Abstract Background Integrase strand transfer inhibitors (INSTI) have been associated with weight gain, but their effect on short-term overweight/obesity incidence, blood pressure(BP) and metabolic markers change has not been described in treatment-naïve people with HIV(PWH). Methods Medical records of treatment-naïve persons starting ART at the HIV Clinic of University Hospital of Elche(Spain), between January 2007 and July 2019 were retrospectively reviewed. Standard procedures included measurements of weight, BP and metabolic assessment. Data at baseline, 48, 72, and 96 weeks post ART initiation were analysed. We used Cox mixed-effects model to generate predictions of BMI over time and Generalized Additive Mixed Models(GAMM) to relax the linearity assumptions and generate 95% confidence intervals in the multivariable adjust. Results Among 219 (median age 44.0 years, IQR=37.0-53.5; 46 females) participants. Baseline weight mean(SD) was 70.4(13.7)kg without difference between regimens; 66% had a BMI <25 kg/mt2. The incidence of overweight/obesity was significantly greater in persons starting INSTI-based regimens: 15(36.6%) of 41 patients treated with INSTI vs 30(28.9%) of 104 treated with other ART regimens(HR 2.3, 95%CI, 1.2–4.4;p=0.011). In contrast to other ART regimens, patients treated with INSTI showed a significant increase in systolic BP(SBP) (adjusted increase 7.0 mmHg, 95%CI, 0.3–13.7;p=0.039) that was correlated with weight gain (r=0.13, 95%CI, 0.10-0.16;p<0.001). Patients who reached overweight/obesity in INSTI-based ART showed a significant increase in LDL cholesterol. Conclusions INSTI-based ART was associated in the short-term with a greater risk of overweight/obesity and SBP elevation. Patients developing overweight/obesity increased LDL cholesterol with no other metabolic disturbances.