Cincinnati, OH—An elevated risk of major adverse cardiovascular events (MACE) is linked to the current or previous use of the antiretroviral drug (ARV) abacavir—marketed as Ziagen—according to a presentation at the 2024 International AIDS Conference (AIDS 2024) in Munich, Germany.

The exploratory analysis was from the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), which is primarily funded by the National Institutes of Health (NIH).

University of Cincinnati–led researchers advised that there was no elevated MACE risk for the other antiretroviral drugs included in the analysis.

“Hopefully, with newer antiretrovirals and longer-acting therapy, perhaps this will become less and less of a problem as we're able to shift away and use other things to control HIV replication,” said Carl Fichtenbaum, MD, professor in the division of infectious diseases in the University of Cincinnati (UC) College of Medicine who presented the results.

“Since there are many other options available—certainly in high-income countries—I think we have to consider the fact that the most important thing is controlling HIV replication, but that where we can, it may be helpful to avoid the use of abacavir,” Dr. Fichtenbaum said in a UC press release.

REPRIEVE enrolled 7,769 study participants with HIV from 12 countries and found that daily use of a cholesterol-fighting statin drug reduced the risk of MACE, with the study team also performing statistical analyses to assess whether select ARVs were associated with MACE risk among study participants, all of whom had low-to-moderate CV disease risk.

The authors explained that all ARVs selected for analysis had previously been linked to CV risk and are taken as part of a multidrug ART regimen. Those include:

• Abacavir
• Tenofovir
• Zidovudine
• Stavudine
• Drugs from a class called protease inhibitors (PIs).

Overall, according to the report, 22% of study participants reported prior exposure to abacavir, 86% to tenofovir, 49% to zidovudine or stavudine, and 47% to PIs. At study entry, meanwhile, 13% of participants were taking abacavir, 61% were taking tenofovir, 10% were taking zidovudine or stavudine, and 26% were taking PIs.

The investigators’ analyses determined that participants with prior and current use of abacavir had a 50% and 42% elevated risk of MACE, respectively, compared with participants with no abacavir exposure. Former or current use of other ARVs was not associated with any change in MACE risk, and the coadministration of common ARV drug classes as part of an ART regimen did not appear to impact the elevated MACE risk among participants with current or prior abacavir exposure, the researchers pointed out.

According to the authors, their findings bolster previous studies that also identified an elevated CV disease risk associated with abacavir. The authors called for more research to better understand the increased risk observed in this analysis, including how these findings should be considered in the context of known CV disease risk factors, such as dyslipidemia, diabetes and hypertension, for people with HIV.

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