AZT is not just a drug; it’s the emblem of a disillusioned culture. Nowadays, when nearly two-thirds of adults born after 1980 are in favor of same-sex marriage, when gays serve openly in the military, when professional sports players identify themselves as gay and it is barely news, it is hard to imagine the stigma attached to sexual orientation and how powerful it remained in the 1980s and even 1990s. In the mid-1990s, when Timothy and Christian were first diagnosed with HIV, a rock musical was premiering in New York City. Rent, a modern take on the classic opera La Bohème, explores the lives of young artists in New York City in the late 1980s as influenced by AIDS. AZT plays its own role in the musical, forcing its users to carry beepers so that they can time their medication precisely. Perhaps even more telling, AZT is effective in the play only for bringing people together, not for treating the virus.
AZT remains a powerful cultural force, symbolic of a dark history. As it entered the public arena, many scientists believed that its arrival would herald an intense celebration. Finally, there was a drug to treat HIV. This did not happen.
AZT was created, screened, and supported by the U.S. government, so it might seem odd that a private company owns the full patent rights to the drug. The fact that a company owns these rights speaks to the desperation of the federal government, which had few partners in developing AIDS drugs and was in no position to contest patent rights. With few companies putting any resources into drugs capable of targeting the burgeoning epidemic, the Food and Drug Administration (FDA) felt it had a responsibility to rush the drug approval process at record speed. This rapid approval took place despite signs in early clinical trials that the drug was considerably toxic.
The first clinical trial of AZT was riddled with both problems and successes. Between February and June 1986, 282 people who were HIV-positive were given either AZT or a placebo. There was a dramatic decrease in mortality in those who received AZT, so dramatic that the regulatory agency couldn’t justify withholding AZT from anyone. The FDA promptly eliminated the placebo in favor of the real thing. Not everyone benefited from the new drug; some patients who took it didn’t experience any benefit. This is because the drug inhibits only one step in the virus’s life cycle. For some viruses, this means drug resistance can build at a rapid pace. The virus mutates quickly, resulting in a viral enzyme that’s able to distinguish between a valid building block and the trick nucleotide that is AZT. The genetics of both the virus and its subsequent mutation rate vary from person to person, and so some patients will develop resistance to the drug more quickly than others. Today, we’re able to accommodate this with myriad drugs, each targeting different parts of the virus and its life cycle. But in the late 1980s, there was only one drug available.
At the same time that researchers were evaluating the effectiveness of AZT in preparation for its approval by the FDA, they were also measuring the toxicity of the drug. Since it was a drug developed for cancer but never used in people, it was difficult to find the right dose that balanced maximum effectiveness with limited toxicity. As AIDS was a deadly disease, most researchers believed it was worthwhile for patients to suffer from some toxicity in order to avoid death. Those measuring toxicity in the AZT collaborative working group in the late 1980s, therefore, reported only their results and gave general guidelines. This group couldn’t recommend a standard dose. Prescribing physicians adjusted the dose up or down on an individual level in response to how well the patient tolerated the drug.
From the first human trial of AZT, it was apparent that the drug had serious side effects. A progressive increase in hemoglobin, the molecule that transports oxygen in the blood, was seen in patients on AZT. At the same time, platelets, which help the blood clot, took a dramatic dip downward. Thirty-one percent of AZT patients needed a red blood cell transfusion, compared to only eleven percent on a placebo. More worrisome was the evidence that the drug was suppressing the bone marrow. The precious stem cells in the bone marrow that eventually develop into the red cells of the blood were suppressed, so newly made red blood cells were suddenly in short supply. Bone marrow suppression is a typical side effect in chemotherapy. It causes headaches, dizziness, and fatigue. AZT became a kind of chemotherapy for HIV. Still, concerns over the toxicity of AZT were, for the most part, pushed aside as the drug entered wide-scale production. The results were published in The New England Journal of Medicine in 1987, four months after AZT’s approval by the FDA. As Broder says, “A consensus on the safety and efficacy of AZT would have been impossible.” After all, people were dying, they needed treatment, and there was no time for expanded safety and dosage testing before the drug was made available.
