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. Author manuscript; available in PMC: 2014 Nov 1.
Published in final edited form as: Pediatr Infect Dis J. 2013 Nov;32(0 2):i–KK4. doi: 10.1097/01.inf.0000437856.09540.11

Table 2.

Secondary Prophylaxis of Opportunistic Infections in HIV-Exposed and HIV-Infected Children—Summary of Recommendations (Last updated November 6, 2013; last reviewed November 6, 2013)

Indication First Choice Alternative Comments/Special Issues
Bacterial Infections S. pneumoniae and other invasive bacteria

  • TMP-SMX 75/375 mg/m2 body surface area per dose by mouth twice daily

  • IVIG 400 mg/kg body weight every 2–4 weeks

 Secondary Prophylaxis Indicated:

  • >2 serious bacterial infections in a 1-year period in children who are unable to take cART

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:

  • >2 serious bacterial infections in a 1-year period despite cART
Candidiasis Not routinely recommended, but can be considered for frequent severe recurrences.

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

 N/A Secondary Prophylaxis Indicated:

  • Frequent or severe recurrences

Criteria for Discontinuing Secondary Prophylaxis:

  • When CD4 count or percentage has risen to CDC immunologic Category 2 or 1

Criteria for Restarting Secondary Prophylaxis:

  • Frequent severe recurrences
Coccidioidomycosis Fluconazole 6 mg/kg body weight (maximum 400 mg) by mouth once daily Itraconazole 2–5 mg/kg body weight (maximum 200 mg) by mouth per dose twice daily Lifelong secondary prophylaxis with fluconazole for patients with meningitis or disseminated disease in the immunocompromised patient is recommended. Secondary prophylaxis should be considered after treatment of milder disease if CD4 count remains <250 cells/mm3 or CD4 percentage <15%.
Cryptococcosisa Fluconazole 6 mg/kg body weight (maximum 200 mg) by mouth once daily Itraconazole oral solution 5 mg/kg body weight (maximum 200 mg) by mouth once daily Secondary Prophylaxis Indicated:

  • Documented disease

Criteria 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 cART for >3 months

Criteria for Restarting Secondary Prophylaxis:

  • CD4 count <100/mm3

a Secondary prophylaxis is also referred to as maintenance therapy or suppressive therapy.
Cryptosporidiosis N/A N/A N/A
Cytomegalovirus (CMV)

  • 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 × BSA × 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

If All of the Following Criteria Are Fulfilled:

  • Completed ≥6 months of cART

  • Consultation with ophthalmologist (if retinitis)

  • Age <6 years with CD4 percentage ≥15% for >6 consecutive months

  • Age ≥6 years with CD4 cell count >100 cells/mm3 for >6 consecutive months

  • For 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 cell count <100 cells/mm3
Giardiasis N/A N/A N/A
Hepatitis B Virus (HBV) Hepatitis A Vaccine N/A Secondary Prophylaxis Indicated for:

  • Chronically HBV-infected individuals to prevent further liver injury

Criteria for Discontinuing Secondary Prophylaxis:

  • N/A

Criteria for Restarting Secondary Prophylaxis:

  • N/A
Hepatitis C Virus (HCV) None N/A N/A
Herpes Simplex Virus (HSV) Infections Mucocutaneous Disease:

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





Suppressive Therapy After Neonatal Skin, Eye, Mouth, or CNS Disease:

  • Acyclovir 300 mg/m2 body surface area/dose by mouth TID for 6 months

 Mucocutaneous Disease, For Adolescents Old Enough to Receive Adult Dosing:

  • Valacyclovir 500 mg by mouth BID, or

  • Famciclovir 500 mg by mouth BID

 Secondary Prophylaxis Indicated:

  • 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.
Histoplasmosis (Suppressive Therapy) Itraconazole oral solution 5–10 mg/kg body weight (maximum 200 mg) per dose by mouth daily Fluconazole 3–6 mg/kg body weight (maximum 200 mg) by mouth once daily Secondary Prophylaxis Indicated:

  • 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.
Human Papillomavirus (HPV) N/A N/A N/A
Influenza N/A N/A No role for secondary chemoprophylaxis
Isosporiasis (Cystoisosporiasis) If Severe Immunosuppression:

  • Administer TMP-SMX 2.5 mg/kg body weight of TMP component twice daily by mouth 3 times per week

 Pyrimethamine 1 mg/kg body weight (maximum 25 mg) plus folinic acid, 10– 25 mg by mouth once daily.
Second-Line Alternative:

  • Ciprofloxacin, 10–20 mg/kg body weight given twice daily by mouth 3 times per week

 Consider discontinuing secondary prophylaxis in a patient receiving cART after sustained improvement from severe immunosuppression (from CDC immunologic category 3 to CD4 values that fall within category 1 or 2) for longer than 6 months.

