If you ask people in HIV/AIDS medicine to name the year that we turned the corner on the epidemic, many would say 1996.
For me, the medical landscape in 1996 shifted as the American social and political landscape had in 1968: There were so many momentous and emotionally charged events that, at times, it was hard to find the meaning within the tumult.
In 1968, things happened that once would have seemed unfathomable. First Dr. King and then Senator Kennedy were felled by assassins. Years of impoverishment shaped the Poor People’s March on Washington, D.C. Fury over America’s actions in Vietnam tore through the tear gas and bloodied police batons at Chicago’s Democratic National Convention—and television delivered all of it to our living rooms.
In 1996, leading researchers were achieving results with antiretroviral medications that were once beyond imagining: driving the virus to undetectable levels in patients’ systems and keeping it there, as nearly as we could tell, indefinitely. To an extent, I and others involved in clinical trials could say we had seen this coming for some time through our process of weeding out flawed drugs and protocols and refining promising ones. As it typically does, knowledge in the lab was running a year or two ahead of knowledge that could be applied—in this case, applied in HIV/AIDS clinics and broader patient populations.
Because we had an edge on the knowledge, I now realize, we also had an edge on optimism. We could feel reasonably hopeful because we could see that proverbial light at the end of the tunnel. But the patients and activists were in a place where they couldn’t yet see it. They were still dying and cursing the dark. And so they took also to cursing the research establishment—suspecting us, blaming us, attacking us—because we talked about prolonging life but they didn’t see it happening.
For me, 1996 was a dizzying year of internal conflict. I knew lives could be saved that would certainly have been lost. I knew it. And this knowledge did nothing to prepare me for the reality that, after investing my life in HIV/AIDS research care, I was seen by many as enemy more than ally.
If you’ve ever visited the Vietnam Veterans Memorial in Washington, D.C., you remember walking along the polished black granite walls sunk into the earth in a V shape. Where you enter, the wall is eight inches high. As the sidewalk next to it descends, the height of the wall increases until, at the walk’s lowest point, the wall towers above you, ten-foot-high slabs inscribed with the names of the lost.
To me, that landscape looks a lot like how the fight against HIV felt. For years we were in the throes of the epidemic, descending deeper and deeper—until, almost suddenly, we could turn 90 degrees and for the first time see the beginnings of a way out, a way forward.
That turning point, for me, had come in January 1995. That’s when I honestly felt we could begin to reclassify HIV/AIDS—that what had been a certain death sentence was becoming a chronic, manageable condition.
What did I see coalescing in early 1995 that led me to that conclusion? I saw progress on all fronts thanks to the collaborations of the pharmaceutical industry, academia, patients, activists, media, and key players in the federal government—Congress, NIH, CDC, FDA, and the Health Resources and Services Administration (HRSA), the agency charged with improving access to healthcare services for the uninsured and medically vulnerable.
The NIH provided strategic leadership through investment in basic science and clinical trials via their intramural programs and grants to individual investigators at academic medical centers and research institutes. The CDC provided continual monitoring of the epidemic and investment in tracking behavioral factors of transmission. The FDA helped by relaxing its previously rigid requirements for clinical outcomes (“body counts”) in HIV drug development, and the HRSA helped through its management of the Ryan White programs. Congress also played a key role in keeping the funding streams flowing despite occasional crises.
(Notice anyone missing from this list of federal players? When I credit those who hastened the transition of HIV from a death sentence to a chronic condition, notably absent are the 40th, 41st, and 42nd presidents of the United States. Ronald Reagan did nearly nothing during his eight years, when AIDS exploded onto the scene, thus giving the virus an enormous head start, despite his close personal and professional relationships with members of the heavily affected entertainment community. George H. W. Bush did close to nothing despite his claims that his administration practiced “compassionate conservatism.” Bill Clinton, during his two terms in office, was perhaps the biggest disappointment to me. I say that not because he did nothing, but because he voiced commitment to healthcare reform, science, education, and gay rights and yet never embraced HIV as a cause until he left office—meaning that he could talk about it but had no responsibility for it.)
