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Background The prevalence of obesity is increasing among people with HIV (PWH), which has significant implications for cardiometabolic health. This study aims to identify which factors are associated with the development of diabetes mellitus (DM) in obese PWH, including the role of antiretroviral treatment (ART), which is still debated in PWH and has never been studied specifically in obese PWH.Methods This was a multicentre, prospective, observational study that enrolled obese PWH in two Italian multicentre cohorts: The Overweight and Obese People with HIV (OBHIV) Cohort and the Surveillance Cohort Long-Term Toxicity Antiretrovirals (SCOLTA) Cohort. Participants were enrolled from 2014 onwards, provided they had at least one follow-up visit and were not diagnosed with DM at enrolment. Factors associated with the onset of DM were estimated using a Cox proportional hazards model. Variables were included in the multivariate model through a forward model selection with p value set at 0.2. We defined low-level viremia as an HIV-RNA value between 50 and 199 copies/mL.Results Three hundred and fourteen obese PWH were enrolled, with a mean BMI of 33.3 kg/m 2 (SD+/-3.7). The mean age was 49 years (SD +/- 11.4) and 70.4% were male. Among study participants, 8% were ART-naïve at enrolment, and 15% were in CDC stage C. Twenty-three developed DM during a mean follow-up of 24 months (IQR 11-38), with an estimated incidence of 3.1/100 PYFU (95%CI 2.0-4.6). Participants with incident diabetes had higher baseline values of blood glucose (p<0.0001), triglycerides (p=0.0003), and ALT (p=0.03) and lower HDL cholesterol (p=0.01). According to the multivariable analysis, incident diabetes was more probable in PWH with higher BMI (aHR 1.11 per each kg/m2, 95%CI 1.003;1.24) and with low-level viremia at the time of DM occurrence, (aHR 4.12, 95%CI 1.5-11.42). Sex and statin use were not correlated to DM incidence in this population, as well as the type of ART (table 1).Conclusions The presence of low-level viremia was strongly associated with the occurrence of DM in this cohort. These results underline a possible interplay between residual inflammation in uncontrolled low-level HIV replication and the risk of diabetes in obese people. No correlation was found between incident DM and exposure to different ART classes.Abstract P154 Table 1Factors associated with incident diabetes obese people with HIV