INSTIs and Cardiovascular Risk for HIV Patients

INSTIs have been thought to contribute to weight gain and metabolic syndrome, which in turn may contribute to cardiovascular events in HIV patients.


HIV treatment should not increase the risk for cardiovascular events among patients who are already vulnerable, such as the case with integrase strand-transfer inhibitors (INSTIs), according to a paper published in The Lancet HIV.

Investigators from Denmark used data from an existing large-scale, prospective, observational study in order to determine whether exposure to INSTIs is associated with an increased incidence of cardiovascular disease. It has already been suggested that INSTI use can contribute to weight gain or metabolic syndrome, which in turn can lead to cardiovascular disease, the study authors explained. But INSTIs remain a recommended first-line treatment in North American and European guidelines because of their ability to successfully suppress HIV viral loads, they added.

Among 17 existing European and Australian cohorts, the study authors identified 29,340 HIV-positive individuals with a median age of 44 years, of which 25 percent were female, 74 percent were male and 1 percent were trans. In terms of race and ethnicity, the study authors said 70 percent of participants were white and 10 percent were Black. About half of the patients were exposed to INSTIs during the median 6 years of follow-up and the study authors categorized those patients as:

  • 61 percent were exposed to dolutegravir
  • 24 percent were exposed to cobicistat-boosted elvitegravir
  • 23 percent were exposed to raltegravir
  • 66 percent were exposed to bictegravir

During the follow-up period, the study authors found that 2.5 percent of patients (748 patients) experienced cardiovascular disease, with 299 individuals having myocardial infarctions, 228 having strokes, and 221 having invasive cardiovascular procedures. The study authors determined a crude incidence rate of 4.67 events per 1000 person-years of follow-up.

The crude incidence rate for cardiovascular disease increased from 4.19 events per 1000 person-years of follow-up in patients with no INSTI exposure to a peak incidence of 8.49 events per 1000 person-years of follow-up at more than 0 months to 6 months of INSTI exposure, but then gradually decreased to similar rates among those found with no INSTI exposure after 24 months of no exposure, the study authors wrote.

Interestingly, traditional cardiovascular disease risk factors (smoking, hypertension, dyslipidemia, chronic kidney disease, diabetes) were more prevalent at baseline among those who had a cardiovascular disease event during the follow-up period, the study authors determined. Those individuals who had a cardiovascular disease event tended to be older than those without an event, and their 5-year estimated risk of cardiovascular disease at baseline was consequently higher, the study authors noted.

The investigators did not have the statistical power to look at each cardiovascular event in detail, but noted that the crude incidence rate for myocardial infarctions, strokes, and invasive cardiovascular procedures were consistent with the primary analysis. They were also unable to separate ischemic from hemorrhagic strokes when looking at the 34 of 228 strokes caused by cerebral hemorrhages.

“With cardiovascular disease remaining a common cause of morbidity and mortality among people living with HIV, treatment given to suppress HIV must not add to the cardiovascular risk profile,” the study authors concluded. “Therefore, insights into cardiovascular disease risk factors, including the potential role of individual antiretroviral agents, remain crucial. Our results call for investigations in other large studies and further exploration of potential mechanisms underlying the increased relative cardiovascular risk we found here.”