Evidence is conflicting about the association of abacavir use and cardiovascular disease (CVD) among HIV-infected individuals. Previous studies may have been biased by the preferential initiation or continuation of ABC in patients with renal dysfunction.

A cohort study was conducted in Kaiser Permanente California during 1998–2011, following HIV-infected adults initiating ART until the earliest of CVD (ie, coronary heart disease or ischemic stroke), health plan disenrollment, death, or end of study. Inverse-probability weighting was used to fit marginal structural models to estimate hazard ratios (HRs) for CVD comparing regimens with and without ABC. Propensity score models included demographics, HIV-specific factors, and CVD risk factors, including alcohol/drug use, smoking, overweight/obesity, diabetes, lipid-lowering and hypertension therapy, and renal dysfunction (ie, estimated glomerular filtration rate <60 mL/min/1.73 m 2 ).

There were small differences between ABC users and nonusers with respect to CVD risk factors at ART initiation, including ever smoking (53% vs. 50%, p = 0.15), alcohol abuse (14% vs. 13%, p = 0.65), drug abuse (17% vs. 18%, p = 0.63), diabetes (4.8% vs. 3.9%, p = 0.22), hypertension medication use (23% vs. 20%, p = 0.045), lipid-lowering therapy use (8.8% vs. 6.2%, p = 0.011), and having a recent eGFR <60 mL/min/1.73 m 2 (7.0% vs. 3.3%, p < 0.001). ABC users were HIV-infected for an average of 2.3 fewer years compared with patients initiating regimens without ABC (3.1 vs. 5.4, p < 0.001), with higher CD4 counts (345 vs. 297 cells per microL, p < 0.001) and lower HIV RNA levels (3.7 vs. 4.1 mean log 10 copies per mL, p < 0.001), but had more ARV experience before initiating combination ART (28% vs. 15%, p < 0.001). ABC initiation decreased over time.

Among 8,154 subjects, 178 had > 1 CVD event, with 24/704 (3.4%) in the ABC group and 154/7,450 (2.1%) in the group initiating regimens without ABC.
In adjusted analyses, ABC was associated with a 2.2-fold higher risk of CVD in intention-to-treat analysis (HR 2.2, 95% CI: 1.4 to 3.5, P = 0.001), a 2.7-fold higher risk in semi-intention- to-treat/per-protocol analysis (remaining on their initial regimens for > 1 year) (HR 2.7, 95% CI: 1.5 to 5.0, P = 0.001), and a non significant 2.1-fold higher risk in per-protocol analysis (HR 2.1, 95% CI: 0.9 to 5.0, P = 0.11). Risk of CVD increased after 3 years of abacavir use.

In conclusion, ABC was associated with an over 2-fold increased risk of CVD, which was not explained by renal dysfunction or other CVD risk factors.