Emergence of Acquired Dolutegravir Resistance in Treatment-experienced People With HIV in Lesotho

Background: Since 2019, the World Health Organization has recommended dolutegravir-based antiretroviral therapy (ART) as the preferred regimen for human immunodeficiency virus management. Large-scale programmatic transitioning to dolutegravir-based ART was subsequently implemented across Africa, often in the absence of recent viral load testing and without access to genotypic resistance testing (GRT) in case of viremia. Methods: This study assessed emerging dolutegravir resistance in the routine care of the Viral Load Cohort North-East Lesotho. We included pediatric and adult participants who changed from nonnucleoside reverse transcriptase inhibitor- to dolutegravir-based ART and had at least 1 viral load assessment before and after the change. We sequenced available samples of participants fulfilling the additional virological criteria of having 2 viremic episodes while taking dolutegravir, with at least 1 viral load ≥500 copies/mL taken ≥18 months after changing to dolutegravir. Results: Among 15 349 participants, 157 (1.0%) met the virological criteria, and GRT was successful for 85 (0.6%). Among these 85, 8 (9.4%) had dolutegravir resistance, with 2 (2.4%) and 6 (7.1%) predicted to have intermediate- and high-level dolutegravir resistance, respectively. One participant had 2, 2 had 1, and 5 had 0 active drugs in their regimen. A GRT from before the change to dolutegravir was available for 5 of these 8 participants: 4 had 0 and 1 had 1 active drug in their nonnucleoside transcriptase inhibitor-based regimen. Conclusions: Nine percent of people with persistent or recurring human immunodeficiency virus viremia ≥18 months after changing to dolutegravir-based ART had dolutegravir resistance. Detection and management of emerging dolutegravir resistance must be addressed across Africa.