In adults, the dose of pyrimethamine for secondary prophylaxis (25 mg daily) is lower than the dose for treatment (50–75 mg daily), but no similar data exist for children. Thus, the recommended dosing for secondary prophylaxis in children is 1 mg/kg per dose (maximum 25 mg) once daily.

Ciprofloxacin is generally not a drug of first choice in children due to increased incidence of adverse events, including events related to joints and/or surrounding tissues.
Malaria 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

 N/A This regimen, known as PART, is recommended only for individuals who have resided in a malaria-endemic area for an extended period of time. Adult dose: 30 mg base (52.6 mg salt) orally, daily for 14 days after departure from the malarious area.

http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-3-infectious-diseases-related-to-travel/malaria.htm#1939
Microsporidiosis Disseminated, Non-Ocular Infection or GI Infection Caused by Microsporidia Other Than E. Bieneusi or V. Corneae:

  • 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 QID (investigational use only in United States) plus albendazole 7.5 mg/kg body weight (maximum 400 mg/dose) by mouth twice daily for management of systemic infection

 N/A Criteria For Discontinuing Secondary Prophylaxis:

  • Continue until sustained immune reconstitution (more than 6 months at CDC immunologic category 1 or 2), or

  • After initiation of cART and resolution of signs and symptoms
Mycobacterium avium Complex (MAC) (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
Mycobacterium Tuberculosis N/A N/A N/A
Pneumocystis Pneumonia

  • 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)

 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
Syphilis N/A N/A Secondary Prophylaxis Indicated:

  • N/A

Criteria For Discontinuing Secondary Prophylaxis:

  • N/A

Criteria For Restarting Secondary Prophylaxis:

  • N/A
Toxoplasmosis (Suppressive Therapy)

  • Sulfadiazine 42.5–60 mg/kg body weight per dose twice daily* (maximum 2–4 g per day) by mouth, plus

  • Pyrimethamine 1 mg/kg body weight or 15 mg/m2 body surface area (maximum 25 mg) by mouth once daily, plus

  • Leucovorin 5 mg by mouth once every 3 days

  • Clindamycin 7–10 mg/kg body weight per dose by mouth 3 times daily, plus

  • Pyrimethamine 1 mg/kg body weight or 15 mg/m2 body surface area (maximum 25 mg) by mouth once daily, plus

  • Leucovorin 5 mg by mouth once every 3 days

Children Aged 1–3 Months and >24 Months:

  • Atovaquone 30 mg/kg body weight by mouth once daily

  • Leucovorin, 5 mg by mouth every 3 days

  • TMP-SMX, 150/750 mg/m2 body surface area once daily by mouth

Children Aged 4–24 Months:

  • Atovaquone 45 mg/kg body weight by mouth once daily, with or without pyrimethamine 1 mg/kg body weight or 15 mg/m2 body surface area (maximum 25 mg) by mouth once daily, plus

  • Leucovorin, 5 mg by mouth every 3 days

  • TMP-SMX, 150/750 mg/m2 body surface area once daily by mouth

 Secondary Prophylaxis Indicated:

  • Prior toxoplasmic encephalitis

Note: Alternate regimens with very limited data in children. TMP-SMX only to be used if patient intolerant to other regimens

Criteria for Discontinuing Secondary Prophylaxis

If All of the Following Criteria are Fulfilled:

  • Completed ≥6 months of cART, completed initial therapy for TE, asymptomatic for TE, and

  • Aged 1 to < 6 years; CD4 percentage ≥15% for >6 consecutive months

  • Aged ≥6 years; CD4 cell count >200 cells/mm3 for >6 consecutive months

Criteria For Restarting Secondary Prophylaxis:

  • Aged 1 to <6 years with CD4 percentage <15%

  • Aged ≥6 years with CD4 cell count <200 cells/mm3
Varicella-Zoster Virus (VZV) N/A N/A There is no indication for secondary prophylaxis

Key to Acronyms: BID = twice daily; BSA = body surface area; cART = combination antiretroviral therapy; CNS = central nervous system; CrCl = (estimated) creatinine clearance, CSF = cerebrospinal fluid; GI = gastrointestinal; HBV = hepatitis B virus; HSV = herpes simplex virus; IV = intravenous; SQ = subcutaneous; TE = toxoplasmic encephalitis; TID = three times daily; TMP-SMX = trimethoprim-sulfamethoxazole