Adherence, Virological Failure, Second Line ART

Adherence, Virological Failure and Second Line ART

  • Virological failure (defined as 2 consecutive VL > 200 copies/mL at least 3 months apart with adherence support) 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 both on ALL previous ART exposure and documented HIV resistance mutations at all times tested
  • Second line options should ideally be discussed at a PVC/MDT including a virologist, especially if resistance has been found
Choosing a 3rd agent

Failed on first line NNRTI

  • Switch to INSTI with a high barrier to resistance (i.e. DTG or BIC) or PI/b with optimised 2 NRTI
  • If high VL and extensive resistance impacting on NRTIs consider using regimen with at least 2 fully active drugs (e.g. INSTI with PI/b and 2 NRTI)

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 or PI/b based STR to reduce pill burden
  • Consider switch to INSTI with high barrier to resistance (i.e. DTG or BIC)
  • Consider INSTI or PI based single tablet FDC with 2 NRTI to reduce pill burden (e.g. DRV/c (only in the abscense of significant PI resistance), DTG or BIC where/when licensing allows)

Failed on first line INSTI

  • If resistance testing demonstrates no INSTI resistance, consider switch to/continue INSTI with high barrier to resistance with optimised 2 NRTI
  • Switch to PI/b with optimised 2 NRTI is also an option especially if INSTI resistance is demonstrated
  • If INSTI resistance and substantial NRTI resistance, consider initial therapy with DTG (bid) + PI/b + optimised 2 NRTI ideally discussed at MDT/PVC
 Optimizing NRTI backbone
  • If resistance testing 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. If TAF or TDF are not available or contraindicated then ZDV can be considered but alternatives to ZDV should be regularly assessed in order to remove from the regimen as soon as possible
  • If resistance testing not available, switch to (or continue) TDF or TAF (or ZDV as per above) with 3TC or FTC (see below rationale)
  • TDF or TAF are preferred in second line in combination with 3TC or FTC (even if failing on TDF or TAF)
  • It is well established that M184V 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 susceptibility to tenofovir and ZDV

Virological Failure on Second Line Combination

  • Subsequent virological failure on second line therapy requires further assessment of adherence and resistance testing, if available
  • 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 (ideally with a robust INSTI or PI/b based regimen including 3TC or FTC) to maintain CD4 count whilst additional adherence support is provided