Adherence, Virological Failure and Second Line ART

Adherence, Virological Failure and Second Line ART

• Virological failure (defined, see Virological Failure) is almost always due to suboptimal ART adherence, and always requires adherence assessment and support
• Resistance testing is recommended where possible. Choice of second line therapy is dependent on ALL previous ART exposure and documented cumulative HIV resistance mutations at all times tested
• TDM may provide additional useful information, especially in very young children, or in children receiving agents with potential for DDI
• Treatment options in case of virological failure should be discussed within an MDT or PVC, ideally including a virologist

Failed on first line INSTI

• If resistance testing demonstrates no INSTI resistance, consider switch to/ continue INSTI with high barrier to resistance (DTG or BIC) with optimised 2 NRTI
• Switch to PI/b with optimised 2 NRTI is also an option and required if INSTI resistance is demonstrated
• If INSTI resistance and substantial NRTI resistance, consider initial therapy with DTG (bid) + PI/b + optimised 2 NRTI. This should be discussed within an MDT or PVC

Failed on first line PI/b

• If no significant resistance to PIs, consider continuation of PI/b (consider switch to DRV/b) with optimised 2 NRTI
• Consider switch to INSTI with high barrier to resistance (i.e. DTG or BIC)
• Consider INSTI or PI with 2 NRTI single tablet regimen to reduce pill burden (e.g. DRV/c (only in the absence of significant PI resistance), DTG or BIC
• If substantial NRTI resistance consider initial therapy with DTG + PI/b + optimised 2 NRTI. This should be discussed within an MDT or PVC

Failed on first line NNRTI

• Switch to optimised 2 NRTI with either INSTI with a high barrier to resistance (i.e. DTG or BIC) or PI/b
• Consider INSTI or PI with 2 NRTI single tablet regimen to reduce pill burden
• If high VL and substantial NRTI resistance consider using regimen with at least 2 fully active drugs (e.g. INSTI with PI/b and 2 NRTI). This should be discussed within an MDT or PVC

• If resistance testing is available, use results to guide choice of 2 NRTI
• If NRTI resistance is demonstrated, XTC with either TAF or TDF are the preferred options, used according to license and availability of formulations. If TAF or TDF are not available or contraindicated then ZDV can be considered (if not used first line) but alternatives to ZDV including recycling ABC should be discussed if ZDV toxicity is suspected or difficulties with adherence to the twice daily administration are anticipated
• If resistance testing not available, switch to (or continue) TDF or TAF (or ZDV as per above) with XTC (see rationale below)
• TDF or TAF are preferred in second line in combination with XTC (even if failing on TDF or TAF)
• The M184V mutation causes high level resistance to both FTC and 3TC. However ongoing use of either FTC or 3TC is still recommended in the presence of this mutation (especially if it minimises pill burden) as it is associated with an increased viral susceptibility to tenofovir and ZDV

Virological Failure on Second Line Combination

• Virological failure on second line therapy requires further assessment of adherence and resistance testing, even if availability is limited
• TDM may be useful if concerned about subtherapeutic drug levels
• Choice of subsequent regimens should be made through an MDT or PVC, for consideration of request for access to off-label agents
• ART should continue despite virological failure (with a robust INSTI or PI/b based regimen including XTC ) to maintain CD4 count whilst additional adherence support is provided