Important note: Information in this article was accurate in 2008. The state of the art may have changed since the publication date.
San Francisco Chronicle - April 2, 2008
Sabin Russell, srussell@sfchronicle.com.
The unexpected finding, which was released at a scientific meeting in February and published online by the journal Lancet on Tuesday, creates a quandary for HIV-positive patients and their physicians. Abacavir has run into trouble just as it was becoming one of the most important "backbones" of various three-drug combinations that keep HIV in check.
"This is a head-scratcher, in the sense that we don't really understand the biology here," said Paul Dalton, director of Treatment and Advocacy for Project Inform in San Francisco.
As a result of the findings, the Food and Drug Administration on Thursday posted a notice that it was reviewing whether to take regulatory action. However, the agency emphasized that it had not concluded that the drug was responsible for the higher heart attack rate, nor was it advising doctors to stop prescribing it.
Abacavir won FDA approval in 1998, and sales of its various formulations have topped $1 billion in recent years. In January, a federal panel that sets treatment guidelines recommended that the drug, combined with the antiviral 3TC and sold as Epzicom, be considered a "preferred choice" for patients taking AIDS drugs for the first time.
Dalton was a member of the Department of Health and Human Services panel that made that recommendation.
Dr. Steven Deeks, a UCSF professor who treats HIV-positive patients at San Francisco General Hospital, said the study was thorough and large-scale, but it is not definitive. It shows a near doubling of heart attack risk, but does not show why.
"The concerns it raises are legitimate," he said.
However, Deeks said that until a plausible biological explanation emerges and the findings are confirmed by other studies, he would be reluctant to recommend that patients who are doing well with abacavir switch to another drug.
Complicating the calculations is that the patients most likely to have heart problems with abacavir are those who already have some underlying medical condition, such as diabetes or high blood pressure, which already puts them at risk. However, the drug regime most clinicians would swap for abacavir uses another highly regarded AIDS medication called tenofovir, which can cause kidney problems - a potential issue for diabetics or people with high blood pressure.
The study, led by researchers at the University of Copenhagen, sifted data from more than 33,000 patients beginning as early as 1999. It found that the risk of heart attack rose nearly 90 percent for those prescribed abacavir.
John Pottage, a vice president for abacavir maker GlaxoSmithKline, said the company is taking the study results very seriously. However, he cautioned that while the risk of heart attack doubled, it was relatively low to begin with - about three per 1,000 patients annually.
After release of the data in February, GlaxoSmithKline revisited 54 clinical trials conducted in the process of winning approval for the medication and found no evidence of heart risk.
"Obviously, the study is provocative, and people are trying to dig into it and understand it," Pottage said.
080402
SC080401
Copyright © 2008 - San Francisco Chronicle Press. All rights reserved. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the San Francisco Chronicle, Permissions Desk, 901 Mission Street, San Franciso, CA 94103. You may also send a fax to (415) 495-3843, or an email message to chronperm@sfgate.com. http://www.sfgate.com.
AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Broadway Cares/Equity Fights AIDS, Elton John AIDS Foundation, the National Library of Medicine, Pacific Life Foundation and donations from users like you.
Always watch for outdated information. This article first appeared in 2008. This material is designed to support, not replace, the relationship that exists between you and your doctor.
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Copyright ©1980, 2008. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .