Antiretroviral Therapy Switching Among People with HIV in the United States is not Uncommon Despite Virologic Suppression: An OPERA Cohort Study

Abstract Introduction Although antiretroviral therapy (ART) has substantially improved treatment-related outcomes among people with HIV (PWH), individuals may still undergo ART regimen switches for clinical and non-clinical reasons. While prior studies have focused on virologic outcomes, contemporary data describing ART regimen switching in routine care in the US, especially among virologically suppressed PWH, are limited. In an evolving HIV treatment landscape, including expanding switch strategies, this study estimated the incidence of ART regimen switching among virologically suppressed PWH and characterized switch patterns. Methods This observational cohort study used prospectively collected, routine electronic health records data from the OPERA Cohort. Adult PWH who were active in care and on a complete ART regimen between July 1, 2024 and June 30, 2025 were eligible. An ART regimen switch was defined as any change in antiretroviral agent, excluding pharmacokinetic boosting agents. Incidence of ART regimen switching was assessed during this 1-year period, overall and among PWH who were virologically suppressed. PWH who underwent a switch were characterized. Pre- and post-suppressed switch regimens, as well as patterns of suppressed switching, were outlined. Results Among 73,078 PWH who were eligible, 8188 (11%) experienced ≥ 1 ART regimen switch during the 1-year study period. Of 68,147 individuals who were virologically suppressed to < 200 copies/ml during the study period, 6888 (10%) experienced ≥ 1 ART regimen switch while suppressed. The rate of suppressed switching was 14.5 per 100 person-years. Integrase inhibitors predominated both pre- and post-switch regimens. Overall, 51% of suppressed switches resulted in regimen simplification (lower pill count, fewer anchor agents, and/or transition to a complete long-acting injectable regimen). Conclusions In this large, contemporary US cohort, ART regimen switching was somewhat common and most frequently occurred among virologically suppressed PWH. These real-world findings on the incidence and patterns of virologically suppressed switches provide insight into new trends in treatment optimization and the need for new therapeutic options.