Who did help bring about the turning point in the epidemic? The pharmaceutical industry contributed nonstop efforts to create newer, more potent, better tolerated, and more user-friendly drugs. Academia contributed creative, highly motivated, and collaborative investigators. The media contributed its generally sympathetic voice and persistence, a determination to keep the story alive even if the public was ready to dismiss it as “old news.” And the plague gave us patient after patient who offered to try any drug, suffer any indignity, bear any pain—if only their sacrifice might mean a better, longer, more meaningful life for others. I had a clinic full of people who willingly participated in clinical and basic science studies, though many were spending their last ounces of strength in the process.
But great credit also is due to the activists for their lack of patience. They kept everyone’s feet to the fire—industry, government, all of us—with their public insistence that “not enough is being done.” Their actions fueled progress, even when their words were hurtful to those of us trying our best. To many activists, our best was simply not good enough. And it wasn’t. Every time I lost a patient to the disease, I knew my best had not been good enough.
By the late 1980s and early 1990s, differences had sharpened among AIDS activists about what their goals were and how best to achieve them. In January 1992, activists Mark Harrington and Gregg Gonsalves left ACT UP to create the Treatment Action Group (TAG), a nonprofit organization focused on accelerating treatment research. They were hardly uncritical of the NIH, the pharmaceutical industry, and the academic community, but they took a different tack: They sat at the table with the establishment players, promoting institutional change from the inside while ACT UP continued to goad from the outside. TAG offered detailed analyses of how research and treatment could be improved. As Marty Delaney and Project Inform were doing, they injected urgency into the discussions and provided patient perspectives.
Meanwhile, direct-action AIDS advocacy was alive and well, and ACT UP founder Larry Kramer was its most prominent public face. His rhetoric was as stark as his group’s logo: the words “Silence = Death” under a pink triangle, the mark the Nazi Third Reich had placed on gays targeted for extermination.
Larry never hesitated to pursue his goals by employing what he considered the most powerful human motivator: fear. He wanted ACT UP’s words and actions to inspire fear in the scientists, the NIH, the White House, the pharmaceutical companies—anyone who might make things happen more quickly in HIV/AIDS medicine. He ridiculed high-profile investigators in public, often humiliating them in front of large audiences. Marty Hirsch at Massachusetts General Hospital was a favorite target because starting in the mid-1980s, he led the NIH’s AIDS Clinical Trials group, a multi-million-dollar network of academic treatment centers that collectively designed and carried out large clinical studies of new therapies.
I tried to set aside my feelings as an investigator and look at the situation dispassionately, but I still came to the same conclusion: ACT UP was acting out against the wrong people. The accusation that Marty Hirsch was “doing nothing” was a baseless assault; he was pouring himself relentlessly into his work. So were other leading MD-researchers in the field. John Phair of Northwestern University, Margaret Fischl at the University of Miami, and Larry Corey at the University of Washington were precisely the people who were making things happen. Tony Fauci of NIH pounded the pavement of Washington, D.C., and the doors of Congress to seek more funding to support HIV/AIDS research, and he was extremely effective. Of all the people the activists could attack, why them? Why us?
It is easier to understand why in retrospect than it was at the time. But not all activists are created equal. Some patients and activists genuinely believed they were being lied to about the science, that they purposefully were being given poisonous drugs or denied helpful ones. Some had embraced the work of Peter Duesberg, a University of California–Berkeley biologist who claimed that AIDS-related diseases were caused not by a virus but by the use of recreational drugs and even the use of AZT. Some activists—such as members of ACT UP San Francisco, a rogue offshoot of the mother organization—contended that HIV does not cause AIDS and that the use of antiviral HIV drugs only served to poison patients. They argued, therefore, that the pharmaceutical industry pushed “deadly drugs” just to make money and that existing drug therapies weakened rather than strengthened the body’s immune system and its ability to fight HIV.
Others who protested may simply have felt compelled to take some action, any action, in the face of all the death. My friend and patient David, the former fighter pilot, had explained this to me years before.
When Birmingham AIDS activists were marching on the 1917 Clinic demanding an experimental medication that we couldn’t provide, I had groused to David that they were ingrates—they were attacking the people who were trying to heal them. I can still hear his astute answer: “It’s not about you, Mike … It’s the white coat they’re marching on. It’s The Establishment, which you represent, like it or not.”
