7.2.4 First-line ART for children three years and older (including adolescents)
Consolidated ARV guidelines, June 2013
Rationale and supporting evidence
The United States Food and Drug Administration (172) and European Medicines Agency (173) approved using TDF for children older than two years of age, providing an opportunity to offer the same regimen to both adults and children. Harmonizing treatment recommendations with adult regimens could improve children’s access to ART. Other benefits of TDF include the ability to combine it with 3TC and EFV to create a potent once-daily regimen for children (169). In addition, the fact that HIV resistance to TDF – specifically K65R – can enhance the antiviral effect of AZT may make TDF a good choice for first-line therapy in terms of sequencing NRTIs from first- to second-line regimens (165,174–176). However, experience with TDF in young children is limited, and although TDF is known to reduce bone mineral density, it is not clear whether this is permanent and how it might affect future patterns of growth and fracture risk, as highlighted in the values and preferences survey among health workers. In addition, TDF formulations for younger children are not widely available and to date there are no TDF-containing paediatric fixed-dose combinations.
ABC shares many of the benefits of TDF (once-daily dosage and a favourable resistance profile) but, in contrast to TDF, ABC has been more thoroughly studied in children and is generally well tolerated. ABC is also available in paediatric fixed-dose combination formulations but is significantly more costly. Further, among people with HLA-B*5701, it can cause potentially fatal hypersensitivity; although this is very rare among African children, it can affect up to 3–4% of Caucasian and Asian children (177).
A systematic review based on observational data indicates that EFV has a better shortterm toxicity profile and is associated with better virological response than NVP (121,178). Most children currently receiving ART are treated with regimens that contain NVP, whereas in adults, EFV is increasingly being selected as the preferred NNRTI. The primary reason for this discrepancy relates to the relative availability of NVP or EFV in fixed-dose combinations for children or adults. Children who are well controlled and stable on NVPcontaining regimens do not need to substitute EFV for NVP, but EFV would be a better choice for those initiating ART with other once-daily drugs.
In developing these recommendations, the Guidelines Development Group emphasized:
- using potent first-line regimens;
- the convenience of once-daily dosing and the use of fixed-dose combinations whenever possible;
- using non-thymidine analogues – either ABC or TDF – in first-line regimens to maximize the response to AZT in second-line ART; and
- providing treatment recommendations for older children and adolescents that are aligned with those for adults.