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Background In the INSTI-based antiretroviral therapy (ART) era a number of people with HIV (PWH) is still on guidelines (GLs)-outdated or alternative regimens. We aimed to characterize PWH on such regimens and the related features in clinical centers.Methods Cross-sectional analysis in 50 centers of the ICONA cohort including PWH with a last visit in 2024-2025. Regimens were classified as recommended (RecR), outdated (OutR) and alternative (AltR) according to the most recent EACS GLs: OutR were no longer recommended, AltR were considered as alternative to RecR in selected settings (ABC-based regimens, DRV/b+3TC, TDF/F/RPV). Adjusted logistic mixed-effects models including a random intercept for clinical center were used to assess PWH-level and center-level factors associated with use of OutR; center factors were also analyzed for AltR use.Results In total, 10,859 (94.9%) of 11,444 PWH were receiving RecR, 2.7% OutR, and 2.4% AltR. Compared with RecR, PWH on OutR were older [median 57.0 (IQR 47.0–63.0) vs 50.0 (40.0–58.0)], more frequently female (33.0% vs 18.8%), and PWID (15.2% vs 7.7%). PWH on OutR showed a longer treatment-experienced profile, with longer ART exposure [13.1y (8.2-21.2) vs 8.0 (3.1-12.0)], higher prevalence of prior AIDS (18.4% vs 14.4%), and of VF on ART (23.6% vs 9.0%), higher number of ART lines [4 (2-6) vs 3 (1-4)], lower median CD4 count at ART start [290.0 (109.0–446.0) vs 329.0 (164.0–490.0) cells/mm 3] (table 1). Higher median total cholesterol and glucose levels were observed in AltR vs RecR. The detailed breakdown of OutR is shown in figure 1.In the mixed adjusted models, older age (aOR per 10 y 1.14, 95%CI 1.01-1.29) and longer ART duration (aOR per y 1.09, 95%CI 1.07-1.11) and female sex (aOR 1.40, 95%CI 1.04-1.89) were independently associated with OutR use. MSM showed significantly lower odds (aOR 0.66, 95% CI 0.48–0.91), whereas unemployment was associated with an increased risk (aOR 1.50, 95% CI 1.07-2.10). In contrast, higher total cholesterol levels were associated with only a modest increase in odds (aOR per +10 mg/dL: 1.03, 95% CI 1.00-1.06). In the center-level model, neither center size nor HIV care model were associated with OutR and AltR use (table 2). Between-center variation accounted for 19.9% of the variance in use of AltR regimens compared to only 8.0% for OutR, indicating greater standardization across centers in avoiding outdated treatments, but less for AltR.Conclusions OutR use appears primarily driven by patient complexity rather than center organization, supporting the need for targeted ART optimization strategies. Notably, OutR and AltR accounted for 5.1% of cases overall. These findings should be interpreted with caution considering the cross-sectional design, potential survivor bias and limited availability of personal and clinical factors influencing the regimen choice. Therefore, the appropriateness of some prescriptions cannot be excluded.Abstract OC37 Figure 1 and Table 1–2