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.

Tables

Table 1. Primary Prophylaxis

Last Updated: July 26, 2018; Last Reviewed: July 26, 2018

Table 1: Primary Prophylaxis
Indication First choice Alternative Comments/Special Issues Last Reviewed
Bacterial Infections
(S. pneumoniae and other invasive bacteria)
  • Pneumococcal, Meningococcal and Hib vaccines
  • Intravenous immune globulin (400 mg/kg body weight every 2 to 4 weeks)
  • TMP-SMX, 75/375 mg/m2 body surface area per dose by mouth twice daily
See Figures 1 and 2 for detailed vaccines recommendations.

Vaccines Routinely Recommended for Primary Prophylaxis. Additional Primary Prophylaxis Indicated For:
  • Hypogammaglobulinemia (that is, IgG <400 mg/dL)
Criteria for Discontinuing Primary Prophylaxis:
  • Resolution of hypogammaglobulinemia
Criteria for Restarting Primary Prophylaxis:
  • Relapse of hypogammaglobulinemia
November 6, 2013
Candidiasis
  • Not routinely recommended
N/A N/A November 6, 2013
Coccidioidomycosis N/A N/A Primary prophylaxis not routinely indicated in children. November 6, 2013
Cryptococcosis
  • Not recommended
  • Not recommended
N/A November 6, 2013
Cryptosporidiosis
  • ARV therapy to avoid advanced immune deficiency
N/A N/A November 6, 2013
Cytomegalovirus (CMV)
  • Valganciclovir tablets 900 mg orally once daily with food for older children who can receive adult dose (based on their BSA)
  • Valganciclovir oral solution (50 mg/mL) at total dose in milligrams = 7 x BSA x CrCl (Use maximum CrCl 150 mL/min/1.73 m2 ) orally once daily with food for children age 4 months – 16 years (max. dose 900mg/day)
  Primary Prophylaxis can be considered for:
  • CMV antibody positivity and severe immunosuppression (CD4 count <50 cells/mm3 in children ≥6 years; CD4 percentage <5% in children <6 years)
Criteria for discontinuing primary prophylaxis:
  • CD4 count >100 cells/mm3 for children ≥6 years; CD4 percentage >10% in children <6 years
Criteria for considering restarting primary prophylaxis:
  • CD4 count <50 cells/mm3 in children ≥6 years; CD4 percentage <5% in children <6 years
November 6, 2013
Giardiasis
  • cART to avoid advanced immunodeficiency
N/A N/A November 6, 2013
Hepatitis B Virus (HBV)
  • Hepatitis B Vaccine
  • Combination of hepatitis B immunoglobulin and hepatitis B vaccine to infants born to mothers with hepatitis B infection
  • Hepatitis B immunoglobulin following exposure
See Figs. 1 and 2 for detailed vaccines recommendations.

Primary Prophylaxis indicated for: All individuals who are not HBV infected

Criteria for discontinuing primary prophylaxis:
N/A

Criteria for restarting primary prophylaxis: N/A
November 6, 2013
Hepatitis C Virus (HCV)
  • None
N/A N/A November 6, 2013
Herpes Simplex Virus Infections (HSV) N/A N/A Primary prophylaxis not indicated November 6, 2013
Histoplasmosis N/A N/A Primary Prophylaxis indicated for: selected HIV-infected adults but not children.

Criteria for discontinuing primary prophylaxis: N/A

Criteria for restarting primary prophylaxis: N/A

November 6, 2013
Human Papillomavirus (HPV) HPV vaccine N/A See Figs. 1 and 2 for detailed vaccines recommendations. November 6, 2013
Influenza A and B Oseltamivir
Aged <3 Months:
  • Not recommendeda
Aged 3 Months to <1 Year:
  • 3 mg/kg body weight/dose once dailya
Aged ≥1 Year to 12 Years; Weight-Band Dosing:a
  • Weighing ≤15 kg: 30 mg once daily
  • Weighing >15 kg to 23 kg: 45 mg once daily
  • Weighing >23 kg to 40 kg: 60 mg once daily
  • Weighing >40 kg: 75 mg once daily
Aged ≥13 Years:
  • 75 mg once daily
Zanamivir (Aged ≥5 Years):
  • 10 mg (2 inhalations) once dailyb

