CDC Guidelines

The Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection, developed by the HHS Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children, were updated in April 2022.^[1]

Significant changes to guidelines

Two new FDA recommendations have not been fully incorporated into the CDC guidelines yet, but are mentioned below

The FDA has approved long-acting injectable medications cabotegravir� and rilpivirine for use in children and adolescents 12 years and above and weighing at least 35 Kg.�
The FDA has approved abacavir/dolutegravir/lamivudine fixed dose dispersable tablet for children weighing 10 to 25 Kg.�

New recommendations incorporated into CDC guideline

Fixed-dose combination (FDC) bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy) is the preferred initial �integrase strand transfer inhibitor (INSTI) based regimen in children at least 2 years� who weigh at least 14 kg (previously preferred in children older than 6 years who weigh 25 kg or more).
Emtricitabine/tenofavir alafenamide (FTC/TAF)� (Descovy) is recommended as a preferred dual-nucleoside reverse transcriptase inhibitor (NRTI) combination� in children and adolescents weighing at least 14 Kg�when used with an INSTI or non-nucleoside reverse transcriptase inhibitor (NNRTI) (previously recommended for children and adolescents 25 Kg and above).
Doravirine�is a recommended alternative NNRTI, �for �children and adolescents weighing at least 35 Kg, �either in a fixed drug �combination(doravirine/� emtricitabine/ tenofovir disoproxil fumarate� [DOR/FTC/TDF]) or in combination with any 2 non-nucleoside reverse transcriptase inhibitors. This recommendation is based on efficacy and tolerability in adults and pediatric pharmacokinetic studies.
Abacavir (ABC)�: the CDC panel recommends use as preferred� NRTI component �from birth in full-term infants after a negative HLA-B5701 test as part of a dual abacavir/lamivudine (ABC/3TC) or � ABC/FTC combination�(previously ABC/3TC or ABC/FTC was preferred NRTI combination after 3 months of age). This newer recommendation is based on safety data and PK data targeting adult plasma levels.�

When to initiate treatment

Antiretroviral treatment (ART) consisting of 3 drugs from at least 2 classes should be initiated in all treatment-naive infants and children with HIV infection. Delayed treatment for HIV infection is no longer recommended.

Rapid treatment initiation (within 1-2 weeks of diagnosis) is recommended in all HIV-infected children older than 6 weeks but younger than 12 weeks. This rapid initiation must include a discussion concerning the importance of adherence. Some of these infants already will be on treatment as prophylaxis (initiated as soon after birth as feasible in high risk infants), and alteration of this regimen can be considered.

If ART initiation in a child is not possible for any reason, they should be closely monitored virologically (HIV viral load) and immunologically (CD4+ T cells) until treatment is started.

Historically, some older medications had more toxicity and were associated with easier resistance development. Because of this, withholding therapy was once commonly recommended in various age groups and early-stage HIV infection. This no longer is the case, and all children with HIV infection should undergo treatment to avoid disease progression, to avoid infections, to ensure growth and sexual maturation, to avoid neurocognitive consequences of HIV infection, to assist with achieving a normal lifespan, and to eventually avoid further HIV transmission (treatment as prevention).

All children on treatment should be regularly monitored for efficacy of treatment and for any toxicities associated with therapy.

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The following are not to be included in a starting regimen in ARV-Naive children or adolescents:

No 2-drug regimens
No cabotegravir (may be in secondary regimen age 12 and above)
No fostemsavir (no safety data in children and is a salvage medication in adults)
No ibalizumab (monoclonal antibody used as a salvage regimen in adults)

Special considerations when initiating ART in children

Infants and young children require liquid medications or dissolvable powders.�

Toddlers and children require liquid or chewable medication.

These restrictions greatly limit options.

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Therapy in preterm newborns

There are sufficient data on dosing for zidovudine (ZDV)�, lamivudine (3TC)�, and nevirapine (NVP).

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Therapy in term newborns

For term infants, there are also sufficient data on dosing for emtricitabine�, abacavir,� and raltegravir�. Abacavir, although not FDA approved from birth, is recommended by the CDC panel based on PK and safety data to be utilized from birth with the administration held only for HLAB5701 testing (must be HLAB5701 negative to tolerate drug).

For term infants older than 2 weeks (but not preterm infants), there are sufficient dosing data for lopinavir/ritonavir (LPV/r).

Triple therapy should be initiated as soon as diagnosis verified.

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Preferred initial therapy in treatment-naïve infants and children:

Preferred initial therapy in treatment-naïve infants and children consists of a 2–nucleoside reverse transcriptase inhibitor (NRTI) backbone plus an INSTI or nonnucleoside reverse transcriptase inhibitor (NNRTI) (preferred) or PI (alternative and requires boosting).

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NRTI backbone options include the following:

Abacavir plus� lamivudine (3TC)� or emtricitabine (FTC)� preferred after negative HLA-B5701 testing (ZDV substitutes for ABC prior to HLA testing or if tolerated, effective, and preference of family not to switch)
ZDV alternative

Although ZDV is not a preferred ART agent in children older than 6 years, it may be continued rather than changed to another ART agent if it is effectively suppressing the viral load. It also is an alternative choice for initial therapy in children.

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NNRTI options include the following:

For children younger than 14 days, NVP is preferred NNRTI
Rilpivirine alternative therapy for children over the age of 12 years
Efavirenz not recommended under the age of 3 years and not preferred therapy – multiple side effects affecting sleep and causing neuropsychiatric symptoms make this a less desirable choice for children and adolescents

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INSTI options include the following:

Children less than 14 days but ≥2 kg�: Raltegravir (RAL)� (oral suspension or powder for suspension) may be utilized for treatment as prophylaxis in high risk infants�. It is an alternative after 4 weeks of age �when dolutegravirbecomes preferred therapy.
Children at least 4 weeks of age and ≥3 kg: Dolutegravir preferred inital therapy�
Children aged 2 years or older (≥14 kg): Bictegravir (BIC) in fixed dose combination (FDC) a preferred inital therapy
Children aged 3 years or older (≥25 kg):� Elvitegravir/cobicistat�(EVG/c) is an alternative INSTI
Children aged 3 years or older (≥25 kg): Elvitegravir�/cobicistat/emtricitabine/tenofovir alafenamide (EVG/c/FTC/TAF) is a fixed-dose combination option alternative therapy.

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PI options include the following:

Children more than 14 days: Lopinavir/ritonavir (LPV/r) preferred PI therapy
Children more than 3 months�: Atazanavir plus ritonavir (ATV/r) is alternative therapy
Children more than 3 years: Darunavir/r (DRV/r-twice daily)� is alternativetherapy
Cobicistat� (PI booster) and regimens boosted by ritonavir� or cobicistat� may be used as an alternative to ritonavir boosting in children. Atazanavir� boosted with cobicistat� (ATV/c)� is an alternative for children, as is darunavir boosted with cobicistat (DRV/c).