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Background The impact of antiretroviral therapy (ART)-associated weight gain in people with HIV (PWH) who are already obese or overweight still needs to be clarified.Materials and Methods This multicentre, prospective study analysed overweight and obese PWH who were ART-naive in the Italian SCOLTA observational cohort, after they started their first antiretroviral treatment. Weight change was analysed using a linear model adjusted for potentially associated variables.Results A total of 239 people with HIV (PWH) were selected in this study. Of the participants, 198 (82.8%) were overweight and 41 (17.2%) were obese. The mean age was 42.9 years (SD ± 11.7) and 186 (77.8%) were male. The median CD4+T-cell count at enrolment was 370 cells/mm 3 (interquartile range, IQR, 206-514). The study population is further characterized in table 1. During a median follow-up of 24 months (IQR 15-39) the mean weight change observed in this cohort was +0.11 kg/month in overweight individuals (95% CI 0.06; 0.17, p =0.0001) and +0.12 kg/month in obese PWH (95%CI 0.01-0.24, p=0.025). At the multivariate analysis, a significant weight gain, compared to baseline, was shown in people younger than 50 years (+0.16 kg/month, 95%CI 0.03-0.30), of non-Caucasian origin (+0.20 kg/month, 95%CI 0.04-0.35) and in those who were diagnosed with hypertension (+0.20 kg/month, 95%CI 0.04-0.36). However, the change from baseline was not significantly different from that observed their counterparts, namely in people older than 50 years (p=0.39), in Caucasian participants (p=0.09) and in those without hypertension (p=0.08), as detailed in table 2. Regarding risk factor for HIV acquisition, weight gain resulted significant in people who acquired HIV through sexual exposure (+0.08 kg/month, 95%CI 0.11-0.28) or for other/unknown risk factor (+ 0.20 kg/month, 95%CI 0.00-0.38), but not in those who reported intravenous drug use (IVDU), without significant differences among weight trends in the three groups (p= 0.39). In univariate analysis, weight change seemed significant in all the types of ART regimens that were studied, except NNRTI. However, after multivariable adjustment, the weight resulted not significantly different compared to baseline in each of the drug regimens explored, nor resulted different in the inter-group comparisons among regimens. See table 2 for details.Conclusions We observed modest weight changes in overweight and obese PWH who initiated ART, with no influence of different ART classes on the association with weight gain.Abstract OC43 Table 1–2