

Jared Leto., left, and Matthew McConaughey in "Dallas Buyers Club." (Focus Features)

'Tis the season for Oscar bait, and this year, "Dallas Buyers Club" looks set to get at least a few nominations. The movie stars Matthew McConaughey as Ron Woodroof, a Dallas man who contracts HIV in 1985, when the diagnosis was a death sentence.

After responding poorly to AZT, the first drug approved to treat HIV/AIDS, Woodroof began acquiring unapproved medications from Mexico, Japan and other places around the world, and formed the titular "buyers club" to distribute them to other people in his area, whether the Food and Drug Administration liked it or not.

It's a very-well-made movie, and McConaughey and Jared Leto (who plays a transgender woman named Rayon who partners with Woodroof) give great performances. And the script, which had been written over the course of 20 years and was based in large part on interviews with Woodroof and on his personal journals, is by all accounts an accurate depiction of Woodroof's life. But it risks leaving a false impression of that period in the history of HIV/AIDS, and in particular of the role of AZT.

Let us now praise AZT



A bottle of AZT, also known by the brand name Retrovir. (Sam Morris / Associated Press)

In 1987, the FDA made azidothymidine — also known as zidovudine and usually shortened to "AZT" — the first government-approved treatment against HIV and AIDS. AZT is an antiretroviral which slows the replication of HIV, although it cannot stop it all together.

In the film, Dallas Mercy Hospital is having a randomized controlled trial to test AZT's effectiveness. Unable to be sure he's getting the drug rather than a placebo in the trial, Woodroof bribes a hospital employee to supply him with AZT, to which he reacts very badly. Throughout the rest of the movie, he and other characters denounce the drug as "toxic," and Woodroof recommends that customers of the buyers club dispose of what AZT they have and never take it again. At one point, a news broadcast is heard which emphasizes that AZT was the most expensive drug ever produced at that point. One could be forgiven for coming away with the sense that the medical community was poisoning HIV/AIDS patients with the drug, and keeping them from other, safer, therapies.

The trouble is that AZT is actually a very effective therapy against HIV/AIDS. "People who were consistently using AZT prolonged life for one year," says Jonathan Engel, a medical historian at Baruch College and author of "The Epidemic: A History of AIDS." That may not sound like a lot, but at a time when the disease had a mortality rate of 100 percent, anything that delayed death was valuable.

This is not to say that Woodruff and others were imagining things. The dosages at which the drug was prescribed really were too high, but that was because of worries that a lower dose wouldn't be enough to meaningfully slow the virus.

Peter Staley, a longtime HIV/AIDS activist and co-founder of the Treatment Action Group who informally consulted on "Dallas Buyers Club," notes that though later studies showed that half the original dose worked just as well, researchers didn’t know this in the early days of the epidemic, and they only figured it out by comparing a lower dose to the original dose and finding the two had same rate of deaths. "They basically had to guess at a dose to use and decided to 'hit hard.'" Staley says. "It was not some government conspiracy that picked a high dose of AZT; it was a fear that hitting the virus too lightly wouldn't do the trick."

That did have negative consequences, notably bone marrow toxicity which manifested as anemia, but those side-effects were easy to diagnose and could be reversed by lowering the dosage or stopping the drug altogether. The bigger problem was that AZT was being used alone. With a virus that mutates as quickly as HIV, using only one antiviral drug often causes the virus to develop a resistance to that therapy. "Even if one half of one percent of cells were resistant, that within 20 generations (or about two months) that could become a broad strain," Engel explains.

The solution, as David Ho and other researchers at the Aaron Diamond AIDS Research Center discovered in the mid-1990s, was to knock the virus back using a "triple whammy" of three different antivirals. Though the odds of a strain developing that was resistant to one of the three antivirals was fairly high, the odds of one developing that was resistant to all three was much lower. This approach — now known as highly active antiretroviral therapy (HAART) — effectively turned HIV/AIDS into a chronic, manageable disease rather than a death sentence.

And AZT, often in the form of a pill marketed as "Combivir" that also included the antiviral lamivudine, was a key component of HAART for almost a decade. "In 2005, the number one selling antiviral in the world was Combivir," Staley says. "This is nine years after the triple drug regimens came out, and well after the AIDS death rate in the developed world dropped by 80 percent between 1996 and 1998. In two years, the death rate collapsed, and combivir was playing a huge role in that."

At Staley's insistence, the film ends with a title-card noting that AZT went on to save millions of lives as part of HAART. But for the other two hours of the film's running time, the drug is spoken about in overwhelmingly negative terms.

What was the alternative?