None

Pre-Exposure Chemoprophylaxis
Indications:
  • After careful consideration of risks and benefits, pre-exposure antiviral chemoprophylaxis may be considered for children with HIV with severe immunosuppression while influenza virus is circulating in the community.
Duration:
  • When employed, pre-exposure antiviral chemoprophylaxis should continue for the duration of influenza virus circulation in the community.
Post-Exposure Chemoprophylaxis
Indications Recommended For:
  • Children with HIV with severe immunosuppression regardless of influenza vaccination status.
  • Children with HIV with moderate to no immunosuppression if
    • Influenza vaccination is contraindicated or unavailable; or
    • Low influenza vaccine effectiveness is documented in the current influenza season; and
    • Antiviral chemoprophylaxis can be started within 48 hours of exposure to an ill person with confirmed or suspected influenza.
Duration:
Note: Duration of chemoprophylaxis depends on the type of exposure, whether influenza vaccination was provided after the exposure, and whether influenza vaccine is anticipated to be effective based on the child’s degree of immunosuppression and the degree of match with circulating influenza viruses.
  • If influenza vaccination is provided after contact, chemoprophylaxis duration should be 2 weeks after vaccination.
  • If exposure is to a household contact, chemoprophylaxis duration should be 7 days.
  • If chemoprophylaxis is provided in setting of an institutional outbreak, the duration is either 14 days or 7 days after onset of symptoms in the last person infected, whichever is longer.c
Oseltamivir Dosing Adjustments
Premature Infants:
  • Current weight-based dosing recommendations for oseltamivir are not appropriate for premature infants (i.e., gestational age at delivery <38 weeks).d
Renal Insufficiency:
  • A reduction in dose of oseltamivir is recommended for patients with CrCl <30 mL/min. For patients with CrCl 10–30 mL/min, a reduction in chemoprophylaxis dosing frequency to every other day is recommended. PK data are limited for dosing recommendations for patients with severe renal insufficiency on dialysis.

a Oseltamivir is FDA-approved for prophylaxis of influenza in children aged ≥1 year. It is not approved for prophylaxis in children aged <1 year. However, CDC recommends that health care providers who treat children aged ≥3 months to <1 year administer a chemoprophylaxis dose of oseltamivir 3 mg/kg body weight/dose once daily. Chemoprophylaxis for infants aged <3 months is not recommended unless the exposure situation is judged to be critical.

b Zanamivir is not recommended for chemoprophylaxis in children aged <5 years or for children with underlying respiratory disease.

c See Fiore 2011 and Influenza Antiviral Medications: Summary for Clinicians for further details.

d See Acosta et al. J Infect Dis 2010; 202:563-566 for dosing recommendations in premature infants.

July 17, 2018
Isosporiasis (Cystoisosporiasis)
  • There are no U.S. recommendations for primary prophylaxis of isosporiasis
N/A
  • Initiation of cART to avoid advanced immunodeficiency may reduce incidence; TMP-SMX prophylaxis may reduce incidence.
November 6, 2013
Malaria For Travel To Chloroquine-Sensitive Areas:
  • Chloroquine base 5 mg/kg body weight base by mouth, up to 300 mg once weekly (equivalent to 7.5 mg/kg body weight chloroquine phosphate). Start 1–2 weeks before leaving, take weekly while away, and then take once weekly for 4 weeks after returning home
  • Atovaquone/proguanil once daily started 1–2 days before travel, for duration of stay, and then for 1 week after returning home
  • 11–20 kg; 1 pediatric tablet (62.5 mg/25 mg)
  • 21–30 kg, 2 pediatric tablets (125 mg/50 mg)
  • 31–40 kg; 3 pediatric tablets (187.5 mg/75 mg)
  • >40 kg; 1 adult tablet (250 mg/100 mg)
  • Doxycycline 2.2 mg/kg body weight (maximum 100 mg) by mouth once daily for children aged ≥8 years. Must be taken 1-2 days before travel, daily while away, and then up to 4 weeks after returning
  • Mefloquine 5 mg/kg body weight orally given once weekly (max 250 mg)
For Areas with Mainly P. Vivax:
  • Primaquine phosphate 0.6 mg/kg body weight base once daily by mouth, up to a maximum of 30 mg base/day. Starting 1 day before leaving, taken daily, and for 3–7 days after return
For Travel to Chloroquine-Resistant Areas:
  • Atovaquone/proguanil once daily started 1–2 days before travel, for duration of stay, and then for 1 week after returning home
    • 11–20 kg; 1 pediatric tablet (62.5 mg/25 mg)
    • 21–30 kg; 2 pediatric tablets (125 mg/50 mg)
    • 31–40 kg; 3 pediatric tablets (187.5 mg/75 mg)
    • >40 kg; 1 adult tablet (250 mg/100 mg)
  • Doxycycline 2.2 mg/kg body weight (maximum 100 mg) by mouth once daily for children aged ≥8 years. Must be taken 1–2 days before travel, daily while away, and then up to 4 weeks after returning
  • Mefloquine 5 mg/kg body weight orally given once weekly (maximum 250 mg)
N/A Recommendations are the same for HIV-infected and HIV-uninfected children. Please refer to the following website for the most recent recommendations based on region and drug susceptibility: http://www.cdc.gov/malaria/

