BACKGROUND: Despite advancements in antiretroviral therapy (ART) for people with HIV, barriers to adherence remain, potentially leading to long-term gaps in adherence known as treatment interruptions. These treatment interruptions are associated with viral rebound and can impact the effectiveness of the subsequent regimen and the long-term health of the individual. We aimed to characterize unplanned ART treatment interruptions in the OPERA cohort and investigate virologic outcomes among individuals who resumed treatment with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). METHODS: We identified adults with HIV-1 who were active in care and on an oral ART regimen with ≥ 2 antiretrovirals, including ≥ 1 anchor agent, between 30JUN2021 and 31AUG2023. Individuals with ≥ 1 period of ≥ 45 days without any ART, based on supply from last prescription, were considered to have experienced a treatment interruption. Individuals who resumed treatment by 31AUG2023 were defined as having experienced a treatment interruption with resumption. Each interruption observed during the study period was described, allowing for multiple interruptions per person. Treatment interruptions, pre-interruption regimens, and post-interruption regimens were described. Among individuals who resumed treatment with B/F/TAF, virologic outcomes were investigated through 29FEB2024 using Kaplan-Meier methods. All analyses were repeated with treatment interruption definitions of ≥ 60 and ≥ 90 days. RESULTS: Of 76,883 people for whom a treatment interruption could be observed, 8,550 (11%) experienced ≥ 1 period of ≥ 45 days without any ART. By 31AUG2023, 4,163 (49%) individuals resumed treatment (mean: 1.25 per person) and were included in the study population. The median age was 44 years, 81% were male, 52% Black, 41% White, and 18% Hispanic. Median time since HIV diagnosis was 118 months. B/F/TAF was the most common pre- and post-interruption regimen (49% and 51%, respectively). The cumulative probability of achieving virologic suppression on B/F/TAF was 68% (95% CI: 57, 78) when the viral load measurement was ≥ 200 copies/mL at resumption. CONCLUSIONS: Treatment interruptions occurred in 11% of ART users in routine clinical care during the 26-month study period. Despite treatment interruption increasing the risk for viral rebound, most individuals who resumed treatment with B/F/TAF were able to achieve virologic suppression or avoid virologic failure.