By January 1996, the good news I’d seen coming was ready for prime time. The venue was the annual meeting of the Conference on Retroviruses and Opportunistic Infections (CROI). The International AIDS Conference had become something of a political convention where political correctness and inclusiveness had trumped science and scientific presentations. CROI was created to focus on the most significant clinical science in the field. It had quickly become THE meeting at which to present new data. My Merck collaborator Emilio Emini was attending to present findings on triple-drug therapy, including data from the UAB study in which my patient Ben had first swallowed indinavir.
After Ben and others responded well to indinavir in small studies, Merck had scaled up production and was in the process of completing two so-called pivotal trials. The FDA and other regulatory bodies used these critical studies to weigh approval of new drugs, typically by comparing them to standard, approved treatments. In this case, Emilio was reporting on a large number of patients randomized to receive either AZT + 3TC or AZT + 3TC + indinavir.
The main floor of the ballroom at the Washington Sheraton Hotel was standing room only, so I made my way up to the balcony to watch the presentation. Emilio’s delivery was brilliant and his message was simple: The three-drug combination blew away the two-drug combo, no contest. Triple-drug therapy worked and unquestionably was the way forward. As I looked around the ballroom during his talk, the audience was listening intently. After Emilio, an investigator who worked with David Ho presented data from Abbott Laboratories’ protease inhibitor ritonavir. When combined with AZT + 3TC, it yielded results similar to our outcomes with indinavir in triple-drug therapy.
By the end of the session it was clear: The future had arrived. Presented before a large international audience, all could see the power of the triple-drug cocktail. It was easy to extrapolate the impact: Treat everyone with one of the three-drug regimens and they would live happily ever after. Mission Accomplished!
While the drug trials were underway, advocacy groups such as Marty Delaney’s Project Inform had been tracking trial results in real time. Seeing the promising outcomes from our indinavir trial, they began pushing Merck for immediate access to the drug. The company and the FDA balked, saying that the drug was too new and its safety unproven; for all they knew, the drug could kill people. To Tom and Marty, this was flatly ludicrous. Since the virus already was killing people, could a drug do any worse? And maybe, just maybe, it would save lives. The advocates put on a full-court press for accelerated approval of the drug for commercial use.
Hounded by Tom, Marty, and others, the FDA had approved both indinavir and ritonavir for use in HIV-infected patients by March 1996. The European regulatory agency, the EMEA, followed suit soon thereafter. Triple-drug cocktails were now available to patients who previously could have gotten them only within a clinical trial or through a compassionate use program. The entire process—from the “first-in-human” studies with Ben in the summer of 1993 to the FDA approval—took less than three years, compared to the five to seven years that such approvals ordinarily take. The FDA deserves credit for adopting policies to fast-track drug approvals. But in my opinion, the lion’s share of the credit for hastening the approval goes to the impassioned, relentless activists.
After the January CROI meeting, and even after the March drug approvals, I didn’t hear the kind of buzz that I had anticipated after such game-changing developments. It’s possible the findings were so stunning, like a reprieve for someone on death row, that it took time for them to sink in. For whatever reason, the conversation about new HIV therapies was pretty muted for about ninety days, April through June. Then, in July, the 11th International AIDS Conference opened in Vancouver, British Columbia, and all hell broke loose.
In the natural world, it’s called a “feeding frenzy” when wolves or sharks descend on a quarry with mindless, ravenous abandon. In the information age, I’ve seen a similar sort of frenzy in pursuit of headline news. A Twitter mob formed online in the wake of the 2013 Boston Marathon bombing, naming as suspects people who were totally innocent. As the Vancouver conference neared, journalists arrived in droves to cover the triple-drug therapy breakthrough. They came armed with preconceptions and superlatives, while the scientists and activists and drug companies came armed with their own, often deeply personal angles on the story. The emotion of the time fairly crackled in news reports. POZ magazine reported:
By the International AIDS Conference in July, the elation had reached such a frenzied pitch that longtime AZT investigator Dr. Paul Volberding was ambushed by a camera-and-microphone-wielding throng while checking into his Vancouver hotel. “Would you characterize the tone of this meeting as ‘euphoric’?” one reporter asked—even before the convention had officially started. Volberding demurred.
