Abacavir ART not increasing risk of myocardial infarction or CVD

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Patients who receive abacavir-containing antiretroviral therapy (ART) for HIV do not have an increased risk for myocardial infarction (MI) or coronary artery disease (CAD), according to data presented by researchers from GlaxoSmithKline, UK and ViiV Healthcare, North Carolina, at IDWeek 2017.

Researchers conducted a meta-analysis of 66 clinical trials that focused on the incidence rates (IR) and relative rates (RR) of MI and CAD in patients who were randomly assigned to abacavir-containing ART or other ART or who were prescribed abacavir as background therapy. Shorter duration and non-randomised trials were included in secondary analyses.

A total of 13,119 patients received abacavir-containing ART and 7,350 did not. In patients who received abacavir-containing ART, the MI exposure-adjusted IR was 1.5 per 1,000 person-years (95% CI, 0.67-3.34) vs 2.18 per 1,000 person-years (95% CI, 1.09-4.40) in patients who were not exposed to abacavir-containing ART, with an RR of 0.69 (95% CI, 0.24-1.98). The RR for MI was 0.69 (95% CI, 0.24-1.99) when studies of a shorter duration were included and 0.83 (95% CI, 0.44-1.60) when non-randomised trials were included.

Meanwhile, the IR for CAD in those exposed to abacavir-containing ART was 2.9 per 1,000 person-years (95% CI, 2.09-4.02) vs 4.69 per 1,000 person-years (95% CI, 3.4-6.47) in patients who were not exposed, specifically related to studies with at least 48 weeks of follow-up. With studies that had fewer than 48 weeks of follow-up, the IR for CAD in patients exposed to abacavir was 2.96 per 1000 person-years (95% CI, 2.14-4.08) and 4.6 per 1000 person-years (95% CI, 3.37-6.42) in those who were not exposed to abacavir, with an RR of 0.64 (95% CI, 0.4-1.0).

“These findings provide further evidence against an association between MI and CAD and (abacavir) exposure in this clinical trial population,” the researchers concluded.

“Modifiable risk factors for MI and CAD should be addressed when prescribing ART for treatment of HIV.”

Background: Several observational studies and randomized controlled trials (RCTs) have suggested an association between abacavir (ABC) use and myocardial infarction (MI) but others, including meta-analyses of clinical trial data, have not.
Methods: This updated meta-analysis estimates exposure-adjusted incidence rate (IR) and relative rate (RR) of MI and coronary artery disease (CAD) in subjects receiving ABC and non-ABC-containing combination antiretroviral therapy (cART). Summary data from 52 Phase II-IV RCTs from a previous meta-analysis were combined with aggregate data from 14 new RCTs. Subjects were either randomized to ABC cART vs other cARTs, or ABC was prescribed as a background medication. Primary analyses included ABC-randomized trials with a follow-up of ≥48 weeks and focused on MI. Secondary analyses included shorter duration trials and non-ABC-randomized trials and estimated IR and RR for both MI and CAD.
Results: In 66 clinical trials (75% male, aged 18-85 years), 13,119 adults were on ABC-containing cART and 7,350 were not. Exposure-adjusted IR for MI was 1.5 per 1,000 person-years (PY) [95% Confidence Interval (CI) 0.67 – 3.34] in the ABC-exposed group, and 2.18 per 1,000 PY (95% CI 1.09 – 4.40) in the unexposed group with a RR of 0.69 (95% CI 0.24 – 1.98). RR for MI was 0.69 (95% CI 0.24 – 1.99) with inclusion of shorter duration studies, and 0.83 (95% CI 0.44 – 1.60) with inclusion of ABC non-randomized studies.
The IR for CAD was 2.9 per 1,000 PY (95% CI 2.09- 4.02) in the ABC-exposed group and 4.69 per 1,000 PY (95% CI 3.4- 6.47) in the unexposed group with studies of ≥48 weeks of follow-up, with a RR of 0.62 (95% CI 0.39 -0.98). With inclusion of studies of <48 weeks, IR for CAD in the ABC-exposed group was 2.96 per 1,000 PY (95% CI 2.14-4.08) and 4.65 per 1,000 PY (95% CI 3.37 – 6.42) in the unexposed group with a RR of 0.64 (95% CI 0.4 – 1.0)
Conclusion: This expanded meta-analysis found comparable IRs for MI and CAD among ABC-exposed and unexposed subjects, suggesting no increased risk for MI or CAD following ABC exposure. These findings provide further evidence against an association between MI and CAD and ABC exposure in this clinical trial population. Modifiable risk factors for MI and CAD should be addressed when prescribing ART for treatment of HIV.

Cassandra Nan, Mark S Shaefer, Rimgaile Urbaityte, James Oyee, Judy Hopking, Leigh Ragone, Cynthia McCoig, Vani Vannappagari

Infectious Disease Advisor material ID Week abstract

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