Study Finds Abacavir Increases Cardiovascular Risk in Patients With HIV

Researchers funded by the National Institutes of Health have found that abacavir (Ziagen; ViiV Healthcare) is associated with increased risk of major adverse cardiovascular events (MACE) in patients with HIV. However, it may be mitigated through use of cholesterol-lowering agents, such as statins. The study demonstrated that patients receiving statins experienced 35% fewer MACE compared with those receiving a placebo. These findings suggest a potential for statins to provide an accessible, cost-effective method to reduce cardiovascular disease (CVD) risk and enhance cardiovascular health.

Data indicated that daily use of cholesterol-fighting statin agents offset the high risk of CVD in patients with HIV by 35%. Image Credit: © motortion - stock.adobe.com

The double-blind, phase 3 REPRIEVE trial (NCT02344290)¹ included 2 main analyses: (1) the impact of antiretroviral agents (ARV) on cardiovascular health, and (2) the benefit of statin treatments in patients with HIV. The trial enrolled 7769 patients with HIV from 12 different countries who had to be on any antiretroviral therapy for at least 6 months prior to the study and were considered to have a low-to-moderate risk of CVD, based on the 2013 American College of Cardiology and American Heart Association guideline thresholds. Additionally, there was a median low density lipoprotein (LDL) of 106 mg per dL and the median 10-year atherosclerotic cardiovascular disease risk score was 4.5%. Patients were followed for approximately 5 years before the trial concluded early due to the demonstrated benefits of treatment.^2-4

The study evaluated the impact of several ARVs on CVD risk, including abacavir, tenofovir (Viread; Gilead Sciences), zidovudine (Retrovir; GlaxoSmithKline), and stavudine (Zerit; Bristol-Myers Squibb). Of the participants, 22% reported prior treatment with abacavir, 86% with tenofovir, 49% with zidovudine or stavudine, and 47% with proteasome inhibitors (PI). At enrollment, 13% of participants were taking abacavir, 61% were taking tenofovir, 10% were taking zidovudine or stavudine, and 26% were taking PIs.^2-4

The researchers found that past use of abacavir increased MACE risk by 50% (risk-adjusted HR 1.50, 95% CI 1.04-2.15), while current use increased the risk by 42% (risk-adjusted HR 1.42, 95% CI 1.00-2.00). Additionally, MACE increased in a linear fashion, with a cumulative incidence of 9.74% among former abacavir users and 7.63% in current users at the 96-month follow-up. Similar trends were observed for cardiovascular death, myocardial infarction, and stroke, though these were not statistically significant.^2-4

The researchers also assessed the benefit of pitavastatin (Livalo; Kowa Company, Ltd) on cardiovascular health in patients with HIV. Patients were randomized to receive either 4 mg of pitavastatin or placebo taken orally every day for the duration of the study. Data indicated that daily use of cholesterol-fighting statin agents offset the high risk of CVD in patients with HIV by 35% and prevented 1 in 5 MACE or premature death.^2-4

“Lowering LDL cholesterol levels reduces risks for cardiovascular events, like having a heart attack and stroke, but these findings suggest there may be additional effects of statin therapy that explain these reduced risks among people living with HIV,” said Steven K. Grinspoon, MD, study chair, professor of medicine at Harvard University, and chief of the metabolism unit at Massachusetts General Hospital, in a news release. “Ongoing research about how statin therapy may affect inflammation and increased immune activation among people with HIV may help us better understand the additional benefits we’re seeing with this treatment approach.”²

In response to these findings, the researchers suggest that ARV therapy guidelines should revisit the positioning of abacavir as a first-line treatment. They also recommend discontinuing abacavir due to the evidence of its negative impact on CVD risk in patients with HIV.³

References

1. A Study to Evaluate the Safety and Efficacy of Combination Therapy in Patients With Advanced Cancer. ClinicalTrials.gov. NCT02344290. Updated August 1, 2023. Accessed August 7, 2024. https://clinicaltrials.gov/ct2/show/NCT02344290

2. Daily statin reduces heart disease risk among adults living with HIV. National Institute of Allergy and Infectious Diseases. July 24, 2024. Accessed August 7, 2024. https://www.niaid.nih.gov/news-events/daily-statin-reduces-heart-disease-risk-among-adults-living-hiv

3. Exploratory analysis associates HIV drug abacavir with elevated cardiovascular disease risk in large global trial. News Release. July 23, 2024. Accessed August 7, 2024. https://www.eurekalert.org/news-releases/1052323

4. Antiretroviral abacavir linked with cardiovascular events in REPRIEVE trial. European AIDS Treatment Group. July 29, 2024. Accessed August 7, 2024. https://www.eatg.org/hiv-news/antiretroviral-abacavir-linked-with-cardiovascular-events-in-reprieve-trial/