For travel to chloroquine-sensitive areas. Equally recommended options include chloroquine, atovaquone/proguanil, doxycycline (for children aged ≥8 years), and mefloquine; primaquine is recommended for areas with mainly P. vivax.

G6PD screening must be performed prior to primaquine use.

Chloroquine phosphate is the only formulation of chloroquine available in the United States; 10 mg of chloroquine phosphate = 6 mg of chloroquine base.

For travel to chloroquine-resistant areas, preferred drugs are atovaquone/proguanil, doxycycline (for children aged ≥8 years) or mefloquine.
November 6, 2013
Microsporidiosis N/A N/A Not recommended December 14, 2016
Mycobacterium avium Complex (MAC)
  • Clarithromycin 7.5 mg/kg body weight [max 500 mg] by mouth orally twice daily, or
  • Azithromycin 20 mg/kg body weight [max 1200 mg] orally once weekly
  • Azithromycin 5 mg/kg body weight [max 250 mg] orally once daily
  • Children aged >5 years: rifabutin 300 mg orally once daily with food
Primary prophylaxis indicated for children:
  • Age <1 yr with CD4 count <750 cells/mm3
  • Age 1- 2 yrs with CD4 count <500 cells/mm3;
  • Age 2- 5 yrs with CD4 count <75 cells/mm3;
  • Age >5 yrs 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:
    • Age 2- 5 years with CD4 count >200 cells/mm3 for >3 consecutive months
    • Age >5 years with CD4 count >100 cells/mm3 for >3 consecutive months
Criteria for restarting primary prophylaxis:
  • Age 2- 5 years with CD4 count <200 cells/mm3
  • Age ≥6 years with CD4 count <100 cells/mm3
November 6, 2013
Mycobacterium Tuberculosis Source case drug susceptible:
  • Isoniazid, 10–15mg/kg body weight (max 300mg/day) by mouth daily for 9 months
Source case drug resistant:
  • Consult expert and local public health authorities
  • If adherence with daily isoniazid cannot be ensured, then isoniazid 20–30mg/kg body weight (max 900mg/day) by mouth 2x weekly by DOT for 9 months can be considered
  • Isoniazid 10-15mg/kg body weight (max 300mg/day) and rifampin 10-20mg/kg/body weight (max 600mg/day) by mouth daily for 3-4 mos
  • Rifampin, 10–20mg/kg body weight (max 600mg/day) by mouth daily for 4 to 6 mos
Drug-drug interactions with ART should be considered for all rifamycin containing alternatives

Indicated when:
  • Positive tuberculin skin test (TST ≥5 mm) or IGRA without previous TB treatment
  • Close contact with any infectious TB case. (Repeated exposures warrant repeated post-exposure prophylaxis)
  • TB disease must be excluded before starting treatment.
Criteria for discontinuing prophylaxis:
  • Only with documented severe adverse event, which is exceedingly rare
Adjunctive treatment:
  • Pyridoxine 1-2mg/kg body weight once daily (max: 25-50 mg/day) with isoniazid; pyridoxine supplementation is recommended for exclusively breastfed infants and for children and adolescents on meat- and milk-deficient diets; children with nutritional deficiencies, including all symptomatic HIV-infected children; and pregnant adolescents and women
November 6, 2013
Pneumocystis jirovecii Pneumonia
  • TMP–SMX (Cotrimoxazole): Trimethoprim (2.5-5 mg/kg body weight/dose) with sulfamethoxazole (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 trimethoprim and 1600 mg sulfamethoxazole. 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
November 6, 2013
Syphilis N/A N/A Primary prophylaxis indicated for: N/A

