1; oral, Abstract 396]. Abstracts published in Pharmacoepidemiology and D rug Safety, 22(S1):193-194 and available at: Abstract Background: Patients with HIV exposed to the antiretroviral drug abacavir may have an increased risk of cardiovascular disease (CVD). There is concern that this association arises because of a channelling bias. Even if exposure is a risk, it is not clear how that risk changes as exposure cumulates. Methods: We assess the effect of exposure to abacavir on the risk of

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... events in the Swiss HIV Cohort Study. We use a new marginal structural Cox model to estimate the effect of abacavir as a flexible function of past exposures while accounting for risk factors that potentially lie on a causal pathway between exposure to abacavir and CVD. Results: 11,856 patients were followed for a median of 6.6 years; 365 patients had a CVD event (4.6 events per 1000 patient years). In a conventional Cox model, recent -but not cumulative -exposure to abacavir increased the risk of a CVD event. In the new marginal structural Cox model, continued exposure to abacavir during the past four years increased the risk of a CVD event (hazard ratio 2.06, 95% confidence interval 1.43-2.98). The estimated function for the effect of past exposures suggests that exposure during the past 6 to 36 months caused the greatest increase in risk. Conclusions: Abacavir increases the risk of a CVD event: the effect of exposure is not immediate, rather the risk increases as exposure cumulates over the past few years. This gradual increase in risk is not consistent with a rapidly acting mechanism, such as acute inflammation.