Abstract
Background: Integrase strand-transfer inhibitors (INSTIs) are linked to weight gain, but data on their cardiometabolic effects, particularly major adverse cardiovascular events (MACE), are scarce. We aimed to estimate the risk of obesity, diabetes, hypertension, and MACE after switching to an INSTI in people with HIV at low-to-moderate cardiovascular risk.
Methods: Using data from the global Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), we emulated a series of trials comparing switching to an INSTI versus remaining on a non-INSTI regimen on risk of incident obesity, diabetes, hypertension, and MACE. Participants without a prior diagnosis of the outcome or prior INSTI use were followed up to five years, until the event, loss to follow-up, death, or study end. Data from emulated trials were pooled and hazard ratios were estimated using weighted Cox-proportional hazard models accounting for competing events.
Findings: 5,114 participants met eligibility criteria for at least one emulated trial. 2,985 (58%) participants were captured as an INSTI switcher in at least one trial. Most switchers (81%) initiated a dolutegravir-based regimen and most (67%) non-switchers were on an efavirenz-based regimen. The average hazard of obesity (HR: 1.41, 95% CI: 1.22-1.59), diabetes (HR: 1.50, 95% CI: 1.24, 1.81), and hypertension (HR: 1.45, 95% CI: 1.26, 1.67) was higher among switchers compared to non-switchers. We did not observe an effect on MACE (HR: 1.17, 95% CI: 0.87-1.57). Point estimates were higher among females compared to males. Results persisted after adjustment for tenofovir alafenamide, tenofovir disoproxil fumarate, prior efavirenz use, and change in BMI.
Interpretation: The increase in cardiometabolic risk profile suggests long-term observation of PWH switching to INSTIs will be critical to ensure appropriate management of co-morbidities and to assess for future development of MACE.