Criteria for discontinuing primary prophylaxis: N/A

Criteria for restarting primary prophylaxis: N/A

November 6, 2013
Toxoplasmosis TMP-SMX, 150/750 mg/m2 body surface area once daily by mouth For Children Aged ≥1 Month:
  • Dapsone 2 mg/kg body weight or 15 mg/m2 body surface area (maximum 25 mg) by mouth once daily, plus
  • Pyrimethamine 1 mg/kg body weight (maximum 25 mg) by mouth once daily, plus
  • Leucovorin 5 mg by mouth every 3 days
For Children Aged 1–3 Months and >24 Months:
  • Atovaquone 30 mg/kg body weight by mouth once daily
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
Acceptable Alternative Dosage Schedules for TMP-SMX:
  • TMP-SMX 150/750 mg/m2 body surface area per dose once daily by mouth 3 times weekly on 3 consecutive days per week TMP-SMX 75/375 mg/m2 body surface area per dose twice daily by mouth every day TMP-SMX 75/375 mg/m2 body surface area per dose twice daily by mouth 3 times weekly on alternate days
Primary prophylaxis indicated for:
IgG Antibody to Toxoplasma and Severe Immunosuppression:
  • HIV-infected children aged <6 years with CD4 percentage <15%; HIV-infected children aged ≥6 years with CD4 count <100 cells/mm3
Criteria for Discontinuing Primary Prophylaxis:
Note: Do not discontinue in children aged <1 year
  • After ≥6 months of cART, and
  • Aged 1 to <6 years; CD4 percentage is ≥15% for >3 consecutive months
  • Aged ≥6 years; CD4 count >200 cells/mm3 for >3 consecutive months
Criteria for Restarting Primary Prophylaxis:
  • Aged 1 to <6 years with CD4 percentage <15%
  • Aged ≥6 years with CD4 count <100 to 200 cells/mm3
November 6, 2013
Varicella-Zoster Virus (VZV)

Pre-Exposure Prophylaxis
Varicella vaccine N/A See Figures 1 and 2 for detailed vaccine recommendations. November 6, 2013
Varicella-Zoster Virus (VZV)

Primary (PostExposure) Prophylaxis
VariZIG 125 IU/10 kg body weight IM (maximum 625 IU), administered ideally within 96 hours (potentially beneficial up to 10 days) after exposure If VariZIG cannot be administered within 96 hours (up to 10 days), IVIG 400 mg/kg body weight, administered once should be considered. IVIG should ideally be administered within 96 hours of exposure

When passive immunization is not possible, some experts recommend prophylaxis with acyclovir 20 mg/kg body weight/ dose (maximum dose 800 mg), administered QID for 7 days, beginning 7–10 days after exposure
Primary Post-Exposure Prophylaxis Indicated for:

  • Patients with substantial exposure to varicella or zoster with no verified history of varicella or zoster or who are seronegative for VZV on a sensitive, specific antibody assay or who lack evidence of vaccination. Many experts limit this recommendation to varicella or zoster-exposed HIV-infected children who are considered to be severely immunocompromised, (i.e., in CDC Immunologic Category 3), especially if also classified as CDC Clinical Category Ca and experiencing a high HIV RNA plasma viral load (BIII).
  • Some experts start acyclovir at first appearance of rash.
Note: To obtain VariZIG, contact FFF Enterprises at 1-800-843-7477 or http://www.fffenterprises.com.

a CDC. Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. Official authorized addenda: human immunodeficiency virus infection codes and official guidelines for coding and reporting ICD-9-CM. MMWR Morb Mortal Wkly Rep. 1994;43:1-19. Available at https://www.cdc.gov/mmwr/PDF/rr/rr4312.pdf
November 6, 2013

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