The risk of MI also remained elevated after cessation of abacavir (Table 2). Further, we found no major difference in estimates between patients who initiated abacavir therapy in the first 2 years after the start of HAART and patients starting abacavir as part of a triple NRTI regimen (Table 2). Almost two-thirds of patients

initiated abacavir therapy 2 or more years after initiation of HAART, a marked difference from use of other NRTIs (Table 3). We conducted a cohort study of all Danish HIV-infected patients treated with HAART to examine the impact of abacavir treatment on risk of a first hospitalization with MI. We confirmed the finding of the DAD study of an increased risk of MI after initiation of abacavir therapy [6]. The major strengths of the study are its nationwide population-based design, combined with long and find protocol nearly complete follow-up. We were Trichostatin A also able to follow the study patients from the time of HAART initiation.

The study has several potential weaknesses that merit discussion. We relied on registry-based discharge diagnoses to identify first-time hospital diagnoses of MI. While discharge diagnoses in general may not be entirely accurate, registration of MI has been shown to be valid [13]. Although we missed patients who died of MI before hospitalization, we assume that rates of pre-hospitalization death are not likely to differ by receipt of abacavir therapy and do not expect potential underreporting of MI-related deaths before hospitalization to bias our relative risk estimates. We also obtained data on comorbidity from the DNHR. This registry includes all in-patient and out-patient hospital contacts in Denmark. As almost all patients with serious diseases are treated in the Danish hospital system, we consider that it is reasonable to assume that this information gives reliable estimates of comorbidity.

We lacked data on certain risk factors for ischemic heart disease, such as serum cholesterol and smoking, but had access to all hospital diagnoses registered in the DNHR and were able tuclazepam to adjust our estimates for several important confounders. We thus expect that our adjusted estimates of relative risk of MI associated with abacavir initiation are robust. Still, some unmeasured or residual confounding may have influenced our risk estimates [14]. It is also important to note that our study cohort was generated in the same era of HAART as the DAD cohort and thus may be subject to the same confounding. Previous reports on the effects of abacavir in observational and randomized studies have been conflicting. Abacavir has been linked to greater risk of lipoatrophy in two observational cohort studies [15,16], but this effect was not confirmed in subsequent randomized trials [17–21].