Antiretroviral Abacavir Linked With Cardiovascular Events in REPRIEVE Trial

Other folks with HIV who took the antiretroviral drug abacavir (Ziagen) had an increased risk of major antagonistic cardiovascular events (MACE), per an exploratory analysis of the REPRIEVE trial.

Previous use of abacavir increased the risk of MACE by 50% (risk-adjusted HR 1.50, 95% CI 1.04-2.15) and present use increased MACE risk by 42% (risk-adjusted HR 1.42, 95% CI 1.00-2.00), reported Carl Fichtenbaum, MD, of the University of Cincinnati, on the International AIDS Conference in Munich.

MACE incidence increased in a linear style over time. At 96 months of note-up, cumulative incidence of MACE amongst former abacavir users became once 9.74% and 7.63% in present users. In contributors who had by no methodology veteran abacavir, the cumulative MACE incidence became once 3.74%.

Of demonstrate, the REPRIEVE trial population became once a “low-to-life like risk neighborhood” for cardiovascular (CV) disease, Fichtenbaum said. The median age of the cohort became once 50. Participants had a median LDL of 106 mg/dL and the median 10-year atherosclerotic CV disease (ASCVD) risk rating became once 4.5%.

Most up-to-date or past use of alternative antiretroviral therapy (ART), in conjunction with protease inhibitors, thymidine analogs, or tenofovir disoproxil fumarate (TDF) became once no longer linked to increased risk of MACE.

In a Q&A session, Agnes Moses, MD, of Partners in Hope in Lilongwe, Malawi, commented, “I’m surely deflated to listen to that it confers the cardiovascular risk, as a result of in general [abacavir] is our slide-to tablets for people with toxicity from TDF.”

“Alternatively, I’m more enthusiastic to discover the mechanisms or pathogenic pathways through which abacavir confers this risk,” she added. Moses became once no longer linked to the gaze.

“We’re very drawn to looking out to discover those mechanisms, as successfully,” Fichtenbaum spoke back. “There would be some endothelial dysfunction. I judge it’d be very attention-grabbing to look at at a few of our genomics and proteomics to survey whether or no longer there are any epigenetic adjustments that admire befell that are long-lasting.”

“Optimistically, with more fresh antiretrovirals and longer-acting therapy, per chance this can change into much less and no longer more of an field as we’re ready to shift away and use other issues to manage HIV replication,” he said.

Abacavir use confirmed identical traits for intriguing MACE events, outlined as CV loss of life, myocardial infarction, and stroke, however became once no longer statistically critical, Fichtenbaum reported.

Fichtenbaum indicated that ART pointers would possibly maybe per chance maybe collected revisit the positioning of abacavir where it is suggested as a major-line agent. “Since there are quite a few other alternatives on hand — absolutely in excessive-income worldwide locations — I judge we favor to sustain in mind the proven truth that the largest thing is controlling HIV replication, however that where we can, it’ll be recommended to book decided of the usage of abacavir,” he said.

In step with a ask from the target market whether there would possibly maybe be a CV income to discontinuing abacavir amongst patients already on the drug, Fichtenbaum spoke back that “the preponderance of proof suggests that stopping it is miles collected a honest recommendation,” whereas furthermore paying attention to modifiable CV risk components.

It has been acknowledged for some time that other folks with HIV are at larger risk for MACE than of us without HIV, even when outdated faculty CV risk components, equivalent to hypertension, ldl cholesterol, and smoking space, are accounted for.

To review a likely intervention for this increased risk, the pivotal REPRIEVE trial looked on the efficacy of the ldl cholesterol-reducing agent pitavastatin (Livalo) in of us with HIV in reducing MACE and came upon that pitavastatin safely lowered incidence of any MACE by 35%.

Amongst the 7,769 contributors enrolled in REPRIEVE, 31% admire been female and 65% admire been non-white. The median CD4 depend became once 621 cells/mm³, and 98% had a viral load underneath 400 copies/mL. Enrolled other folks admire been on precise ART for no longer no longer as much as 180 days.

Of trial contributors, 78% had by no methodology had publicity to abacavir. Of the 22% who had a history of abacavir publicity, 9% had former publicity, with a median length of three years of use. Thirteen percent of contributors admire been at the moment taking abacavir at trial randomization, with a median length of 1.47 years of use. Participants had been taking HIV remedy for a median of 9.5 years and the median length of note-up became once 5.6 years.