Study Reveals Abacavir's Link to Increased Risk of Cardiovascular Events in HIV Patients

A recent secondary analysis of the REPRIEVE trial has uncovered a concerning association between the antiretroviral drug abacavir and an elevated risk of major adverse cardiovascular events (MACE) in patients living with HIV. The study, published in The Lancet HIV on June 4, 2025, highlights the need for healthcare providers to reassess their prescribing practices for this widely used medication.

The REPRIEVE trial, which enrolled 7,769 HIV patients with a median age of 50 years, aimed to evaluate the cardiovascular safety of various antiretroviral therapy (ART) agents. Participants had been on ART for at least six months and had low-to-moderate cardiovascular risk profiles, with no prior history of cardiovascular disease. Over an average follow-up period of 8.5 years, researchers monitored the incidence of MACE, which includes cardiovascular death, myocardial infarction, revascularization, stroke, and peripheral artery disease.

According to Dr. Carl J. Fichtenbaum, lead author and Professor of Medicine at the University of Cincinnati College of Medicine, the findings indicated that both former and current exposure to abacavir was associated with a significantly heightened risk of MACE compared to those who did not take the drug. Specifically, current exposure had a hazard ratio (HR) of 1.41 (95% CI, 1.01-1.96) and former exposure had an HR of 1.62 (95% CI, 1.14-2.30). These results persisted even after adjusting for potential confounders, highlighting the importance of considering cardiovascular health in HIV treatment strategies.

In contrast, exposure to other ART agents like tenofovir disoproxil fumarate and protease inhibitors initially appeared linked to MACE in unadjusted analyses, but these associations diminished after adjustments were made. Interestingly, the study found no significant correlation between abacavir exposure and the occurrence of hard MACE outcomes, which include only cardiovascular death, myocardial infarction, and stroke.

The implications of this study are particularly relevant given the rising prevalence of HIV and the increasing longevity of those living with the virus due to effective ART regimens. Dr. Fichtenbaum emphasized the necessity for prescribers to engage in thorough discussions with patients about the risks and benefits of abacavir, especially considering that individuals with HIV often face a higher baseline risk of cardiovascular disease compared to their HIV-negative peers.

Despite the significant findings, the study is not without limitations. Critics have pointed out potential channeling bias, as patients were not randomly assigned to receive abacavir, and the uneven distribution of cardiovascular events complicates causal interpretations. Moreover, the analysis did not account for time-updated longitudinal use of specific ART agents, which could have provided deeper insights into the evolving risk profiles over time.

The study was supported by various stakeholders, including the National Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare, which raise questions about potential conflicts of interest, given that some authors reported receiving funding and fees from these organizations.

As the HIV treatment landscape continues to evolve, this research underscores the critical need for ongoing vigilance regarding the cardiovascular implications of ART. Future studies should aim to explore the biological mechanisms underlying the increased cardiovascular risk associated with abacavir, as well as the long-term health outcomes of HIV patients on different ART regimens. The findings advocate for a more nuanced approach to HIV management, prioritizing individualized patient care that balances effective viral suppression with the minimization of cardiovascular risks.