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.

Varicella-Zoster Virus

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

Panel's Recommendations for Varicella-Zoster Virus
Panel's Recommendations
  • HIV-infected children and adults who have no evidence of immunity to varicella should avoid exposure to people with varicella or zoster (AIII). Household contacts of HIV-infected patients should receive varicella vaccine if they lack evidence of immunity to avoid the possibility of transmitting wild-type varicella-zoster virus (VZV) to their HIV-infected contacts (AIII).
  • HIV-infected children aged 1 through 8 years without evidence of varicella immunity and whose CD4 T lymphocyte (CD4) cell counts are ≥15% should be considered for 2 doses of varicella vaccine, the first dose administered as early as age 12 to 15 months (or as soon as possible after the first birthday) and the second dose 3 months later (BII). Older children with comparable levels of immune function (i.e., CD4 cell counts ≥200 cells/mm3) who lack varicella immunity may be considered for 2 doses of varicella vaccine administered 3 months apart (BIII).
  • Combination measles-mumps-rubella-varicella vaccine should not be administered to HIV-infected children (AIII).
  • HIV-infected children with low CD4 percentages (<15%) should not be vaccinated against varicella (AIII). Vaccination of such children can be safely undertaken after reconstitution of their immune systems (CD4 percentage ≥15%) with combination antiretroviral therapy (cART) for at least 3 months (AII). Herpes zoster (HZ) vaccine should not be given to HIV-infected children (AIII).
  • HIV-infected children and adolescents who:
  1. lack evidence of immunity to varicella, and
  2. have a non-transient exposure to a contact with varicella or herpes zoster

should receive VZV immunoglobulin prophylaxis as soon as possible (ideally within 96 hours but potentially beneficial up to 10 days) after the close contact (AII). Many experts limit this recommendation to varicella- or zoster-exposed HIV-infected children who are considered to be severely immunocompromised (i.e., CDC Immunologic Category 3) especially if they have high HIV viral loads and would be classified in CDC Clinical Category C (BIII). When passive immunization is impossible, some experts recommend prophylaxis with acyclovir beginning 7 to 10 days after exposure, while others consider it prudent to wait until the first appearance of rash to start acyclovir therapy in VZV-susceptible and VZV-exposed, HIV-infected children (CIII).

  • Acyclovir is the drug of choice for treating VZV infection in HIV-infected children (AI). Intravenous (IV) acyclovir is recommended for treating varicella in HIV-infected children with severe immunosuppression (i.e., CDC Immunologic Category 3) and those who have high fever, abdominal pain, respiratory symptoms, or numerous or deep, necrotic, or hemorrhagic skin lesions (AIII). Oral acyclovir should only be used to treat varicella in HIV-infected children who are in CDC Immunologic Category 1 or 2 and who have mild varicella disease (BIII).
  • Acyclovir is the oral treatment of choice for zoster in HIV-infected children, given for 7 to 10 days, although longer durations of therapy should be considered if lesions are slow to resolve (AII*). Oral administration of acyclovir for HZ is considered safe for children with mild to moderate immune suppression (AII). Initial IV administration is recommended for HIV-infected children with severe immunosuppression (i.e., CDC Immunologic Category 3), extensive multidermatomal HZ, disseminated infection, visceral involvement, or otherwise complicated HZ (AII*). It can also be considered for trigeminal nerve or sacral dermatomal involvement. IV acyclovir should be continued until cutaneous lesions and visceral disease are clearly resolving (AIII), after which oral administration can be considered to complete the course of therapy—10 to 14 days in this situation (AIII).
  • Recommended treatment for progressive outer retinal necrosis includes optimization of cART and IV anti-VZV therapy that includes combinations of systemic antivirals (acyclovir or ganciclovir plus foscarnet), frequently with twice-weekly intravitreal injections of ganciclovir and/or foscarnet (AIII). Adjunctive retinal surgery is sometimes recommended, along with corticosteroids and/or low-dose aspirin (BIII). Acute retinal necrosis can be treated with IV acyclovir for 10 to 14 days, followed by prolonged (i.e., 4–6 weeks) oral treatment (AIII)
  • Alternatives to oral acyclovir in older adolescents include valacyclovir and famciclovir (AI*).
  • The treatment of choice for acyclovir-resistant VZV is IV foscarnet for 7 days (AII*) or until no new lesions for at least 48 hours (AIII).
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 Preventing and Treating Varicella-Zoster Virus
Indication First Choice Alternative Comments/Special Issues
Pre-Exposure Prophylaxis
Varicella vaccine
N/A
See Figures 1 and 2 for detailed vaccine recommendations.
Primary (Post-Exposure) 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 http://www.cdc.gov/mmwr/PDF/rr/rr4312.pdf.
Secondary Prophylaxis
N/A N/A There is no indication for secondary prophylaxis
Treatment
 
