Comparative effectiveness and safety of integrase strand transfer inhibitor (INSTI)-based versus non-INSTI-based antiretroviral regimens in treatment-naïve people with HIV: A real-world retrospective cohort study

Integrase strand transfer inhibitor (INSTI)-based regimens are recommended as first-line antiretroviral therapy for HIV-1 infection due to their potent viral suppression and high resistance barrier. However, their long-term effects are not yet fully established, primarily because persistent concerns remain regarding their adverse impacts on metabolic and renal safety in real-world use, coupled with a lack of robust comparative data on their efficacy in treatment-naïve patients with primary drug resistance (PDR), which is a growing clinical challenge. This single-center, retrospective cohort study was conducted at Hangzhou Xixi Hospital, China. We enrolled treatment-naïve people living with human immunodeficiency virus (HIV) initiating antiretroviral therapy between September 2023 and September 2024. According to their initial regimens, the cohort was divided into an INSTI-based group and a non-INSTI-based group. Virological, immunological, metabolic, and renal parameters were assessed at baseline and after 12 months of treatment. Inter-group comparisons of changes from baseline to month 12 were performed using multiple linear regression models, with results expressed as adjusted mean differences. Other statistical analyses included t tests, Mann-Whitney U tests, and chi-square tests, as appropriate. HIV drug resistance mutations were analyzed using sequencing and the Stanford University HIV Drug Resistance Database. This study included 304 treatment-naïve patients, with a median age of 29 years, and male patients accounted for 94.1%. Both regimens achieved high and comparable virological suppression rates and similar CD4 cell recovery. However, the INSTI-based regimen was associated with significantly greater increases in total cholesterol (adjusted mean difference: 0.34 mmol/L, P = .001), triglycerides (0.49 mmol/L, P = .002), and serum creatinine (9.8 μmol/L, P < .001), and a greater decline in estimated glomerular filtration rate (-15 mL/min, P < .001). Among 14 patients with PDR, all 13 receiving an INSTI-based regimen achieved virological suppression, whereas the single patient on a non-INSTI-based regimen experienced virological failure. While demonstrating comparable overall effectiveness at 12 months, INSTI-based regimens were associated with less favorable lipid and renal safety profiles compared with non-INSTI-based regimens. Critically, INSTI-based regimens showed superior efficacy in patients with PDR. In conclusion, our findings support the use of INSTI-based regimens, particularly for patients with PDR, but mandate enhanced monitoring and management of lipid profiles and renal function. Prospective studies with larger sample sizes are warranted to confirm the long-term clinical implications of these findings.