by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer

June 23, 2020

Featured Literature:

O’Halloran, JA. et al. Integrase Strand Transfer Inhibitors are associated with lower risk of incident Cardiovascular Disease in People Living with HIV.
JAIDS March 25, 2020 – Publish Ahead of Print. doi: 10.1097/QAI.0000000000002357

Historically several classes of antiretroviral drugs including protease inhibitors (PI) have been associated with an increased risk of cardiovascular disease (CVD) and myocardial infarction in people living with HIV (PLWH). A similar association with integrase strand transfer inhibitors (INSTI) has not been looked at in observational cohorts such as D:A:D. This retrospective study used the IBM® MarketScan® databases for commercially insured and Medicaid patients to identify those initiated on ART between 2008 and 2015. The primary outcome was “major adverse cardiac event” (MACE) that included a composite of acute MI, ischemic stroke, coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). The authors estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between INSTI and a MACE. Other associations including smoking and use of lipid lowering agents were factored in. During the 8 years of this study, 20,242 patients initiated ART. Twenty-five percent were started on an INSTI, 55% on an Non-NRTI, and 20% on a PI. There was a total of 203 MACE events. These events included acute MI in 16 vs 66 patients, stroke in 24 vs 54, CABG in 2 vs 9, and PCI in 7 vs 25 of INSTI users compared to patients started on a PI or NNRTI-based regimen. Overall Integrase-based ART regimen was associated with a significantly lower risk of a MACE (21% / HR 0.79) compared to non-INSTI-based regimens. For this cohort, INSTI-based regimens were associated with a 21% decreased risk of incident CVD.

Author’s Commentary:

This data was first presented in 2019 at CROI in Seattle and now published. As noted, most of what we know about ART use and CVD risk has come from the D:A:D cohort which identified several PIs and abacavir with an increased risk. This information may be useful for reassuring our patients, although CVD risk in general is complicated and impacted by smoking, lipids, diabetes, and genetics along with other factors. Weight gain with INSTIs has been increasingly reported and this could offset the reduced CDV risk seen in the study. More research from other cohorts along with longer follow-up is definitely needed to clarify and help stratify our patients’ ongoing CVD risk as they age with HIV.

The author has no conflicts of interest to disclose.

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