ART: Preferred & Alternative 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 ZDV(i) + 3TC
ABC(ii) + 3TC		  - LPV/r(iii, iv)
NVP(iv)
RAL(iii)		 RAL(iv)
 4 weeks - 3 years ABC(ii) + 3TC(v)
TAF(vi) + XTC(vii)		 ZDV(i) + 3TC(viii)
TDF(ix) + 3TC		 BIC(x)
DTG(xi)		 LPV/r
NVP
RAL
 3 - 6 years ABC(ii) + 3TC(v)
TAF(vi) + XTC(vii)		 TDF(ix) + XTC
ZDV + XTC		 BIC(x)
DTG(xi)		 DRV/r
EFV
LPV/r
NVP
RAL
 6 - 12 years ABC(ii) + 3TC(v)
TAF(vi) + XTC(vii)		 TDF(ix) + XTC BIC(x)
DTG(xi)

DRV/r
EFV
EVG/c
RAL
 > 12 years ABC(ii) + 3TC(v)
TAF(vi) + XTC(vii)		 TDF(ix) + XTC BIC(x)
DTG(xi)		 DRV/b
EFV(xii)
RAL(xii)
RPV(xii)

Notes

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

  1. 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 at MDT to decide between ZDV or TDF on a case by case basis
  2. ABC should NOT be prescribed to HLA-B*57:01 positive individuals (where screening is available). ABC is not licensed under 3 months of age but dosing data for younger children are available from the WHO and DHHS
  3. 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. In these circumstances the neonate should be monitored closely for LPV/r related toxicity (cardiac, metabolic, endocrine)
  4. 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 (DTG or BIC) is recommended if and when an appropriate licensed formulation is available. If initially commenced on RAL and appropriate DTG or BIC formulations are not predicted to be available in a suitable timeframe then an interim switch to LPV/r could be considered in order to remove risk of developing INSTI resistance while awaiting availability of DTG (or BIC)
  5. At HIV-VL > 100,000 copies/mL ABC + 3TC should not be combined with EFV as anchor drug
  6. TAF is currently licensed in Europe for children 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 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 between 14 kg and 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. When TAF becomes licensed in younger ages and lower weights it should be included as a preferred option. TAF has been associated with excessive weight gain in adults, especially in combination with DTG. This has not yet been demonstrated in paediatric and adolescent observational studies or trials, however the possibility of this should be considered when TAF is used. Families and young people should be counselled regarding this and weight should be monitored. DTG remains the preferred anchor drug due to superior efficacy
  7. XTC indicates circumstances when FTC or 3TC may be used interchangeably
  8. 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
  9. 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
  10. 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 between 14 kg and 25 kg. When BIC becomes licensed in younger ages and weights it can be included as a preferred option
  11. DTG is licensed from 4 weeks and 3 kg. When DTG becomes licensed at younger ages and weights it can be included as a preferred option. Dispersible ABC/3TC/DTG tablets have been recently licensed for children between 14 and 25 kg in Europe. Specific caution should be taken when prescribing dispersible DTG as is not bioequivalent to film coated tablets. DTG has been associated with excessive weight gain in adults, especially in combination with TAF. This has not yet been demonstrated in paediatric and adolescent observational studies or trials, however the possibility of this should be considered when DTG is used. Families and young people should be counselled regarding this and weight should be monitored
  12. Due to predicted poor adherence in adolescence, if preferred anchor drug (BIC or DTG) are not available/appropriate then of the possible alternative anchor drugs, DRV/b is favoured due to a higher barrier to resistance compared to EFV, RAL or RPV