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Another signal of concern with abacavir and cardiovascular risk

In 2008, some researchers reported that the use of abacavir (Ziagen, and in Kivexa, Trizivir and Triumeq) was associated with an increased risk of cardiovascular events (heart attack and so on). However, these reports were based on observational studies that cannot yield definitive results. An analysis of randomized clinical trials by the U.S. Food and Drug Administration (FDA) did not find such an association with abacavir. However, because of the possible cardiovascular risk with abacavir, HIV treatment guidelines usually recommended that it be used cautiously or not at all, particularly in people at high risk for cardiovascular disease. Over the years, use of abacavir has declined significantly, likely because of concern about the drug’s cardiovascular risk.

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A large randomized clinical trial of people with HIV called Reprieve has found that the cholesterol-lowering medicine pitavastatin caused a 36% reduction in the risk of heart attack/stroke, peripheral artery disease and other major cardiovascular events compared to placebo. People were enrolled in Reprieve between 2015 and 2019. At the time of enrollment, their average profile was as follows:

  • age – 50 years
  • 69% male, 31% female
  • 95% cisgender, 2% transgender and 3% did not have a gender recorded by researchers
  • CD4+ count – 621 cells/mm3
  • 88% had an undetectable viral load (thanks to ART)
  • 36% had high blood pressure

Results

Researchers found that 9% of participants had used abacavir in the past, for an average of three years, and 13% were taking it at the time they enrolled in Reprieve. 

Considering many factors—including traditional cardiovascular risks, sex, ethnicity, smoking, high blood pressure, substance use, CD4+ cell count, kidney health and blood sugar levels—researchers found that former and current abacavir users had about a 50% increased risk for heart attack, stroke and other major cardiovascular events. 

This finding is important and reinforces previous data about the cardiovascular risk associated with abacavir. It is concerning because participants enrolled in Reprieve had what researchers called “a low-to-moderate risk” of cardiovascular disease. The findings from Reprieve will likely accelerate the shift away from using abacavir.

—Sean R. Hosein

REFERENCES:

  1. Fichtenbaum CJ, Malvestutto CD, Watanabe MG, et al. Abacavir is associated with elevated risk for cardiovascular events in the REPRIEVE trial. 25th International Conference on AIDS, Munich, Germany, 22-26 July 2024. Abstract OAB3406LB.
  2. Huck DM, Weber B, Parks S, et al. Coronary microcirculatory dysfunction in people with HIV and its association with antiretroviral therapy. Journal of the American Heart Association. 2023 Nov 10;12(22):e029541. 
  3. Yan Q, Huang S, van der Heijden W, et al. Abacavir use is associated with increased prothrombin conversion. Frontiers in Immunology. 2023 Apr 14; 14:1182942.
  4. Guaraldi G, Milic J. Comparing implications of cardiovascular risk of abacavir and integrase inhibitors: why is the scientific community is confused and timid? AIDS. 2023 May 1;37(6):1005-1008. 
  5. Khawaja AA, Taylor KA, Lovell AO, et al. HIV antivirals affect endothelial activation and endothelial-platelet crosstalk. Circulation Research. 2020 Nov 6;127(11):1365-1380. 
  6. Jaschinski N, Greenberg L, Neesgaard B, et al. Recent abacavir use and incident cardiovascular disease in contemporary-treated people with HIV. AIDS. 2023 Mar 1;37(3):467-475.  
  7. Collado-Díaz V, Martinez-Cuesta MÁ, Blanch-Ruiz MA, et al. Abacavir increases purinergic P2X7 receptor activation by ATP: Does a pro-inflammatory synergism underlie its cardiovascular toxicity? Frontiers in Pharmacology. 2021 Mar 31; 12:613449. 
  8. van der Heijden WA, Wan J, Van de Wijer L, et al. Plasmatic coagulation capacity correlates with inflammation and abacavir use during chronic HIV infection. JAIDS. 2021 May 1;87(1):711-719.