Background We have previously demonstrated an association betweencombination antiretroviral therapy and the risk of myocardialinfarction. It is not clear whether this association differsaccording to the class of antiretroviral drugs. We conducteda study to investigate the association of cumulative exposureto protease inhibitors and nonnucleoside reverse-transcriptaseinhibitors with the risk of myocardial infarction.
Methods We analyzed data collected through February 2005 fromour prospective observational study of 23,437 patients infectedwith the human immunodeficiency virus. The incidence rates ofmyocardial infarction during the follow-up period were calculated,and the associations between myocardial infarction and exposureto protease inhibitors or nonnucleoside reverse-transcriptaseinhibitors were determined.
Results Three hundred forty-five patients had a myocardial infarctionduring 94,469 person-years of observation. The incidence ofmyocardial infarction increased from 1.53 per 1000 person-yearsin those not exposed to protease inhibitors to 6.01 per 1000person-years in those exposed to protease inhibitors for morethan 6 years. After adjustment for exposure to the other drugclass and established cardiovascular risk factors (excludinglipid levels), the relative rate of myocardial infarction peryear of protease-inhibitor exposure was 1.16 (95% confidenceinterval [CI], 1.10 to 1.23), whereas the relative rate peryear of exposure to nonnucleoside reverse-transcriptase inhibitorswas 1.05 (95% CI, 0.98 to 1.13). Adjustment for serum lipidlevels further reduced the effect of exposure to each drug classto 1.10 (95% CI, 1.04 to 1.18) and 1.00 (95% CI, 0.93 to 1.09),respectively.
Conclusions Increased exposure to protease inhibitors is associatedwith an increased risk of myocardial infarction, which is partlyexplained by dyslipidemia. We found no evidence of such an associationfor nonnucleoside reverse-transcriptase inhibitors; however,the number of person-years of observation for exposure to thisclass of drug was less than that for exposure to protease inhibitors.
Source Information
The members of the writing committee (Nina Friis-Møller, M.D., Ph.D., University of Copenhagen, Copenhagen; Peter Reiss, M.D., Ph.D., Academic Medical Center, Amsterdam; Caroline A. Sabin, Ph.D., Royal Free and University College, London; Rainer Weber, M.D., University Hospital Zurich, Zurich, Switzerland; Antonella d'Arminio Monforte, M.D., D.M.Sc., University of Milan, Milan; Wafaa El-Sadr, M.D., M.P.H., Columbia University, Harlem Hospital, New York; Rodolphe Thiébaut, M.D., Ph.D., INSERM E0338 and U593, Victor Segalen–Bordeaux 2 University, Bordeaux, France; Stephane De Wit, M.D., Ph.D., Centre Hospitalier Universitaire Saint-Pierre, Brussels; Ole Kirk, M.D., D.M.Sc., University of Copenhagen, Copenhagen; Eric Fontas, M.D., Centre Hospitalier Universitaire, Nice, Hôpital de l'Archet, Nice, France; Matthew G. Law, Ph.D., National Centre in HIV Epidemiology and Clinical Research, Sydney; Andrew Phillips, Ph.D., Royal Free and University College, London; and Jens D. Lundgren, M.D., D.M.Sc., University of Copenhagen, Copenhagen) of the DAD Study Group assume responsibility for the overall content and integrity of the article.
Address reprint requests to Dr. Lundgren at the Copenhagen HIV Program, Faculty of Health Sciences, University of Copenhagen, Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark, or at jdl{at}cphiv.dk.
Antiretroviral Drugs and the Risk of Myocardial Infarction
Kaplan R. C., Tien P. C., Lazar J., Zangerle R., Sarcletti M., Pollack T. M., Rind D. M., Sabin C., Friis-Møller N., Lundgren J. D., the Writing Committee of the DAD Study Group , Stein J. H.
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N Engl J Med 2007;
357:715-717, Aug 16, 2007.
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