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.

Hepatitis B Virus

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

Panel's Recommendations for Hepatitis B Virus
Panel's Recommendations
  • All pregnant women should be tested for hepatitis B surface antigen (HBsAg) during an early prenatal visit (AI). Testing should be repeated in late pregnancy for HBsAg-negative women at high risk of hepatitis B virus (HBV) infection (e.g., injection-drug users, women with intercurrent sexually transmitted diseases, women with multiple sex partners) (BIII).
  • All infants born to HBsAg-positive women, including HIV-co-infected women, should receive hepatitis B vaccine and hepatitis B immune globulin within 12 hours after birth, a second dose of hepatitis B vaccine at age 1 to 2 months, and a third dose at age 6 months (AI)
  • HIV-infected infants, children, and adolescents should be tested for HBsAg as soon as possible after HIV diagnosis (AII).
  • HIV-infected infants, children, and adolescents should be tested for quantitative anti-HBs and HBsAg 1 to 2 months after completing the vaccination series. If anti-HBs levels are <10 mIU/mL and the HBsAg result is negative, they should be revaccinated with a second, 3-dose series of HBV vaccine followed in 1 to 2 months by repeat testing for anti-HBs (AIII).
  • Antiviral therapy is not warranted in children without necroinflammatory liver disease (BIII). Treatment is not recommended for children with immunotolerant chronic HBV infection (i.e, HBeAg positive, normal serum transaminase levels despite detectable HBV DNA) or inactive carriers (i.e. HBeAg negative, normal serum transaminase levels despite detectable HBV DNA) (BII)
  • Indications for treatment of chronic HBV infection in HIV-co-infected children are the same as in HBV-infected and HIV-uninfected children: 
    • Evidence of ongoing HBV viral replication, as indicated by serum HBV DNA (>10,000–100,000 international units/ml for >6 months) and persistent elevation of serum transaminase levels (at least twice the upper limit of normal for >6 months), or 
    • Evidence of chronic hepatitis on liver biopsy (BII)
  • Standard interferon-alfa (IFN-α), IFN-2a or IFN-2b, is recommended for treating chronic HBV infection with compensated liver disease in HIV-uninfected children aged ≥2 years to <12 years who warrant treatment (AI). IFN-α therapy or oral antiviral therapy with adefovir or tenofovir is recommended for treating chronic HBV infection with compensated liver disease in HIV-uninfected children aged ≥12 years (AI). IFN-α therapy in combination with oral antiviral therapy cannot be recommended for pediatric HBV infection in HIV-uninfected children until more data are available (BII)
  • In HIV/HBV coinfected children who do not require combination antiretroviral therapy (cART) for their HIV infection, IFN-α therapy is the preferred agent to treat chronic hepatitis B (BIII), whereas adefovir can be considered in children age 12 years or older (BIII).
  • Treatment options for HIV/HBV co-infected children who meet criteria for HBV therapy and who are already receiving lamivudine- or emtricitabine-containing, HIV-suppressive cART include standard IFN- α therapy (BIII), or adefovir if the child can receive adult dosing (BIII), or use of tenofovir disoproxil fumarate (tenofovir) (with continued lamivudine or emtricitabine) in the cART regimen in children aged ≥2 years (BIII)
  • HIV/HBV-coinfected children should not be given lamivudine or emtricitabine for treatment of chronic HBV unless accompanied by additional anti-HIV drugs in a cART regimen (CIII).
  • For HIV/HBV-coinfected children who require treatment of both infections, a cART regimen that includes lamivudine (or emtricitabine) is recommended (BIII)
  • For HIV/HBV-coinfected children aged ≥ 2 years who require treatment for HIV but not HBV infection or treatment for both infections, a cART regimen that includes tenofovir and an anti-HBV nucleoside (either lamivudine or emtricitabine) can be considered (BIII).
  • The dose of lamivudine required to treat HIV infection is higher than that used to treat pediatric chronic hepatitis B infection; therefore, the higher dose of lamivudine should be used in HIV/HBV-coinfected children to avoid development of lamivudine-resistant HIV (AIII).
  • Lamivudine and emtricitabine should be considered interchangeable for treatment of chronic hepatitis B and not additive (BIII)
  • For hepatitis B e antigen (HBeAg)-positive patients who are HIV-uninfected, treatment with anti-HBV drugs should be continued until HBeAg seroconversion has been achieved and >6 months of additional treatment has been completed after the appearance of anti-HBeAg (BI*). However, treatment with lamivudine or other anti-HBV drugs with anti-HIV activity should be continued indefinitely in children with HIV/HBV infecco-infection, even if HBeAg seroconversion occurs (CIII).
  • If discontinuation of therapy for chronic HBV results in hepatic flare, therapy for chronic HBV infection should be reinstituted (BIII).
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 Prevention and Treatment of HBV in HIV/HBV Coinfected Children
Indication First Choice Alternative Comments/Special Issues
Primary Prophylaxis
  • Hepatitis B vaccine
  • Combination of hepatitis B immunoglobulin and hepatitis B vaccine for infants born to mothers with hepatitis B infection
Hepatitis B immunoglobulin following exposure
See Figures 1 and 2 for detailed vaccine 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
Secondary Prophylaxis
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
Treatment Treatment of Only HBV Required (Child Does Not Require cART):
  • IFN-α 3 million units/m2 body surface area SQ 3 times a week for 1 week, followed by dose escalation to 6 million units/m2 body surface area (max 10 million units/dose), to complete a 24-week course, or
  • For children aged ≥12 years, adefovir 10 mg by mouth once daily for a minimum of 12 months (uncertain if risk of HIV resistance)

