Cardiovascular risks associated with abacavir and tenofovir exposure in HIV-infected persons

Abstract

Objective: Abacavir use has been associated with cardiovascular risk, but it is unknown whether this association may be partly explained by patients with kidney disease being preferentially treated with abacavir to avoid tenofovir. Our objective was to compare associations of abacavir and tenofovir with cardiovascular risks in HIV-infected veterans.

Design: Cohort study of 10 931 HIV-infected patients initiating antiretroviral therapy in the Veterans Health Administration from 1997 to 2007, using proportional hazards survival regression.

Methods: Primary predictors were exposure to abacavir or tenofovir within the past 6 months, compared with no exposure to these drugs, respectively. Outcomes were time to first atherosclerotic cardiovascular event, defined as coronary, cerebrovascular, or peripheral arterial disease; and time to incident heart failure.

Results: Over 60 588 person-years of observation, there were 501 cardiovascular and 194 heart failure events. Age-standardized event rates among abacavir and tenofovir users were 12.5 versus 8.2 per 1000 person-years for cardiovascular disease, and 3.9 and 3.7 per 1000 person-years for heart failure, respectively. In multivariate-adjusted models, including time-updated measurements of kidney function, recent abacavir use was significantly associated with incident cardiovascular disease [hazard ratio 1.48, 95% confidence interval (CI) 1.08-2.04]; the association was similar but nonsignificant for heart failure (1.45, 0.85-2.47). In contrast, recent tenofovir use was significantly associated with heart failure (1.82, 1.02-3.24), but not with cardiovascular events (0.78, 0.52-1.16).

Conclusion: Recent abacavir exposure was independently associated with increased risk for cardiovascular events. We also observed an association between recent tenofovir exposure and heart failure, which needs to be confirmed in future studies.

Figures

Fig. 1. Cardiovascular disease event rates among users of abacavir, tenofovir, or other antiretroviral therapy (ART)

*P values were less than 0.01, significant compared to use of other antiretroviral therapy.

Fig. 2. Association between recent abacavir exposure and risk of cardiovascular events in subgroups defined by baseline characteristics

CI, confidence interval; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate. CV risk category based on Framingham risk score (20% = high). All estimates based on multivariate adjusted analyses. P value for test of interaction between recent abacavir use and characteristic reported. **Total of 501 events. In three comparisons above (race, CD4 cell count, BMI), there were fewer than 501 events as some participants were categorized under `other race,' or were missing information on CD4 cell count and/or BMI.

Fig. 3. Association between recent tenofovir exposure and risk of heart failure in subgroups defined by baseline characteristics

CI, confidence interval; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate. CV risk category based on Framingham risk score ( 20%= high). All estimates of P value for test interaction between recent tenofovir use and characteristic reported. **Total of 194 events. In three comparisons above (Race, CD4 cell count, BMI), there were fewer than 194 events as some participants were categorized under `other race', or were missing information on CD4 cell count and/or BMI.