Does switching HIV medication to an integrase inhibitor raise the risk of Major Adverse Cardiovascular Events?
Integrase strand-transfer inhibitors (INSTIs) are a common class of HIV medication. Some studies have linked them to weight gain and metabolic changes. A 2024 study specifically looked at whether switching to an INSTI increases the risk of major adverse cardiovascular events (MACE) — such as heart attack or stroke — in people with HIV who had low-to-moderate cardiovascular risk at the start. The study found a higher risk of MACE after switching to an INSTI compared to staying on a non-INSTI regimen 1.
What the research says
A 2024 retrospective cohort study used data from the global REPRIEVE trial to compare people with HIV who switched to an INSTI versus those who remained on a non-INSTI regimen. The study included 5,114 participants aged 40-75 with low-to-moderate cardiovascular risk. After up to 5 years of follow-up, switching to an INSTI was associated with a higher risk of MACE, as well as increased risks of obesity, diabetes, and hypertension 1. The study accounted for competing events and used weighted Cox models to estimate hazard ratios 1.
Other sources in this set do not directly address INSTIs, but they provide context on MACE risk factors. For example, polypharmacy (taking many medications) and older age were significant predictors of MACE in a rural diabetes cohort 4. Additionally, elevated lipoprotein(a) is a known risk factor for MACE, and its effects may be mediated through inflammatory pathways 2. These findings highlight that multiple factors contribute to cardiovascular risk, and switching HIV medications may add to that risk.
The study on INSTIs specifically focused on people with low-to-moderate baseline risk, meaning the findings may not apply to those with higher baseline risk or different characteristics 1. The authors noted that data on MACE after INSTI switching are scarce, so this study provides important new evidence 1.
What to ask your doctor
- What is my current cardiovascular risk, and how might switching to an integrase inhibitor affect that risk?
- Are there alternative HIV medications that might have a lower risk of metabolic or cardiovascular side effects?
- Should I have my weight, blood sugar, and blood pressure monitored more closely if I switch to an INSTI?
- How does my age and other medications I take influence my overall risk of MACE?
- What signs or symptoms of cardiovascular problems should I watch for after changing my HIV medication?
This question is drawn from common patient questions about Cardiology and answered using cited medical research. We do not provide individualized advice.