First Line Options, Formulations, Dosing

Table 1. Preferred and Alternative First Line Options in Children and Adolescents

	Backbone		Anchor drug (in alphabetical order)
Age	Preferred	Alternative	Preferred	Alternative
0 - 4 weeks⁽ⁱ⁾	ZDV⁽ⁱⁱ⁾ + 3TC ABC⁽ⁱⁱⁱ⁾ + 3TC	-	LPV/r^{(iv, v)} NVP^{(iv, v, vi)}	RAL^{(v, vii)}
4 weeks - 3 years	ABC⁽ⁱⁱⁱ⁾+ 3TC TAF^(ix)+ XTC^(x)	ZDV⁽ⁱⁱ⁾+ 3TC TDF^(xi)+ 3TC	BIC^(xii) DTG^(xiii)	LPV/r^{(v, vii)} NVP^{(v, vi)} RAL^{(v, vii)}
3 - 6 years	ABC^{(iii, viii)}+ 3TC^(viii) TAF^(ix)+ XTC^(x)	TDF^(xi)+ XTC^(x) ZDV⁽ⁱⁱ⁾+ XTC^(x)	BIC^(xii) DTG^(xiii)	DRV/r^(xiv) EFV^{(viii, xiv)} LPV/r^(xiv) NVP^(xiv) RAL^(xiv)
6 - 12 years	ABC^{(iii, viii)}+ 3TC^(viii) TAF^(ix)+ XTC^(x)	TDF^(xi)+ XTC^(x)	BIC^(xii) DTG^(xiii)	DRV/r^(xiv) EFV^{(viii, xiv)} EVG/c^(xiv) RAL^(xiv)
> 12 years	ABC^{(iii, viii)}+ 3TC^(viii) TAF^(ix)+ XTC^(x)	TDF^(xi)+ XTC^(x)	BIC^(xii) DTG^(xiii)	DRV/b^(xiv) DOR^(xiv) EFV^{(viii, xiv)} RAL^(xiv) RPV^(xiv)

Notes

Toxicities as listed in the table Adverse Effects of ARVs and Drug Classes should be considered. Additional toxicity considerations specific to paediatric patients are described in the footnotes below

These recommendations apply to term infants. Limited data are available to support the use of ZDV, NVP, and 3TC in preterm (gestational age <37 weeks) infants. ABC, LPV/r, and RAL should be avoided in preterm infants, at least during the first 4 weeks of life. Selecting an appropriate ART regimen for this population should be discussed urgently within an MDT or PVC
In view of potential long-term toxicity, any child on ZDV should be switched to ABC or TAF (preferred for younger children) or TDF (alternative for younger children, with renal/bone toxicity monitoring) once increase in age and/or weight makes licensed formulations available. When ABC and TAF are contraindicated or unavailable for young children it is recommended that treatment options are discussed within an MDT or PVC to decide between ZDV or TDF on a case by case basis
Where HLA screening is available, ABC should NOT be prescribed to HLA-B*57:01 positive individuals. ABC is not licensed under 3 months of age but dosing data for younger children are available from the WHO and HHS/NIH
NVP is the preferred option under 14 days of age as LPV/r should not be routinely administered to neonates before a postmenstrual age of 42 weeks and a postnatal age of at least 14 days although it may be considered if there is a risk of transmitted NVP resistance and appropriate INSTI formulations are unavailable. The neonate should be monitored closely for LPV/r related toxicity (cardiac, metabolic, endocrine)
If starting a non-DTG anchor drug in the neonatal period it is acceptable to continue this option. However, when over 4 weeks and 3 kg, a switch to second generation INSTI is recommended if and when an appropriate licensed formulation is available
If using NVP as an anchor drug in children aged 2 weeks to 3 years, consider using 3 NRTI backbone (ABC + ZDV + 3TC) until VL consistently < 50 copies/ml
RAL is an alternative in term neonates under 2 weeks of age if there is a risk of transmitted NVP resistance. However, it has a low barrier to resistance. A switch to an agent with a higher barrier to resistance should be made as early as possible to minimise risk of acquired INSTI resistance. If appropriate DTG or BIC formulations are not available in a suitable timeframe then an interim switch to LPV/r could be considered while awaiting availability of DTG (or BIC)
At HIV-VL > 100,000 copies/ml ABC + 3TC should not be combined with EFV as anchor drug
TAF is currently licensed in Europe for children (from 2 years of age) and adolescents in a number of FDC’s including: TAF/FTC (10/200 mg or 25/200 mg when administered with or without a booster (cobicistat or ritonavir) respectively) from 12 years and 35 kg, TAF/FTC/EVG/c (10/200/150/150 mg) from 2 years and 14 kg, TAF/ FTC/BIC (25/200/50 mg) from 25 kg, TAF/FTC/BIC (15/120/30 mg) from 2 years, and 14 kg to 25 kg, TAF/FTC/DRV/c (10/200/800/150 mg) from 12 years 40 kg, TAF/FTC/RPV (25/200/25 mg) 12 years 35 kg. TAF has been associated with excessive weight gain in adults, especially in combination with DTG. This has not been demonstrated in paediatric and adolescent observational studies or randomised clinical trials, however this possibility should be considered when TAF is used. Families and young people should be counselled, and weight should be monitored
XTC indicates circumstances when FTC or 3TC may be used interchangeably
TDF is only licensed from 2 years of age. In view of concerns about potential impact on bone development and renal toxicity, TAF is recommended over TDF at all ages, in settings where this is licensed and available
BIC is currently licensed in Europe for children and adolescents in the following FDC’s: TAF/FTC/BIC (25/200/50 mg) from 25 kg, TAF/FTC/BIC (15/120/30 mg) from 2 years, and 14 kg to 25 kg. When BIC becomes licensed in younger ages and weights it should be included as a preferred option
DTG is licensed from 4 weeks and 3 kg. When DTG becomes licensed at less than 4 weeks / 3 kg, it should be included as a preferred option. Dispersible ABC/3TC/DTG tablets are licensed for children between 6 and 25 kg in Europe. Note - when prescribing dispersible DTG, it is not bioequivalent to film coated tablets. DTG has been associated with excessive weight gain in adults, especially in combination with TAF (see footnote ix)
If preferred anchor drug (BIC or DTG) are not available/appropriate then of the alternative anchor drugs, DRV/b is favoured due to a higher barrier to resistance