Emergence of Acquired Dolutegravir Resistance in Treatment-experienced People With Human Immunodeficiency Virus in Lesotho

Abstract

Abstract 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.