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Integrase inhibitor-based ARV regimen reduces CVD risk in people with HIV

The risk of a serious cardiovascular event is reduced by a fifth in people taking an integrase inhibitor-based antiretroviral regimen compared to alternative drugs. Aidsmap reports that the study by researchers at the Washington University School of Medicine in St Louis, involved over 20,000 people living with HIV who started antiretroviral therapy (ART) for the first time between 2008 and 2015, a quarter of whom took treatment based on an integrase inhibitor.

The researchers’ final analysis showed that, when compared to people taking a regimen based on an alternative drug class, individuals treated with an integrase inhibitor were 21% less likely to experience a serious cardiovascular event such as heart attack or need bypass surgery or a stent.

“We observed a lower risk of cardiovascular disease as measured by major adverse cardiac events, among users of integrase inhibitor-based regimens, after accounting for demographic and clinical characteristics,” comment the researchers.

Cardiovascular disease is now a leading cause of serious illness and death among people with HIV, for several reasons. There is a high prevalence of traditional risk factors (such as smoking) among people with HIV. The inflammation caused by HIV has also been identified as a cause. Individual anti-HIV drugs have also been associated with heightened risk of cardiovascular problems; abacavir can increase the risk of heart attack for reasons that remain uncertain.

However, the relationship between integrase inhibitors and cardiovascular disease is largely unknown.

The report says a group of researchers led by Dr Jane O’Halloran of Washington University therefore designed a study comparing the rates and risk of major cardiovascular events between individuals starting ART according to whether their treatment was based on an integrase inhibitor or an alternative class of antiretrovirals – NNRTIs or protease inhibitors.

Their data source was the medical records of 20,242 people who started ART between early 2008 and late 2015. The information came from private insurance and Medicaid. The study was observational and retrospective – characteristics which mean that its findings cannot be conclusive, a limitation acknowledged by the authors.

Abstract
Background: Several antiretroviral therapy (ART) classes have been associated with increased myocardial infarction (MI) risk. Cardiovascular disease (CVD) in people living with HIV (PLWH) on integrase strand transfer inhibitors (INSTI) has not been examined. Here we aim to examine this.
Setting: Retrospective cohort design study.
Methods: We used the IBM®MarketScan® databases for U.S. commercially insured and Medicaid covered adults to identify PLWH newly initiated on ART between Jan 1, 2008 and Dec 30, 2015. Major adverse cardiac event (MACE), a composite of acute MI, ischemic stroke, coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), was the primary outcome. We used calendar-time specific probability-weighted Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between INSTI use and MACE. We used propensity score weighting methods to account for potential confounding.

Results: 20,242 new ART initiators were identified. 5,069 (25%) PLWH initiated INSTI-based regimens. 203 MACE events occurred; acute MI 16 (0.32%) vs 66 (0.43%), stroke 24 (0.47%) vs 54 (0.36), CABG 2 (0.04%) vs 9 (0.06%), PCI 7 (0.14%) vs 25 (0.16%) of INSTI users vs non-users. INSTI-based ART was associated with significantly lower risk of MACE events (HR 0.79; 95% CI 0.64, 0.96) compared to non-INSTI-based regimens.
Conclusion: In this cohort, INSTI-based regimens were associated with a 21% decreased risk of incident CVD. These finding require validation in other cohorts and with longer follow up.

Authors
O’Halloran, Jane A; Sahrmann, John; Butler, Anne M; Olsen, Margaret A; Powderly, William G

[link url="http://www.aidsmap.com/news/apr-2020/integrase-inhibitors-may-be-associated-lower-risk-cardiovascular-disease-nnrtis-and"]Full Aidsmap report[/link]

[link url="https://journals.lww.com/jaids/Abstract/9000/Integrase_Strand_Transfer_Inhibitors_are.96197.aspx"]Journal of Acquired Immune Deficiency Syndromes abstract[/link]

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