If there was something worse than the side effects of AZT, it was the price. The drug cost an astounding sum: $10,000 a year. It may not seem so much now, but AZT was the most expensive prescription drug in history. More than the side effects, this number outraged the HIV-positive community. It was hard to believe that a drug that had been developed by a university scientist in the 1960s and screened by government institutes could possibly cost so much. Analysts will explain that the high cost of drugs is needed to motivate companies to take risks and encourage creativity because drug development is an expensive and dangerous enterprise. Inevitably, promising drugs will require heavy investment only to fail. Some will even kill people. However, compared to other drugs developed by pharmaceutical companies, Burroughs Wellcome had made little investment in this drugs’ advancement.
The pricing of AZT stirred both the gay and HIV-positive communities in unprecedented ways. The protests that broke out over AZT were fueled by more than unfair pricing and the drug’s unavailability to those who were desperate for it. They also represented the ire of a community neglected. HIV was a disease that few newspapers wanted to cover, that no politicians wanted to talk about, and that many doctors refused to treat. Thousands of people marched in New York and Washington, DC, and at the Burroughs Wellcome U.S. headquarters in Burlingame, California.
By September 1989, the protests had gained considerable momentum. Seven protestors snuck into the New York Stock Exchange and chained themselves to the VIP balcony, displaying a banner that read SELL WELLCOME. The activists were relentless.
Despite the fact that those with much passion but little experience led the protests, they were enormously successful. Only days after the protest at the stock exchange, Burroughs dropped the price of AZT by several thousand dollars. The drug was still ridiculously expensive, but the fledgling AIDS activists had shown that they had political sway. The feeling of change was intoxicating. Protests over AZT incited the formation of many of the HIV advocacy groups we have today. In 1987, the AIDS Coalition to Unleash Power was formed, dedicated to protesting the tangled story of AZT and the government’s role in it. Today that group, ACT UP, is still a powerful advocate for those with HIV.
The protests influenced more than HIV drug availability. They showed patient advocacy groups everywhere the power of protest. They changed the expectations of patients. No longer were patients content to wait for drugs to be approved. Instead, today they demand access to clinical trials. Patients now know that, with organization and passion, they can make the government fund research into neglected diseases.
Today, expanded and compassionate-use programs are popular for drugs in late-stage clinical trials. Diseases that affect only a small number of people, such as SCID (severe combined immunodeficiency), also known as the boy-in-the-bubble disease, receive considerable research funding. This support has been achieved by grassroots patient advocacy groups that, like the AIDS advocacy groups before them, wield the passion and organization of their members to bring new therapies to market.
The patent for AZT expired in 1995. Anyone can now make or sell it. Jerome Horwitz, the original inventor of the clever drug that tricks DNA, never shared in the enormous profits. In 1992, Burroughs Wellcome, today GlaxoSmithKline, reported sales of $400 million. AZT is still used today, typically as the first line of defense in protecting infants from contracting HIV from their mothers. When combined with other antiretroviral drugs and given in much lower doses than those in the late 1980s, the drug is effective against HIV.
For researchers, AZT represents the first success in the fight to cure AIDS. It defeated what Sam Broder termed “therapeutic nihilism.” Meaning it showed what many scientists simply didn’t believe was possible: We can treat a retrovirus. It was an era when successful treatment for any virus was novel. The breakthrough research that gave us AZT is the basis for all the HIV drugs we have today. Robert Gallo, the American scientist who shared in the discovery that HIV causes AIDS, believes that AZT opened a new “window of opportunity” for the way we treat the disease, saying that the drug spurred him to focus on the human cell and its machinery when looking for new drug targets. Similarly, Broder believes that the advent of AZT changed the “cure or nothing” mentality that prevailed at the time. While everyone wanted the whole loaf of bread, the arrival of AZT brought the first slice. Many scientists quote Voltaire: “The perfect is the enemy of the good.” The drugs we have today that target the interaction between viral enzymes and our cells are a product of this new kind of thinking. AZT was the drug that started it all.