Down to the Bone: Is an HIV Drug's Link to Fractures Underplayed?

Gilead (GILD)'s HIV drug Viread already carries a warning for loss of bone density, among many others, but a rash of recent studies suggests the FDA should require its much more serious "black box" warning for potential bone fractures. Such a warning could seriously damage sales of Viread, which makes $667 million a year for Gilead and is 10 percent of the company's revenues.

Viread, an anti-retroviral drug, has been on the U.S. market since 2001. Its official prescribing information contains a section warning patients that they may lose "bone mineral density," or BMD, while on the drug. Recently, however, several studies have been published suggesting an alarming link between broken bones and Viread.

One February 2010 study shows that bone fractures are 6.4 times more likely among HIV patients, about 51 percent of whom are on antiretrovirals like Viread. As HIV patients live longer lives, the rate of fractures goes up. In 2008, there were 160 fractures requiring hospitalization for ever 10,000 HIV patients. Among the general population there were only 25 per 10,000. A March 2010 study described how Viread (tenofovir) changes the way genes work, softening bones. And a December 2009 study said there was "a strong correlation" between bone loss and Viread, and described its mechanism. You can see other recent studies linking Viread to bone loss here and here and here and here. They're all from the last two years.

The problem is that none of them specifically measures bone loss with Viread against similar drugs, and against a control population, in a large number of patients. That's the kind of evidence the FDA likes to act upon. So while the evidence suggests there's a link between Viread and bone loss, we don't know how serious it is. (And to be fair to Gilead, HIV is associated with bone loss anyway.)

As the bone-loss issue has only popped up on researchers' radar in the last year or so, many patients and their doctors are unaware that long-term Viread use can leave young-ish men with the bones of 85-year-old women. In a recent column in POZ magazine, AIDS activist Sean Strub describes how he broke his ankle in three places after he stepped off a curb:

Six years ago, when I started Viread, I was told nothing of this possible side effect. While there was already some data indicating some risk, most community clinicians and patient advocates had not been informed about it.

Five friends (all male, in their 40s and 50s) I know who were taking Viread had bone density tests taken, on my recommendation. Four were diagnosed with osteopenia (milder bone loss) and one with osteoporosis.

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