Abstract Body

Introduction

DTG-based regimens have simplified management for providers:

  • Resistance to 1st-line DTG-based regimens is still incredibly rare. Therefore limited role for resistance testing in this scenario; can mostly assume non-adherence if viral load elevated. Fewer resistance tests required; less unnecessary switching drug classes, esp. in LMIC. 
  • “Blind” switching to DTG-based regimens without requiring a resistance test has also been feasible in many cases. This has allowed regimen simplification & better outcomes.

 

Implications for monitoring

  1. More frequent resistance testing will be required.
    1. Will show an example from WHO/SA context of how thinking is changing. 
    2. Cost implications (will show an estimate)
  2. Could baseline InSTI test required if transmitted DR to DTG becomes more prevalent?
    1. Also relevant: problem of ART “initiators” actually being re-initiators, esp. in LMIC. This would further increase the prevalence of “pretreatment” resistance.

 

Implications for management algorithms

  1. In most settings, DTG resistance will necessitate PI (DRV)-based therapy for the foreseeable future, which is:
    1. Not coformulated with full regimen as a single tablet
    2. More expensive
    3. More prone to side effects 
    4. Associated with a worse metabolic profile and more drug-drug interactions
  2. Paradoxical reduction in treatment options compared to situation before 1st line DTG rollout. Previously started with NNRTIs 1st, then had PIs and DTG (3 backbone class options in total), but if starting with InSTI, can really only move to PIs currently (i.e. 2 backbone class options in total) – most NNRTIs don’t do well with concomitant NRTI resistance, unlike PIs/DTG. 
  3. Potential to derail CAB injectable options via cross-resistance: G118R, Q148H/K/R, etc. [BIC almost always cross-resistant also]
  4. Also derails oral dual therapy options: 3TC+DTG, DTG+RPV.
  5. Accelerated need for other options: (doravirine), lenacapavir, islatravir, CAB/RPV, VH-184.
    1. Huge problems with access in many settings though (cost, availability, coformulation, logistics). Not nearly as well studied either. 

 

Conclusion: we’ve been here before! DTG-era was atypical – this is a return to business as usual for HIV community.  Parallels to antimicrobial resistance problems/solutions.