BOSTON — Recent use of the nucleoside analogues abacavir and didanosine is associated with a significantly increased risk of myocardial infarction in HIV-infected individuals, whereas treatment with the thymidine analogues appears to convey no such risk, according to findings presented at the 15th Conference on Retroviruses and Opportunistic Infections.
Using data from the DAD (Data Collection of Adverse Effects of Anti-HIV Drugs) study, a prospective study of more than 33,000 patients from 11 existing cohorts in Europe, Australia, and the United States, Dr. Caroline Sabin of the Royal Free Hospital, London, and her colleagues determined previously that antiretroviral treatment as a whole and protease inhibitor use specifically were associated with an increased risk of cardiovascular disease.
In the current study, 517 myocardial infarctions occurred during the approximately 7 years of follow-up. The study, which looked at the effect of five individual nucleoside reverse transcriptase inhibitors (NRTIs), showed that treatment with abacavir (Ziagen) was associated with a 90% increased risk of MI, and didanosine was associated with a 49% increased risk. Neither of the thymidine analogues—zidovudine or stavudine—nor the nucleoside analogue lamivudine was associated with increased MI risk, Dr. Sabin said. She reported no conflicts of interest pertaining to the study drugs.
The findings were unexpected, she noted, in that the current investigation was undertaken to test the hypothesis that thymidine analogues, because of their known association with dyslipidemia and insulin resistance, might also be associated with an increased risk of heart attack in HIV-infected individuals.
To assess the effect of cumulative, recent (defined as current or within the past 6 months), and past (defined as outside the past 6 months) use of the five NRTIs, the investigators generated Poisson regression models, adjusting for various factors.
Neither cumulative nor recent use of the two thymidine analogues or lamivudine was associated with risk of MI, whereas recent use of abacavir and didanosine predicted risk of MI, Dr. Sabin reported. Additionally, the risks of MI associated with recent abacavir and didanosine use were independent of duration of use and remained after adjustment for HIV-RNA levels, CD4 count, dyslipidemia, and other metabolic factors, she said. Past use of both drugs was not associated with increased risk of MI, which suggests that the unknown biological mechanism for increased MI risk may be reversible upon cessation of the drugs, she added.
To determine the absolute risk of MI among nucleoside analogue users, the investigators incorporated the Framingham predicted 10-year coronary heart disease risk into the main regression model, and determined that the rate of MI was increased by 119% in patients with a moderate 10-year risk and by 222% in patients with a high 10-year risk, relative to those with a low 10-year risk, Dr. Sabin reported. As such, the clinical implications of the findings depend on an individual patient's underlying cardiovascular risk, she said.
The conference was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.