Guidance on the clinical management of HIV-1 persistent low-level viraemia on antiretroviral treatment: a scoping review and an international Delphi consensus

Despite the success of antiretroviral therapy, a subset of people with HIV experience low-level viraemia (LLV), a challenging condition with inconsistent definitions and management across settings. We conducted a scoping review of the literature and developed international consensus recommendations through a modified Delphi process involving a multidisciplinary panel of experts. Available evidence shows wide variability in definitions of persistent LLV, most commonly encompassing repeated viral loads between 50 and 1000 copies per mL. Outcomes associated with LLV are heterogeneous. Despite associations between LLV at 50-200 copies per mL and virological failure of more than 1000 copies per mL, resistance emergence or adverse clinical outcomes are inconsistent; stronger evidence links LLV of 200-1000 copies per mL to these endpoints. Based on these findings, we propose a pragmatic management framework that includes prompt confirmation of LLV, assessment of adherence and drug interactions, consideration of resistance testing (especially at viral loads of 200-1000 copies per mL), a broader clinical evaluation, individualised treatment optimisation (according to viral load strata, the genetic barrier to resistance of current and potential antiretroviral regimens, and the HIV resistance profile), and individual prevention strategies for viral loads of 200-1000 copies per mL. This international guidance aims to support clinicians in identifying when LLV requires action, reduce variability in clinical practice, and inform management strategies across diverse health-care settings.