The real-life Ron Woodroof holding a vial of compound Q. (Randy Eli Grothe / File)

But what of the drugs Woodroof used, and imported, to use in place of AZT? "The stuff he was importing from Mexico was almost all useless," Engel says. A case in point is the experimental drug Peptide T. "[Woodruff] did become a proponent of Peptide T, and he used it himself, and believed it himself," Staley says. "It never panned out. It's a useless therapy, and it never got approved, and nobody uses it today, but the film implies that it helped him."

That and other drugs were what buyers clubs referred to as "what the hell" drugs. They may or may not work, but they weren't likely to do any harm, so why not try them? Woodruff also encouraged buyers club members to take more vitamins, to improve their nutrition, and to quit drinking or abusing illegal drugs — all moves that helped to some extent but not anything that you needed a special buyers club to do. "When you're suffering from any disease, your body's always going to be better with its immune system if you're well-rested and eating well and getting fluids, and that's what he was saying to these people. But it wasn't helping in any way that over the counter didn't," Engel says.

You couldn't say that for all of the drugs Woodroof used and supplied. The original Dallas Life Magazine story upon which the film is based notes that Woodroof supplied herbal remedies like "milk thistle" (which didn't hurt but didn't help either) as well as more serious treatments like compound Q, DDC and alpha interferon.

DDC is an effective antiviral and would go on to be the third drug approved by the FDA to use against HIV/AIDS, but it had harsher side effects than AZT. "It is a sister drug of AZT, and it has its own toxicity profile that is in many respects more dangerous than AZT," Staley said. "In a very small number of patients, it caused nerve damage in the hands and feet that sometimes did not reverse after you stopped the drug. Once better drugs came on the market, it was pulled. It didn't save many lives, and it was the number one thing that Woodroof was selling."

Compound Q, however, backfired, with at least two deaths linked to it over the course of two trials (one FDA-approved, one run "guerrilla-style" by the activist Martin Delaney). "When it became apparent that it could kill people, the FDA tried to get buyers clubs to pull it, and everyone did pull it, except Ron Woodroof," Staley recalls.

This isn't to say that the buyers clubs didn't do any good. As Staley is quick to note, they moved faster than the FDA and the National Institutes of Health (NIH) in using antibiotics and antimicrobials to stop infections enabled by HIV/AIDS's weakening of the immune system.

Don't worry about the government



David Kessler, FDA commissioner from 1990 to 1997, helped speed up drug approvals for HIV/AIDS treatments. (Bloomberg)

Engel and Staley also take issue with the movie's treatment of the FDA, which it portrays as adversarial toward Woodroof and as too slow in responding to AIDS generally. "There's this idea that the FDA, at best, was simply being rigid and democratic and, at worst, were actively homophobic murderers," Engel says. "And this just could not be further from the truth."

The issue is that the FDA was a conservative institution which, because of incidents such as the too-hasty approval of thalidomide (a drug that treated anxiety, nausea and morning sickness but could cause birth defects when used by pregnant women), was traditionally quite cautious about approving new treatments. But it also realized that a laxer approach is called for when dealing with a disease that's 100 percent fatal. The administration started fast-tracking trials for HIV/AIDS treatments, and by 1984 (before Woodroof's diagnosis) the FDA started to loosen the regulatory reins, eventually providing some early access to experimental therapies.

What's more, the FDA was actually fairly cooperative with buyers clubs within a year of their initial formation. "The FDA caved to almost all the demands of AIDS activists and became basically our partner going forward in the 1990s," Staley recalls. "The true story was that we made the system bend, and we used the system and needed the system. I wouldn't be alive today without the companies this film paints as evil, and I wouldn't be alive today without civil servants at the FDA who worked incredibly hard in the 1990s to get these drugs out there quickly."

Woodroof's club did have issues with the FDA, but that was because of his reluctance to stop using harmful treatments like Compound Q. "On these rare occasions the FDA said, 'You're selling something that's killing people,' the Dallas club was the only one that wouldn't cooperate like that and that's what got him in trouble," Staley says. And even when that happened, the dramatic raids portrayed in the film didn't ensue, Staley claims. Woodroof's troubles played out in court, not through big, flashy law enforcement action.

Conclusion



Jennifer Garner and Matthew McConaughey share a laugh on set. (Focus Features)

Overall, Staley and Engel both say they enjoyed the film and that its presence is worthwhile. "It's Hollywood’s first major AIDS film since 'Philadelphia,' so I’m very thankful they’re looking at the issue again, reminding audiences about all the desperation, stigma and courage of the early AIDS years." Staley writes in an e-mail.

But the movie, ultimately, isn't the story of a man who got the treatment he needed despite a government that tried to stop him. It's about a man who tried whatever he could in hopes of extending his life as long as possible, and in the process often rejected helpful treatments and embraced harmful ones. That makes for a less compelling narrative, but it's better history.