Approaches to the Management of Virologic Failure on Dolutegravir-Based Antiretroviral Therapy in the 50 Countries With the Highest Adult Human Immunodeficiency Virus Prevalence

Expanded access to dolutegravir as part of a fixed-dose combination with tenofovir disoproxil fumarate and lamivudine (TLD) has revolutionized global human immunodeficiency virus (HIV) treatment, with more than 25 million people prescribed this regimen in 2024. We reviewed national clinical guidelines for management of virologic failure on first-line TLD in the 50 countries with the highest prevalence of HIV among adults; recent guidelines were not available online for four. Among the remaining 46 country guidelines, we identified four distinct approaches: (1) empiric switch to a protease inhibitor (PI)-based regimen without genotypic resistance testing (GRT) (n = 28; 61%); (2) GRT to guide antiretroviral therapy selection (n = 14; 30%); (3) continuation of TLD without GRT (n = 3; 7%); and (4) empiric switch to a PI-based regimen with concurrent GRT (n = 1; 2%). The diversity of guideline-endorsed approaches underscores the critical need for additional data to inform policy regarding this important clinical scenario.