Australasian Society for HIV Medicine

The 2008 updated ‘Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection' have been released and are available by following the link for (1). The guidelines address issues specific to the use of antiretroviral therapy for HIV-infected infants, children, and pre-pubertal adolescents. The Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, a working group of the Office of AIDS Research Advisory Council, reviews new data on an ongoing basis and provides regular updates to the guidelines, which are available by following the link (http://health.nih.gov/result.asp/15). Also available at this web site are updated guidelines for HIV-infected post-pubertal adolescents and adults. These guidelines were developed for the United States. The World Health Organization (WHO) provides guidelines for resource-limited settings, these are available by following the link at (2).

The 2008 updated Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection recommendations represent the current state of knowledge regarding the use of antiretroviral drugs in children, and are based on published and unpublished data regarding the treatment of HIV infection in infants, children, and adults and, when no definitive data were available, the clinical expertise of the Working Group members. The Working Group intends the guidelines to be flexible and not to replace the clinical judgment of experienced health care providers. Updates are highlighted in yellow.

The guidelines include the following updated recommendations by the Working Group:

1. Infants under age 18 months require virologic assays that directly detect HIV to diagnose HIV infection, since antibody assays cannot be used due to the persistence of maternal HIV antibody in this age group. Virologic diagnostic testing in infants with known perinatal HIV exposure is recommended at age 14-21 days; 1-2 months; and 4-6 months. Some experts also perform virologic testing at birth. Preferred virologic assays include HIV DNA PCR and HIV RNA assays. Many experts confirm the absence of HIV infection in infants with negative virologic tests by performing an antibody test at age 12-18 months to document sero-reversion to HIV antibody negative status.

2. Initiation of antiretroviral therapy is recommended for infants aged <12 months, regardless of clinical status, CD4 percentage, or viral load.

3. Women who have not been tested for HIV prior to or during labour should be offered rapid testing during the immediate postpartum period or their newborns should undergo rapid HIV antibody testing, with counselling and consent of the mother unless state law allows testing without consent. This allows initiation of antiretroviral prophylaxis soon after delivery for infants born to HIV-infected women, counselling of HIV-infected women not to breastfeed their infant, and linkage to HIV-related medical care and services for both mother and child.

4. In children under age 5 years, CD4 percentage is preferred for monitoring immune status because of age-related changes in absolute CD4 count in this age group.

5. Initiation of antiretroviral therapy is also recommended for children age ≥1 year who have met the age-related CD4 threshold for initiating treatment (CD4 <25% for children aged 1 to <5years and <350 cells/mm3 for children ≥5 years), regardless of symptoms or plasma HIV RNA level. Initiation of antiretroviral therapy should be considered for children age ≥1 year who are asymptomatic or have mild symptoms (clinical category N and A or the following clinical category B conditions: single episode of serious bacterial infection or lymphoid interstitial pneumonitis) and have CD4 ≥25% for children aged 1 to <5 years or ≥350 cells/mm3 for children ≥5 years and have plasma HIV RNA ≥100,000 copies/mL. Initiation of antiretroviral therapy may be deferred for children age ≥1 year who are asymptomatic or have mild symptoms and who have CD4 ≥25%% for children aged 1 to <5 years and ≥350 cell/mm3 for children ≥5 years and have plasma HIV RNA <100,000 copies/mL.

6. Infants who are identified as HIV-infected during the first 6 weeks of life while receiving zidovudine chemoprophylaxis should have zidovudine discontinued and initiate treatment with combination therapy with at least 3 drugs (with drug choice based on results from antiretroviral drug resistance testing and treatment only initiated following assessment and counseling of the caregivers regarding adherence to therapy).

7. The Working Group does not recommend the following NNRTI as initial therapy in children: Etravirine, due to lack of pediatric formulation and pediatric pharmacokinetic data, no efficacy or safety data in children, and lack of data in antiretroviral naive patients.

PI-Based Regimens (1 or 2 PIs + 2 NRTI backbone)

1. Preferred PI:

• Lopinavir/ritonavir in combination with 2 NRTIs

2. Alternative PI:

• Fosamprenavir in combination low dose ritonavir and 2 NRTIs (for children age >6 years)

3. Use in special circumstances:

• Fosamprenavir unboosted (for children age 2 - 6 years)
• For post-pubertal adolescents who weigh enough to receive adult doses: atazanavir (or indinavir, or saquinavir), each given with low-dose ritonavir boosting, in combination with 2 NRTIs

4. The Working Group does not recommend the following PIs as initial therapy in children either because of insufficient data or data related to toxicity or potency:

• Boosted PIs (with the exception of lopinavir/ritonavir; fosamprenavir with low dose ritonavir in children age >6 years; or for post-pubertal adolescents who can receive adult doses, the combinations of low-dose ritonavir plus atazanavir or indinavir or saquinavir) or full dose dual PIs due to lack of information on appropriate dosing in children
• Atazanavir-containing regimens in children or pre-pubertal adolescents due to lack of pediatric data on appropriate dosage
• Tipranavir- and darunavir-containing regimens due to lack of pediatric data on appropriate dosage and lack of data in antiretroviral naÔve patients
• For adolescents who can receive adult doses, the following dual PI combination should not be given: atazanavir + indinavir (potential for additive hyperbilirubinemia)
• Unboosted saquinavir due to poor oral bioavailability, 3 times daily dosing, and high pill burden
• Nelfinavir is not recommended for initial therapy at the present time due to concerns about the presence a process-related impurity, ethyl methane sulfonate (EMS), in the drug as a by-product of drug manufacture. When this problem is resolved, nelfinavir would be an alternative PI in combination with 2 NRTIs for initial treatment of children >2 years

The above is a selection from the recommendations, the report also includes sections on Selection of Dual NRTI Backbone as Part of Initial Combination Therapy; Coreceptor Tropism Assays; and initial therapies for which there is insufficient data for recommendation for initial therapy for children. As indicated above this more detailed information is available by following the link to the guidelines (1).

References and Links

(1) Havens P, Van Dyke R, Weinberg G and the Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection February 28, 2008. Link to Guidelines: http://aidsinfo.nih.gov/contentfiles/PediatricGuidelines.pdf

(2) World Health Organization (WHO) (2006) Antiretroviral therapy of HIV infection in infants and children: towards universal access. Recommendations for a public health approach Link to source: http://www.who.int/hiv/pub/guidelines/art/en/index.html.

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