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
• Second line options should ideally be discussed at a PVC/MDT, ideally including a virologist

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 at MDT/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 where/when licensing allows)
• If substantial NRTI resistance consider initial therapy with DTG + PI/b + optimised 2 NRTI. This should be discussed at MDT/PVC

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 at MDT/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 should be regularly assessed in order to remove from the regimen as soon as possible due to risk of ZDV toxicity over time
• If resistance testing not available, switch to (or continue) TDF or TAF (or ZDV as per above) with 3TC or FTC (see rationale below)
• TDF or TAF are preferred in second line in combination with 3TC or FTC (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

• Subsequent virological failure on second line therapy requires further assessment of adherence and is likely to require 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/PVC
• ART should continue despite virological failure (with a robust INSTI or PI/b based regimen including 3TC or FTC) to maintain CD4 count whilst additional adherence support is provided