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

Body
Table 2. Secondary Prophylaxis of Opportunistic Infections in Children with and Exposed to HIV — Summary of Recommendations
IndicationFirst ChoiceAlternativeComments/Special IssuesLast Reviewed
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 
November 6, 2013
Candidiasis

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

Fluconazole

  • Fluconazole 6–12 mg/kg body weight (maximum 600 mg/dose) by mouth three times weekly

Fluconazole 

  • Fluconazole 6–12 mg/kg body weight daily (maximum 200 mg) by mouth, or itraconazole oral solution, 2.5 mg/kg body weight/dose twice daily

Secondary Prophylaxis Indicated

  • Frequent or severe recurrences
  • Limited data in children

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
January 31, 2019
CoccidioidomycosisFluconazole 6 mg/kg body weight (maximum 400 mg) by mouth once dailyItraconazole 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%.November 6, 2013
CryptococcosisaFluconazole 6 mg/kg body weight (maximum 200 mg) by mouth once dailyItraconazole oral solution 5 mg/kg body weight (maximum 200 mg) by mouth once daily 

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 cART for >3 months

Criteria for Restarting Secondary Prophylaxis 

  • CD4 count <100/mm3

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

November 6, 2013
CryptosporidiosisN/AN/AN/AAugust 29, 2019
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 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 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
  • Consultation with opthamologist (if retinitis)
    • 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
August 3, 2023
GiardiasisN/AN/AN/AAugust 22, 2019
Hepatitis B Virus
(HBV)
Hepatitis A VaccineN/A

Secondary Prophylaxis Indicated or—

  • Chronically HBV-infected individuals to prevent further liver injury.

Criteria for Discontinuing Secondary Prophylaxis

  • N/A

Criteria for Discontinuing Secondary Prophylaxis

  • N/A
November 6, 2013
Hepatitis C Virus
(HCV)
NoneN/AN/ANovember 6, 2013
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 HSV Disease (Skin, Eye, CNS, or Disseminated 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 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.
June 27, 2018
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 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.

November 6, 2013
Human Papillomavirus (HPV)N/AN/AN/ANovember 6, 2013
Isosporiasis
(Cystoisosporiasis)

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
Consider discontinuing secondary prophylaxis in patients without evidence of active Isospora infection who have sustained improvement in immunologic status (from CDC immunologic category 3 to CD4 values that fall within category 1 or 2) for >6 months in response to ART.

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 data exist for dosing in children. Thus, the recommended dose for secondary prophylaxis in children is pyrimethamine 1 mg/kg (maximum 25 mg) by mouth once daily.

Ciprofloxacin is not a drug of choice in children because of increased incidence of adverse events, including events related to joints and/or surrounding tissues.
February 8, 2019
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/AThis 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
November 6, 2013
Microsporidiosis

Disseminated, Non-ocular Infection or GI Infection 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 QID (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
N/A

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) 
     
December 15, 2016
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 (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
January 8, 2019
Mycobacterium TuberculosisN/AN/AN/ASeptember 14, 2023
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:

  • 1,500 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 
November 6, 2013
SyphilisN/AN/A

Secondary Prophylaxis Indicated for—

  • N/A

Criteria for Discontinuing Secondary Prophylaxis

  • N/A

Criteria for Restarting Secondary Prophylaxis

  • N/A
November 6, 2013
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 three 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 for—

  • 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
November 6, 2013
Varicella-Zoster
Virus (VZV)
N/AN/AThere is no indication for secondary prophylaxisDecember 9, 2019
Key to Acronyms: BID = twice daily; BSA = body surface area; cART = combination antiretroviral therapy; CD4 = CD4 T lymphocyte; CDC = Centers of Disease Control and Prevention; CNS = central nervous system; CrCl = (estimated) creatinine clearance, CSF = cerebrospinal fluid; GI = gastrointestinal; HBV = hepatitis B virus; HCV = hepatitis C virus; HSV = herpes simplex virus; IV = intravenous; IVIG = intravenous immunoglobulin; MAC = mycobacterium avium complex; PCP = pneumocystis pneumonia; QID = four times a day; SQ = subcutaneous; TE = toxoplasmic encephalitis; TID = three times daily; TMP-SMX = trimethoprim-sulfamethoxazole

 

Back