Abacavir-based ART regimens linked to higher MACE risk in patients with HIV

The risk for major adverse cardiovascular events (MACE) among individuals with HIV infection is higher in those receiving abacavir- vs tenofovir-based antiretroviral therapy (ART), according to results of a study published in Open Forum Infectious Diseases.

Previous research suggests certain ART agents may increase incident MACE among patients with HIV infection, a population known to have higher risk for cardiovascular disease relative to the general public.

Researchers compared the risk for MACE between patients with HIV infection on ART regimens featuring abacavir vs tenofovir backbones. Data for the analysis were sourced from the REPRIEVE study (Clinicaltrials.gov Identifier: NCT02344290), which was designed to assess the effect of statin therapy on MACE risk in patients with HIV at low to moderate risk for cardiovascular disease. Patients (N=6112) were enrolled across 12 countries between 2015 and 2019 and randomly assigned to receive pitavastatin (n=3063) or placebo (n=3049). The primary endpoint was time to first MACE, defined as a composite of cardiovascular death, myocardial infarction, revascularization, and hospitalization for unstable angina, stroke, transient ischemic attack, or peripheral arterial ischemia.

For this analysis, the researchers considered the same primary endpoint across 3 cohorts of patients on different ART backbones, including abacavir (n=307), tenofovir alafenamide (TAF; n=315), and tenofovir disoproxil fumarate (TDF; n=307). To balance for cohort differences, they used an overlap weighting approach.

Among patients in the weighted analysis, 48% to 49% were aged 50 to 59 years, 20% to 22% were women, 43% to 47% reported prior substance use, 36% to 38% had hypertension, and 30% overall reported active smoking. In regard to HIV characteristics, the majority of patients had baseline CD4⁺ counts above 500 cells/mm³ (range, 69%-70%) and reported more than 10 years of ART use (range, 51%-52%).

The researchers noted 62% of the population switched their nucleoside reverse transcriptase inhibitor (NRTI) agent during the follow-up period. Overall, the median time to first switch was 22 months.

Of patients in the abacavir, TAF, and TDF groups, MACE occurred among 5%, 4%, and 2%, respectively. The majority (64%) of MACE were noted prior to NRTI changes.

Between-group analyses indicated higher MACE risk in patients on ART regimens with abacavir (hazard ratio [HR], 2.5; 95% CI, 1.8-3.6) and TAF (HR, 2.0; 95% CI, 1.3-2.9) backbones relative to TDF. The risk for MACE remained higher with abacavir vs TDF backbones after adjustments were made for overlap weighting and censoring at first NRTI switch (adjusted HR, 2.0; 95% CI, 1.2-3.4).

Stratified by MACE outcomes, the risk for myocardial infarction was increased among patients in the abacavir group compared with those in the TDF group (aHR, 3.5; 95% CI, 1.3-9.4).

The researchers observed similar findings in sensitivity analyses restricted to patients in high-income countries and among those who reported use of their entry NRTI agent for less than 1 year.

Study limitations include the lack of data on distinct regimens or interactions with anchor drug class due to small sample sizes, as well as the lack of data on the influence of prior abacavir exposure on MACE risk.

“With the availability of potent and well-tolerated two and three drug ART regimens for both ART-naïve and experienced patients, it is no longer necessary to include ABC [abacavir] in the ART armamentarium,” the researchers noted.

Disclosure: This study was supported by Kowa Pharmaceuticals America, Inc., Gilead Sciences, and ViiV Healthcare. Multiple study authors declared affiliations with industry. Please see the original reference for a full list of disclosures.

By Jessica Nye, PhD

References:

Smith ED, Malvestutto C, Ribaudo HJ, et al. Cardiovascular hazards of abacavir- versus tenofovir-containing antiretroviral therapies: Insights from an analysis of the REPRIEVE trial cohort. Open Forum Infect Dis. Published online March 21, 2025. doi:10.1093/ofid/ofaf177