Taking an integrase inhibitor as part of an HIV treatment regimen significantly reduced the risk of a major cardiovascular event or coronary artery disease when compared to other forms of HIV treatment, a study in people with HIV in the United States has found.
The study took place in a cohort of people with HIV who may reflect the reality of HIV care in the United States – racially and ethnically diverse with a history of variable access to health care.
The study findings contradict information from studies in other parts of the world which suggest that integrase inhibitor treatment was associated with a raised risk of major cardiovascular disease.
For example, a study of more than 29,000 people with HIV receiving treatment in Europe, Argentina and Australia showed that the risk of a cardiovascular event – a heart attack, a stroke or a clinical intervention to relieve serious heart disease such as stenting or angioplasty – almost doubled in the first six months after starting a regimen containing an integrase inhibitor when compared to other regimens.
But that study also found that after two years, the increased risk for people taking integrase inhibitors had disappeared.
An Italian study of just under 5000 people reported a trend toward a higher risk of cardiovascular events in people who took integrase inhibitors after two years, although the difference was not statistically significant.
However, a study of over 20,000 people in the United States found that starting treatment with an integrase inhibitor was associated with a lower risk of a cardiovascular event than other forms of HIV treatment in people followed for about 18 months. And a study of approximately 5000 people with HIV in Switzerland who were followed for five years found no difference in the risk of heart attack, stroke or clinical intervention to treat heart disease between people who started treatment with an integrase inhibitor or another type of HIV regimen.
Differences between the populations studied as well as the low number of cardiovascular events in some of the studies make it difficult to draw firm conclusions. To investigate further, researchers in the United States looked at a diverse population receiving treatment at centres taking part in the All of Us study, a large, racially diverse cohort.
The study population were taking HIV treatment and did not have any form of cardiovascular disease diagnosed before starting treatment or in the year after starting treatment. The researchers identified a general cohort of 2175 people, comparing cardiovascular risk between those taking integrase or non-integrase inhibitor regimens. They also identified a sub-cohort of 1300 people who started treatment on a non-integrase regimen, comparing those who later switched to an integrase inhibitor with those who did not.
In the general cohort (n=2175), participants were predominantly over 50 (72%), male (68%) and Black or African-American (53%). Approximately 40% were taking lipid-lowering medication and 40% had at least one co-morbidity. Viral load, CD4 count and body mass index measurements were missing for large proportions of participants, probably reflecting variations in access to care.
In the sub-cohort (n=1300), the population characteristics were similar: 78% were aged 50 or over, two-thirds were male, 55% were Black or African-American, 42% were taking lipid-lowering medication and 37% had at least one co-morbidity.
The incidence of cardiovascular events in this cohort study was high: just over one in five participants (21%) experienced either a heart attack, a stroke or was diagnosed with coronary artery disease during the follow-up period, which excluded the first year of treatment in order to rule out the impact of undiagnosed pre-existing serious cardiovascular conditions. However, the high incidence of events in this study is most likely explained by the fact that the investigators chose to count diagnoses of coronary atherosclerosis and angina as events. Both conditions signal that a person has a raised risk of heart attack in the short-to-medium term and may be grounds for clinical intervention. Other studies which have looked at this question have looked only at the incidence of heart attack, stroke or medical procedures to address heart disease.
In the general cohort, two factors were strongly associated with cardiovascular disease. Age over 70 years doubled the risk of a major event or coronary artery disease, while multiple co-morbidities increased the risk threefold. Treatment with an integrase inhibitor was the only demographic or clinical factor associated with a reduced risk of cardiovascular disease. Taking an integrase inhibitor for at least part of an individual’s treatment history was associated with a 64% reduction in the risk of cardiovascular disease, while exclusive treatment with an integrase inhibitor was associated with a 35% risk reduction.
Major risk factors for cardiovascular disease were similar in the sub-cohort. Switching to an integrase inhibitor was associated with a 68% reduction in the risk of cardiovascular disease.
The study investigators say that the reduced risk of cardiovascular events in people taking integrase inhibitors may be attributable to the lack of increases in lipids in people taking these drugs, as well as reductions in lipid levels in people who switch to integrase inhibitors. They also note that compared with most other cohorts studied, the All of US cohort was more racially and ethnically diverse and more likely to capture variations in healthcare access and treatment practices, reflecting the real world of HIV treatment in the United States.
He B et al. Impact of integrase strand transfer inhibitors on cardiovascular disease in people with HIV. Annals of Epidemiology 113: 13-26, 2026 (open access).