Detecting Dolutegravir Resistance: VICONEL-Resistance Project

Dolutegravir (DTG) has become the cornerstone of HIV treatment globally due to its efficacy, tolerability, and comparatively high barrier to resistance. However, emerging DTG resistance—even if still rare—threatens to undermine recent progress in HIV control.

Within VICONEL, we screened for drug resistance among individuals experiencing persistent or recurrent viraemia while taking DTG-based regimens for at least 18 months. In this group, 9% showed intermediate to high-level DTG resistance, raising questions about treatment durability. Similar findings have since been reported in other African settings. In response, the VICONEL-Resistance Project was launched in order to:

  • Identify predictors of DTG resistance to guide early intervention.

  • Assess the effect of genotypic resistance testing (GRT)-informed care on treatment outcomes for people predicted to be at elevated risk for DTG resistance.

  • Quantify the evolutionary accumulation of resistance-associated and compensatory mutations as well as their epidemiological and clinical relevance.

This research is critical to inform management of viraemia with DTG-based ART and to monitor DTG resistance. For settings where GRT is not routinely available, this work will assess ways towards more targeted, risk-informed use of GRT.

Funding:

Swiss National Science Foundation, grant number 10003309

Principal Investigators:

Prof. Niklaus Labhardt

Prof. Roger Kouyos

Project Partners:

Dr. Nadine Tschumi

Dr. Jennifer Brown

Dr. Irene Ayakaka 

Dr. Richard Lessells 

Prof. Niko Beerenwinkel

Prof. Maja Weisser