NEW YORK (Reuters Health) – The nucleoside reverse transcriptase inhibitors (NRTIs) abacavir and didanosine, and the protease inhibitors (PIs) indinavir and lopinavir-ritonavir, all increase the risk of myocardial infarction (MI).

Still, the absolute risk of MI with any particular agent appears to be small, never exceeding 8 cases per 1000 person-years of follow-up, the report indicates.

“We have previously demonstrated an increased risk of MI among patients exposed to combination antiretroviral therapy for longer periods, particularly those exposed to PIs and those recently exposed to NRTIs abacavir and didanosine,” Dr. Signe Westring Worm, from the University of Copenhagen, and co-authors note.

With an additional year of follow-up in the Data Collection on Adverse Events of Anti-HIV Drugs study, the authors were able to assess the risk of MI with 13 anti-HIV agents, including tenofovir, a more recently approved NRTI. Included in the analysis were 33,308 HIV-infected patients.

Each of the agents met prespecified requirements for inclusion in the analysis (at least 30,000 person-years of follow-up with a median individual postexposure follow-up of >1 year). These drugs included: seven NRTIs (zidovudine, stavudine, didanosine, zalcitabine, lamivudine, abacavir, and tenofovir), 4 PIs (indinavir, nelfinavir, lopinavir-ritonavir, and saquinavir), and 2 non-NRTIs (efavirenz and nevirapine).

During 178,835 person-years of follow-up, 580 patients had an MI, according to the report in the Journal of Infectious Diseases for February 1.

Recent exposure to abacavir or didanosine increased the odds of myocardial infarction by 73% and 30%, respectively, after adjusting for latest lipid levels.

Similarly, cumulative exposure to abacavir, indinavir, and lopinavir-ritonavir increased the risk of myocardial infarction by 7%, 8%, and 9% per year, respectively.

By contrast, use of tenofovir, zalcitabine, zidovudine, stavudine, or lamivudine had no significant effect on the risk of myocardial infarction, the authors report.

This study “is one of the largest observational cohorts, representing thousands of individuals living with HIV infection,” Dr. Judith A. Aberg, from New York University School of Medicine, and Dr. Heather Ribaudo, from Harvard School of Public Health, Boston, comment in a related editorial.

The current findings, like the initial report of an association of abacavir with MI, spark controversy, the editorialists note. However, the results will also stimulate “further scientific study to understand the pathogenesis of cardiac risk and interventions to decrease such risk.”

J Infect Dis 2010.