Treatment of Both HIV And HBV Required (Child Not Already Receiving 3TC or FTC)

  • 3TC 4 mg/kg body weight (maximum 150 mg) per dose by mouth twice daily as part of a fully suppressive cART regimen
  • For children aged ≥2 years, include TDF as part of cART regimen with 3TC or FTC. For children aged ≥12, TDF dose is 300 mg once daily. For children aged <12 year, and 8 mg/kg body weight per dose once daily (maximum dose 300 mg) 
Treatment of Both HIV and HBV Required (Child Already Receiving cART Containing 3TC or FTC, Suggesting 3TC/FTC Resistance):
  • For children aged ≥2 years, include TDF as part of cART regimen with 3TC or FTC. For children aged ≥12 years, TDF dose is 300 mg once daily. For children aged <12 years, 8 mg/kg body weight per dose once daily (maximum dose 300 mg) 
  • For children aged ≥12 years, add adefovir 10 mg by mouth once daily or entecavir 0.5 mg by mouth once daily in addition to cART regimen.
  • For children aged <12 years, give 6-month course of IFN-α as above in addition to cART regimen.
  • IFN-α 10 million units/m2 body surface area SQ 3 times a week for 6 months (sometimes used for retreatment of failed lower-dose interferon therapy)
  • Alternative for 3TC: FTC 6 mg/kg body weight (maximum 200 mg) once daily
Indications for Treatment Include:
  • Detectable serum HBV DNA, irrespective of HBeAg status, for >6 months; and
  • Persistent (>6 months) elevation of serum transaminases (≥ twice the upper limit of normal); or
  • Evidence of chronic hepatitis on liver biopsy
IFN-α is contraindicated in children with decompensated liver disease; significant cytopenias, severe renal, neuropsychiatric, or cardiac disorders; and autoimmune disease. 

Choice of HBV treatment options for HIV/HBV-co-infected children depends upon whether concurrent HIV treatment is warranted.

3TC and FTC have similar activity (and have cross-resistance) and should not be given together. FTC is not FDA-approved for treatment of HBV.

TDF is approved for use in treatment of HIV infection in children aged ≥2 years but it is not approved for treatment of HBV infection in children aged <12 years. It should only be used for HBV in HIV/HBV-infected children as part of a cART regimen.

Adefovir is approved for use in children aged ≥12 years. 

ETV is not approved for use in children younger than age 16 years, but is under study in HIV-uninfected children for treatment of chronic hepatitis B. Can be considered for older HIV-infected children who can receive adult dosage. It should only be used for HBV in HIV/HBV-infected children who also receive an HIV-suppressive cART regimen.

IRIS may be manifested by dramatic increase in transaminases as CD4 cell counts rise within the first 6 to 12 weeks of cART. It may be difficult to distinguish between drug-induced hepatotoxicity and other causes of hepatitis and IRIS.

In children receiving TDF and 3TC or FTC, clinical and laboratory exacerbations of hepatitis (flare) may occur if the drug is discontinued; thus, once anti-HIV/HBV therapy has begun, it should be continued unless contraindicated or until the child has been treated for >6 months after HBeAg seroconversion and can be closely monitored on discontinuation. 

If anti-HBV therapy is discontinued and a flare occurs, reinstitution of therapy is recommended because a flare can be life threatening.

Telbivudine has been approved for use in people aged ≥16 years with HBV; there are no data on safety or efficacy in children aged <16 years; a pharmacokinetic study is under way in HIV-uninfected children.
Key to Acronyms: 3TC = lamivudine; cART = combined antiretroviral therapy; CD4 = CD4 T lymphocyte; FTC = emtricitabine; HBeAg = hepatitis B  antigen; HBV = hepatitis B virus; IFN-α = interferon alfa; IRIS = immune reconstitution inflammatory syndrome; SQ = subcutaneous; TDF = tenofovir disoproxil fumarate

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