Chickenpox
Children with No or Moderate Immune Suppression (CDC Immunologic Categories 1 and 2) and Mild Varicella Disease:
  • Acyclovir 20 mg/kg body weight/dose by mouth (max 800 mg/dose) QID for 7–10 days and until no new lesions for 48 hours
Children with Severe Immune Suppression (CDC Immunologic Category 3):
  • Acyclovir 10 mg/kg body weight 500 mg/m2/dose IV every 8 hours for 7–10 days and until no new lesions for 48 hours
Zoster
Children with Uncomplicated Zoster:
  • Acyclovir 20 mg/kg body weight/dose (max 800 mg/dose) by mouth QID for 7–10 days.

Children with Severe Immunosuppression (CDC Immunologic Category 3), Trigeminal or Sacral Nerve Involvement, Extensive Multidermatomal, or Disseminated Zoster:

  • Acyclovir 10 mg/kg body weight/dose IV every 8 hours until cutaneous lesions and visceral disease are clearly resolving, then can switch to acyclovir by mouth to complete a 10 to 14-day course

Children with Progressive Outer Retinal Necrosis:

  • Ganciclovir 5 mg/kg body weight/dose IV every 12 hours, plus 
  • foscarnet 90 mg/kg body weight/dose IV) every 12 hours, plus 
  • ganciclovir 2 mg/0.05 mL intravitreal twice weekly and/or foscarnet 1.2 mg/0.05 mL intravitreal twice weekly

Children with ARN:

  • Acyclovir 10–15 mg/kg body weight/dose IV every 8 hours daily for 10–14 days, followed by

Oral valacyclovir 1 g/dose TID for 4–6 weeks (for children old enough to receive adult dose). Alternative oral acyclovir dose: 20 mg/kg body weight/dose QID for 4–6 weeks

Patients Unresponsive to Acyclovir:
  • Foscarnet (40–60 mg/kg body weight/dose IV every 8 hours) for 7-10 days or until no new lesions have appeared for 48 hours




In children ≥1 year of age, some experts base IV acyclovir dosing on body surface area (500 mg/m2 body surface area/dose IV every 8 hours) instead of body weight.

Valacyclovir is approved for use in adults and adolescents with zoster at 1 g/dose by mouth TID for 7 days; the same dose has been used for varicella infections. Data on dosing in children are limited and there is no pediatric preparation, although 500 mg capsules can be extemporaneously compounded to make a suspension to administer 20 mg/kg body weight/dose (maximum dose 1 g) given TID (see prescribing information).

Famciclovir is approved for use in adults and adolescents with zoster at 500 mg/dose by mouth TID for 7 days; the same dose has been used for varicella infections. There is no pediatric preparation and data on dosing in children are limited; can be used by adolescents able to receive adult dosing. 

Involvement of an ophthalmologist with experience in managing herpes zoster ophthalmicus and its complications in children is strongly recommended when ocular involvement is evident.

Optimal management of PORN has not been defined.

Key to Acronyms: ARN = acute retinal necrosis; CDC = Centers for Diseases Control and Prevention; IM = intramuscular; IU = international units; IV = intravenous; IVIG = intravenous immunoglobulin; PORN = progressive outer retinal necrosis; QID = four times a day; TID = three times daily; VariZIG = varicella zoster immune globulin; VZV = varicella zoster virus

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