Virological Failure

Definition

  • INCOMPLETE SUPPRESSION: HIV-VL > 200 copies/mL at 6 months(i) after starting therapy in PLWH not previously on ART
  • REBOUND: confirmed HIV-VL > 50 copies/mL in PLWH with previously undetectable HIV-VL

General measures

  • Review expected potency of the regimen
  • Evaluate adherence, tolerability, drug-drug interactions, drug-food interactions, psychosocial issues
  • Perform resistance testing on failing therapy (usually routinely available for HIV-VL levels > 200-500 copies/mL and in specialised laboratories for lower levels of viraemia) and obtain historical resistance testing for archived mutations
  • Tropism testing if considering MVC
  • Consider TDM
  • Review ART history
  • Identify treatment options, active and potentially active drugs/combinations

Management of virological failure (VF)

If HIV-VL > 50 and < 200 copies/mL:

  • Check for adherence
  • Check HIV-VL 1 to 2 months later(ii)
  • If genotype not possible, consider changing regimen based on past treatment and resistance history

If HIV-VL confirmed > 200 copies/mL: 

  • Change regimen as soon as possible. What to change will depend on the resistance testing results:
  • If no resistance mutations found: re-check for adherence, perform TDM
  • If resistance mutations found: switch to a suppressive regimen based on drug history; multidisciplinary expert discussion advised
  • Goal of new regimen: HIV-VL < 50 copies/mL within 6 months

Demonstrated resistance mutations

General recommendations:

  • Use at least 2 and preferably 3 active drugs in the new regimen (including active drugs from previously used classes) based on resistance mutations present in current and earlier genotypic analyses
  • Any regimen should use at least 1 fully active PI/b (e.g. DRV/r) plus 1 drug from a class not used previously e.g. INSTI, FI, or CCR5 antagonist (if tropism test shows R5 virus only), or 1 NNRTI (e.g. ETV), assessed by genotypic testing
    • Alternatively, a regimen can be constructed with DTG (when fully active) plus 2 NRTIs, of which at least 1 NRTI is fully active
  • Defer change if < 2 active drugs available, based on resistance data, except in PLWH with low CD4 count (< 100 cells/μL) or with high risk of clinical deterioration for whom the goal is the preservation of immune function through partial reduction of HIV-VL (> 1*log10 reduction) by recycling 
  • If limited options, consider experimental and new drugs, favouring clinical trials (but avoid functional monotherapy). New drugs with promising results include humanised CD4+-binding antibody ibalizumab and attachment inhibitor fostemsavir (currently not licensed by the EMA)
  • Treatment interruption is not recommended. Consider continuation of 3TC or FTC in particular situations even if documented resistance mutation (M184V/I)
  • If many options are available, criteria of preferred choice include: simplicity of the regimen, toxicity risks evaluation, drug-drug interactions, and future salvage therapy

 Footnotes

  1. In PLWH with very high baseline HIV-VL (> 100,000-500,000 copies/mL), achieving viral suppression may take longer than 6 months
  2. In the absence of resistance and in persons fully adherent to treatment, consider non-suppressible viremia due to cellular proliferation [15]

Online video lecture: Adherence and Prevention of HIV Drug Resistance from the EACS online course Clinical Management of HIV