Real-Life Long-Term Weight Trends After Switching to INSTI-Based Therapy in People Living with HIV: A 12-Year Retrospective Cohort Study

Background: The introduction of integrase strand transfer inhibitors (INSTIs) has transformed HIV therapy, offering high efficacy and tolerability. However, emerging evidence links INSTI exposure to weight gain. The long-term impact of switching from protease inhibitor (PI)–based to INSTI–based combined antiretroviral therapy (cART) on body composition and metabolic health remains incompletely understood. Methods: We conducted a retrospective longitudinal study of 89 virologically suppressed people living with HIV (PLWH) followed from 2008 to 2021. All participants were on PI-based cART at baseline (T₀). Between 2008 and 2013 (T₁), a subset switched to a raltegravir-based INSTI regimen, with subsequent transitions to dolutegravir or bictegravir during follow-up (T₂). Changes in body weight, body mass index (BMI), and metabolic parameters were compared between participants who remained on PI therapy and those who switched to any INSTI (“Ever INSTI”). Results: Over the full observation period, individuals who switched to INSTI-based therapy experienced significantly greater mean increases in body weight and BMI compared with those maintained on PI-based regimens. Immune recovery remained stable across groups, and metabolic safety appeared preserved. Within the INSTI class, participants with prolonged raltegravir exposure exhibited a trend toward greater long-term weight gain, though this finding should be interpreted cautiously due to the small subgroup size and potential residual confounding. Conclusions: Switching from PI- to INSTI-based cART in virologically suppressed PLWH is associated with modest but sustained increases in body weight and BMI over time, without evident deterioration in metabolic health. These results support the favourable safety profile of INSTI-based regimens while underscoring the need for routine anthropometric monitoring and preventive lifestyle interventions during long-term therapy.