ART: Initiation and Initial Regimen

Initiation of ART in Children and Adolescents

We recommend the initiation of ART in all children and adolescents diagnosed with HIV irrespective of age, clinical stage, CD4 count and VL
We emphasise the need for urgent diagnosis for infants born to women with HIV and urgent initiation of treatment for infants diagnosed with HIV infection, due to their high risk of rapid disease progression
We endorse the “U=U” campaign (undetectable (defined as VL < 200 copies/ml for > 6 months) = untransmissible) for sexual transmission of HIV, which is particularly relevant to sexually active adolescents and is a motivational message to enhance adherence and prevent onward HIV transmission
Although viral suppression markedly reduces transmission, there is no evidence that "U=U" applies to vertical transmission (including transmission through breastfeeding)

Initial Combination Regimen for Children and Adolescents who are ART Naive

See Table 1
Where available, baseline resistance testing should be performed
All first line regimens currently include 2 NRTIs together with a drug from a different class (anchor drug)
DTG plus 2NRTI combination is the preferred option in all children over 4 weeks of age and 3 kg (or BIC plus 2NRTI from 2 years and 14 kg)
Whilst “preferred options” are recommended, “alternative options” are acceptable and remain important choices in settings where availability of ART formulations is limited or for individuals at particular risk of specific toxicity or DDIs
Hepatitis B infection and immunity status should be tested for in all children with HIV and if HBV non-immune vaccination should be completed with subsequent confirmation of immunity. Only children known to be HBV uninfected and HBV immune by surface antibody testing should receive regimens without TDF/TAF. If TDF/TAF not available, alternatives should be discussed within a multidisciplinary team (MDT) or paediatric virtual clinic (PVC)
Whenever possible, first line anchor drugs with a high barrier to resistance should be selected
When choosing a regimen, potential transmitted resistance, including from maternal or infant ART exposure after failed prevention of vertical transmission, should always be considered
Dual therapy as first line is not recommended outside a clinical trial. However, DTG plus 3TC may be considered in individuals from 12 years and 40 kg with HIV-VL < 500,000 copies/ml, documented HBV immunity, and no known or suspected resistance to INSTI or 3TC, following discussion within an MDT or PVC
In infants under 4 weeks and/or under 3 kg, when NVP has been used in pregnancy, or where there is a risk of transmitted NVP resistance, non-NNRTI-based ART, including RAL from birth or LPV/r from 2 weeks are preferred. Once over 4 weeks and 3kg, switching to DTG based ART is recommended as soon as possible to provide a once daily, highly effective, low toxicity, anchor drug with a high barrier to resistance
RAL has a low barrier to resistance. If commenced on RAL under 2 weeks of age and DTG is not available in an appropriate formulation during infancy, then an interim switch to LPV/r to remove the risk of developing INSTI resistance is recommended. Possible challenges with adherence due to poor palatability of LPV/r should be discussed when counselling the parents
In adolescence, with high risk of intermittent adherence, if preferred anchor drugs (BIC or DTG) are not available/appropriate, then DRV/b is favoured due to a higher barrier to resistance compared to EFV, RAL, RPV or DOR

Additional Specific Paediatric Considerations

It should be noted that these Guidelines may include recommendations for use of ARVs outside their European licence. Additionally, in situations where licensed weight cut off is met but minimum age has not yet been reached, possible use should be discussed within an MDT or PVC
Local policy for the use of unlicensed medication in children and adolescents should be followed
Apart from decisions on standard first line ART in high prevalence setting, options should be discussed within an MDT or PVC
If local MDT or PVC are unavailable, an international PVC is accessible by contacting the Guideline Team
Adherence is key to viral suppression and adherence support and assessment should be provided at/prior to initiation of ART and at all subsequent visits
Support from peer mentors, where available, is strongly recommended
Although age cut offs are used in Table 1 it should be noted that weight as well as age are also included in the licensing of ARVs in children
Detailed guidance on paediatric dosing is available from the Penta website
Long acting injectable CAB/RPV is not currently licensed for individuals aged less than 18 years of age in Europe and although it is not yet recommended as an option for children and adolescents, it may be considered on a case by case basis following discussion within an MDT or PVC and following the same general principles as outlined for adults, see Switch Strategies for Virologically Suppressed Persons
TDF/FTC and CAB are licensed in Europe for Pre-exposure Prophylaxis (PrEP) in adolescents over 12 years and over 35 kg. When other agents become approved for use in the adolescent age range, these agents may also be considered. The same principles should be followed as in PreP for adults, see Pre-exposure Prophylaxis (PrEP) with additional prioritisation of safeguarding assessments and social as well as medical support for adolescents at significant risk of acquiring HIV
Recommendations for Post-exposure Prophylaxis (PEP) in adults can be found here. The same general principles apply in children and adolescents. Recommended regimens for adolescent over 12 years and over 35 kg are the same as in adults. Recommended regimens for younger children are available from the Children's HIV Association (Chiva) and can be found here