (see text for relative risks and benefits), followed by aerosolized pentamidine as second line and IV pentamidine as third line.

Dapsone

• Children Aged ≥1 Month: 2 mg/kg/dose (maximum: 100 mg/dose) PO once daily or 4 mg/kg/dose (maximum 200 mg/dose) PO once weekly

Atovaquone

• Children Aged 1–3 Months or >24 Months to 12 Years: 30–‍40 mg/kg/dose PO once daily with food (maximum: 1,500 mg/dose)
• Children Aged 4–24 Months: 45 mg/kg/dose PO once daily with food (maximum: 1,500 mg/dose)
• Children Aged ≥13 Years: 1,500 mg PO once daily

Aerosolized Pentamidine Via Respirgard II Nebulizer

For Children Able to Comply With Its Use

• Children Aged <5 Years: Limited data regarding dosing. 9 mg/kg/dose or 150 mg/dose every month have been suggested.
• Children Aged ≥5 Years: 300 mg every month

IV Pentamidine

• 4 mg/kg/dose every 3 to 4 weeks; maximum dose: 300 mg/dose
• Limited data regarding dosing frequency; based on use in oncology patients

Secondary Prophylaxis Indicated for:

• Children with prior episode of PCP

Criteria for Discontinuing Secondary Prophylaxis

• Children Aged <1 Year: Continue primary prophylaxis in children with HIV throughout the first year of life
• Children Aged 1 Year and Older on ART for ≥6 Months With CD4 Count Above Age-Specific Stage 3 Cutoff for >3 Consecutive Months:
  • Children Aged 1 Year to <6 Years: ≥500 cells/mm³ or ≥22%
  • Children Aged ≥6 Years: ≥200 cells/mm³ or ≥14%
• Discontinuation can be considered in children ≥6 Years if on ART for ≥6 months with undetectable viral load and CD4 count 101–‍200 cells/mm³ if intolerant of prophylaxis medications

Criteria for Restarting Secondary Prophylaxis

• CD4 count below age-specific stage 3 cutoff (see above)

Secondary Prophylaxis Indicated for—

• N/A

Criteria for Discontinuing Secondary Prophylaxis

• N/A

Criteria for Restarting Secondary Prophylaxis

• N/A

• Sulfadiazine 85–120 mg/kg body weight per day in 2–4 divided doses (maximum 2–4 g per day) PO, plus
• Pyrimethamine 1 mg/kg body weight or 15 mg/m² BSA (maximum 25 mg) PO once daily, plus
• Leucovorin 5 mg PO once every 3 days

• Clindamycin 7–10 mg/kg body weight per dose (max 600 mg/dose) PO three times daily, plus
• Pyrimethamine 1 mg/kg body weight or 15 mg/m² BSA (maximum 25 mg) PO once daily, plus
• Leucovorin 5 mg PO once every 3 days

Children Aged 1–3 Months and >24 Months

• Atovaquone 30 mg/kg body weight PO (maximum 1,500 mg) once daily with food, plus
• TMP-SMX, 150/750 mg/m² BSA PO once daily

Children Aged 4–24 Months

Option 1

• Atovaquone 45 mg/kg body weight PO once daily with food, with or without
• Pyrimethamine 1 mg/kg body weight or 15 mg/m² BSA (maximum 25 mg) PO once daily, plus leucovorin (when using pyrimethamine), 5 mg PO every 3 days

Option 2

• Atovaquone 45 mg/kg body weight (maximum 1,500 mg) PO once daily with food, plus
• TMP-SMX, 150/750 mg/m² BSA PO once daily

Secondary Prophylaxis Indicated

• Prior TE

Note: Limited data in children is available for alternative regimens. TMP-SMX only to be used if individual is intolerant to other regimens.

Criteria for Discontinuing Secondary Prophylaxis

If All of the Following Criteria Are Fulfilled:

• Completed initial therapy for TE, and
• Asymptomatic for TE, and
• Aged ≥6 years old with CD4 >200 cells/mm³ in those or CD4% >22% (CD4 count >500 cells/mm³) in those aged 1–5 years for 3 consecutive months

Criteria for Restarting Secondary Prophylaxis:

• CD4 count ≤200 cells/mm³ and CD4% ≤22% (CD4 count ≤500 cells/mm³) in those aged 
  1–5 years

Note: Sulfadiazine may be given as 2–4 equal doses per day as long as the total daily dose is 85–120 mg/kg body weight.