EACS2023: 475 Below 200: clinical relevance of low-level viremia in participants on ART in the Swiss HIV Cohort Study C. Lanz , T. Loosli , M. Zeeb , M. Stöckle , K. Leuzinger , H. Furrer , J. Laflamme , M. Cavassini , E. Bernasconi , P. Schmid , D.L Braun , R.D Kouyos , K. Kusejko , H.F Günthard , Swiss HIV Cohort Study University Hospital Zurich, University of Zurich, Department of Infectious Diseases and Hospital Epidemiology, Zurich, Switzerland, University Hospital Basel, University of Basel, Division of Infectious Diseases & Hospital Epidemiology, Basel, Switzerland, University Hospital Basel, Department of Clinical Virology, Basel, Switzerland, Bern University Hospital, University of Bern, Department of Infectious Diseases, Bern, Switzerland, University Hospital Geneva, University of Geneva, HIVAIDS Unit, Division of Infectious Diseases, Geneva, Switzerland, University Hospital Lausanne, University of Lausanne, Division of Infectious Diseases, Lausanne, Switzerland, Ente Ospedaliero Cantonale, Division of Infectious Diseases, Lugano, Switzerland, University of Geneva, Geneva, Switzerland, Cantonal Hospital St. Gallen, Division of Infectious Diseases and Hospital Epidemiology, St Gallen, Switzerland General data Abstract category: Antiretroviral therapy – observational studies Abstract body Purpose: The majority of patients treated with contemporary antiretroviral therapy (ART) achieve viral suppression, reflected by HIV plasma viral loads below the limit of detection (<50 copies/mL). However, intermittent episodes of low-level viremia (LLV) occur in a subset of patients, risk factors and clinical significance of which remain debated. Method: We included Swiss HIV Cohort Study (SHCS) participants starting ART between January 2000 and December 2022, with HIV RNA <200 copies/mL six months after starting ART. Using longitudinal information, we applied a time-updated Cox proportional hazards model (update window: 90 days) to determine the association of LLV (50-200 copies/mL) with increased risk of subsequent viral failure, defined as the first measure >200 copies/mL. LLV categories were defined by time-updated area under the curve (AUC) of interpolated HIV RNA values, and divided into low, intermediate and high LLV based on tertiles, and no LLV for AUC being zero. Participants were censored in case of missing HIV RNA values for more than nine months or treatment interruption. Results: Demographic and clinical characteristics of participants with or without LLV differed significantly; the development of LLV was associated with e.g., earlier registration year, heterosexual HIV transmission route, and higher pre-ART HIV RNA (Table). LLV was associated with an increased risk of subsequent viral failure, even after adjustment for demographic and clinical variables ( Figure). The highest category for LLV showed a stronger association (hazard ratio = 3.9) with viral failure than other variables such as ethnicity, age, and ART category (time-updated treatment, channeling bias is likely). All Participants LLV category: No LLV category: Low LLV category: Intermediate LLV category: High P Value (Category "No LLV" versus other LLV categories combined) Total 8137 5801 201 867 1268 Age at registration 38 [31,46] 37 [31,46] 41 [32,49] 38 [31,47] 39 [32,47] <0.001 Registration year 2010 [2005,2015] 2011 [2005,2015] 2009 [2004,2014] 2008 [2003,2012] 2007 [2003,2012] <0.001 Transmission group Men who have sex with men (n, %) 4080 (50.1%) 2966 (72.7%) 90 (2.2%) 414 (10.1%) 610 (15%) 0.018 Heterosexual (n, %) 3061 (37.6%) 2135 (69.7%) 89 (2.9%) 344 (11.2%) 493 (16.1%) People who inject drugs (n, %) 545 (6.7%) 393 (72.1%) 7 (1.3%) 58 (10.6%) 87 (16%) Other or unknown (n, %) 451 (5.5%) 307 (68.1%) 15 (3.3%) 51 (11.3%) 78 (17.3%) Ethnicity White (n, %) 6058 (74.5%) 4314 (71.2%) 140 (2.3%) 652 (10.8%) 952 (15.7%) 0.006 Black (n, %) 1254 (15.4%) 874 (69.7%) 36 (2.9%) 134 (10.7%) 210 (16.7%) Hispanic (n, %) 406 (5%) 318 (78.3%) 9 (2.2%) 36 (8.9%) 43 (10.6%) Asian (n, %) 388 (4.8%) 270 (69.6%) 16 (4.1%) 42 (10.8%) 60 (15.5%) ART start year median, IQR 2010 [2005,2014] 2011 [2006,2015] 2009 [2005,2013] 2008 [2004,2012] 2008 [2004,2011] <0.001 CD4 nadir median, IQR 247 [137,372] 272 [160,404] 173 [61,311] 198 [93.5,307.5] 194 [92.5,292] <0.001 Pre-ART HIV RNA median, IQR 60000 [17193,180260] 45023 [12938,144924] 108000 [40050,307575] 101070 [35325,257000] 112000 [40649,308954] <0.001 (for log RNA) Adherence Missed: Never (n, %) 5434 (66.8%) 3932 (72.4%) 127 (2.3%) 590 (10.9%) 785 (14.4%) <0.001 Missed: 1-2 times per month (n, %) 578 (7.1%) 410 (70.9%) 21 (3.6%) 54 (9.3%) 93 (16.1%) Missed: once per week or more (n, %) 74 (0.9%) 51 (68.9%) 2 (2.7%) 9 (12.2%) 12 (16.2%) Conclusions: In this novel dynamic approach of understanding the impact of LLV over time, we observed that LLV increased the risk for subsequent viral failure, even after adjusting for demographic and clinical characteristics. The detection of LLV should prompt appropriate measures to decrease the risk of subsequent viral failure. General conditions 1. I confirm that I previewed this abstract and that all information is correct. I accept that the content of this abstract cannot be modified or corrected after the submission deadline and I am aware that it will be published exactly as submitted.: Yes 2. I confirm that the submission of the abstract constitutes my consent to publication (e.g. conference website, programmes, other promotions, etc.). : Yes 3. I herewith confirm that the contact details saved in this system are those of the corresponding author, who will be notified about the status of the abstract. The corresponding author is responsible for informing the other authors about the status of the abstract.: Yes 4. 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