INTRODUCTION
obesity, atherosclerosis, cardiometabolic complications
OBESITY, CVD, DRUG INTERACTIONS, ATHEROSCLEROSIS, ARTERIAL HYPERTENSION
Integrase strand transfer inhibitors (INSTIs) have become the mainstay of modern antiretroviral treatment (ART). Compared with nonnucleoside reverse transcriptase inhibitors (NNRTIs) or protease inhibitors (PIs), INSTIs have improved virological efficacy, better tolerability, and a lower potential for drug–drug interactions (DDI) [However, concerns about cardiometabolic complications have emerged in recent years. INSTI-based ART is associated with weight increases among treatment-naïve and treatment-experienced individuals [Although arterial hypertension and obesity can contribute to the development of CVD over time, the development of atherosclerosis takes time and is usually not rapidly reversible. Given these pathophysiological mechanisms, the early and transient increase in CVD risk observed in the RESPOND study is unexpected. Because the study analyzed treatment-naïve and treatment-experienced individuals together and applied different inclusion criteria for individuals with and without INSTI-based ART, methodological issues such as confounding by indication, immortal time, and selection bias may have contributed to the findings.The target trial framework helps reduce the potential for bias by specifically aligning the start of follow-up (time 0), eligibility, and the treatment assignment using observational data [