R263K-associated dolutegravir resistance on tenofovir, lamivudine and dolutegravir: Implications for earlier genotyping and regimen optimisation

Abstract

A South African woman receiving tenofovir, lamivudine and dolutegravir (TLD) with good adherence, developed virological failure with the integrase mutation R263K. Viral suppression was achieved after rapid intensification to dolutegravir 50 mg twice daily combined with atazanavir with ritonavir (ATV/r), with continuation of the nucleoside backbone (dual-anchor regimen). This case highlights the need for earlier resistance testing and specialist-guided salvage therapy for subtype C in resource-limited settings.
Contribution: Archived nucleoside reverse transcriptase inhibitor (NRTI) resistance may render the background drugs functionally inactive, creating functional DTG monotherapy that can select for R263K in HIV-1 subtype C. Swift escalation to salvage therapy may mitigate viraemia. Algorithms should be formulated to warrant earlier genotyping and promote rapid efforts to limit resistance accumulation in patients with documented adherence.