Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients.

BACKGROUND: Two nucleos(t)ide reverse transcriptase inhibitors (NRTIs)--abacavir and didanosine--may each be associated with excess risk of myocardial infarction. The reproducibility of this finding in an independent dataset was explored and plausible biological mechanisms were sought. METHODS: Biomarkers, ischemic changes on the electrocardiogram, and rates of various predefined types of cardiovascular disease (CVD) events according to NRTIs used were explored in the Strategies for Management of Anti-Retroviral Therapy (SMART) study. Patients receiving abacavir and not didanosine were compared with those receiving didanosine, and to those receiving NRTIs other than abacavir or didanosine (other NRTIs). Patients randomly assigned to the continuous antiretroviral therapy arm of SMART were included in all analyses (N = 2752); for the study of biomarkers, patients from the antiretroviral therapy interruption arm were also included. RESULTS: Current use of abacavir was associated with an excess risk of CVD compared with other NRTIs. Adjusted hazard ratios for clinical myocardial infarction (n = 19), major CVD (myocardial infarction, stroke, surgery for coronary artery disease, and CVD death; n = 70), expanded CVD (major CVD plus congestive heart failure, peripheral vascular disease, coronary artery disease requiring drug treatment, and unwitnessed deaths; n = 112) were 4.3 [95% confidence interval (CI): 1.4-13.0], 1.8 (1.0-3.1), and 1.9 (1.3-2.9). At baseline in a subset of patients with biomarker data, high sensitivity-C-reactive protein and interleukin-6 were 27% (P = 0.02) and 16% (P = 0.02) higher for patients receiving abacavir (N = 175) compared with those receiving other NRTIs (N = 500). Didanosine was associated neither with altered risk of CVD nor with altered levels of biomarkers. CONCLUSION: Abacavir was associated with an increased risk of CVD. The drug may cause vascular inflammation, which may precipitate a CVD event

Predicting the risk of cardiovascular disease in HIV-infected patients: The Data collection on Adverse Effects of Anti-HIV Drugs Study

Aims: HIV-infected patients receiving combination antiretroviral therapy may experience metabolic complications, potentially increasing their risk of cardiovascular diseases (CVDs). Furthermore, exposures to some antiretroviral drugs seem to be independently associated with increased CVD risk. We aimed to develop cardiovascular risk-assessment models tailored to HIV-infected patients. Methods and results: Prospective multinational cohort study. The data set included 22 625 HIV-infected patients from 20 countries in Europe and Australia who were free of CVD at entry into the Data collection on Adverse Effects of Anti-HIV Drugs Study. Using cross-validation methods, separate models were developed to predict the risk of myocardial infarction, coronary heart disease, and a composite CVD endpoint. Model performance was compared with the Framingham score. The models included age, sex, systolic blood pressure, smoking status, family history of CVD, diabetes, total cholesterol, HDL cholesterol and indinavir, lopinavir/r and abacavir exposure. The models performed well with area under the receiver operator curve statistics of 0.783 (range 0.642–0.820) for myocardial infarction, 0.776 (0.670–0.818) for coronary heart disease and 0.769 (0.695–0.824) for CVD. The models estimated more accurately the outcomes in the subgroups than the Framingham score. Conclusion: Risk equations developed from a population of HIV-infected patients, incorporating routinely collected cardiovascular risk parameters and exposure to individual antiretroviral therapy drugs, might be more useful in estimating CVD risks in HIV-infected persons than conventional risk prediction models