darunavir

TOPLINE:

Among patients with HIV with low-to-moderate cardiovascular risk, both former and current exposure to abacavir was associated with an increased risk for major adverse cardiovascular events (MACE) compared with nonexposure.

METHODOLOGY:

• Researchers conducted a longitudinal secondary analysis of the REPRIEVE trial to examine whether past or current use of antiretroviral therapy (ART) agents was associated with the risk for MACE in patients with HIV.
• The trial enrolled 7769 patients with HIV (median age, 50 years; 68.9% men) who had been on any ART combination for at least 6 months and had low-to-moderate cardiovascular risk and no prior history of cardiovascular disease.
• The median duration of lifetime exposure to ART was 9.6 years; follow-up assessments occurred every 4 months for up to 8 years and 5 months.
• The primary outcome was time-to-first MACE, which is a composite of cardiovascular death, death due to an undetermined cause, myocardial infarction, angina, revascularization, stroke or transient ischemic attack, and peripheral artery disease.
• Secondary outcomes were time-to-first hard MACE defined as cardiovascular death, myocardial infarction, or stroke.

TAKEAWAY:

• Overall, 86.0% of patients were exposed to tenofovir disoproxil fumarate, 49.3% to thymidine analogues, 47.4% to protease inhibitors, and 21.9% to abacavir.
• Exposure to abacavir — both current (hazard ratio [HR], 1.41; 95% CI, 1.01-1.96) and former (HR, 1.62; 95% CI, 1.14-2.30) — was associated with an increased risk for MACE compared with nonexposure even after accounting for potential confounders.
• Neither current nor former exposure to abacavir was associated with the occurrence of hard MACE outcomes compared with nonexposure.
• Although exposure to tenofovir disoproxil fumarate and protease inhibitors was linked to MACE and hard MACE in the unadjusted analyses, these associations were attenuated after adjustment. The exposure to thymidine analogues likewise showed no significant association with any MACE outcomes.

IN PRACTICE:

“Next time, before prescribing abacavir-containing ART, we encourage prescribers to pause, reflect, and discuss with the person in front of them, who is already at greater risk of CVD [cardiovascular disease] than their HIV-negative counterparts, whether this really is the optimal, and ethical, choice,” wrote authors in a commentary.

SOURCE:

The study was led by Carl J. Fichtenbaum, MD, University of Cincinnati College of Medicine, Cincinnati. It was published online on June 4, 2025, in The Lancet HIV.

LIMITATIONS:

This study was limited by potential channeling bias as patients were not randomly assigned to abacavir exposure. Cardiovascular disease events were not evenly distributed. Moreover, the study failed to analyze time-updated longitudinal use of specific ART agents over time.

DISCLOSURES:

This study was supported by the National Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare. Some authors disclosed receiving research grants, personal fees, honoraria, or speaking engagement fees from the study funders as well as other pharmaceutical and healthcare companies. One author reported serving on a data safety monitoring board for a pharmaceutical company outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.