Amid the rush to declare victory, responsible scientists tried to strike a balance that reflected reality: We had new tools to prolong lives but we had no cure.
On July 10, reporter Elizabeth Farnsworth of the PBS NewsHour interviewed two distinguished conference participants: Dr. Helene Gayle, the CDC’s director of HIV prevention, and Dr. Roy “Trip” Gulick, a clinician and researcher at the New York University School of Medicine and a valued colleague of mine. In this exchange, Trip reflected the cautious optimism many of us felt.
FARNSWORTH: So, Dr. Gulick, is it too early to say that AIDS is no longer an incurable, inevitably fatal disease?
GULICK: Well, I think that what we’ve shown is using combinations of drugs which can actually lower the virus to very low or undetectable levels for periods as long as months, that what we’re really saying is that that’s an important first step toward making HIV a chronic, treatable illness. I think it would be misleading to say that we have the answer. Certainly I would not use the word cure to describe these therapies, but we’re making a positive step in the long-term treatment of this disease.
While PBS was interviewing Trip Gulick, I was preparing to be on a panel discussing the new antiretroviral therapies. The panel was organized by my old friend Donna Jacobsen, president and executive director of the International AIDS Society-USA. My panel mates were top-notch researchers and clinicians including Margaret Fischl, Paul Volberding, and Doug Richman, whose laboratory was among the first to identify HIV drug resistance. Because we were going to address the clinical basics of using these new drugs—when to start therapy, what to start with, when to change therapy and what to change to—the symposium drew a big, curious crowd. Doug was at the podium, partway through his presentation on primary infection, when the doors of the venue were slammed open and the circus began.
I’ve seen videotapes of the event, but they don’t really capture the scene as I felt it, chaotic and alarming and ridiculous all at once. Twenty young men from the rogue ACT UP San Francisco group burst into the ballroom, shouting unintelligibly. They ran down the aisles, mounted the stage, and slung containers of red liquid so it sprayed across us panelists. They doused us with fake blood, they later said, to make their point that if the researchers themselves were infected with the AIDS virus, that might spur more urgency and progress in fighting it.
Some of us sat there startled; others retreated from the dais as the protesters charged. They jumped on the dais, raised their arms in power salutes, and their shouts became rhythmic chants: “Toxic chemotherapy! Ban AZT! Toxic chemotherapy! Ban AZT!”
The conference center security personnel, showing a restraint I’ve long associated with Canadians, didn’t apply any muscle. But they did step in to position themselves between us and the demonstrators, who variously shouted at us, grabbed for our microphones, knocked papers and water off the dais, and pumped their fists in the air. Our audience of colleagues began its own roaring chant toward the unwanted protesters: “Get out! Get out! Get out!”
As a panel of MDs, we knew immediately that we hadn’t been showered with actual blood. Upon further inspection, we concluded it was probably beet juice. Margaret was among the worst hit, vegetable gore splashed on her eyeglass frames, her cheek, her blouse. I remember mentally cursing these clowns for ruining one of my favorite jackets, the one I had worn to my son Andy’s bar mitzvah. Somebody passed us a couple of tablecloths and we tried to mop up the area and ourselves.
After a few minutes, apparently satisfied that they had made their point, the protesters walked off stage with a security escort to a chorus of boos and shouts of “Shame!” A representative of ACT UP’s New York chapter came to the podium to apologize. He said the protesters were members of ACT UP San Francisco, the rogue band that had split from the official group, “and we disown them. We never disrupt information, ever.” Years later, Donna Jacobsen still was struck by “how very different this was from any other ‘activist’ activity. Rather than a demonstration or protest about the lack of progress, it was an attack on the dissemination of information. It was just unconscionable.”
A meeting organizer appeared with enough white VANCOUVER 1996 conference T-shirts for all the panelists. We took off the most soiled of our clothes, put the T-shirts on, and went back to our seats at the dais. I’ll always remember Doug Richman retaking the podium, straightening the microphone, and delivering the deadpan line, “Now, where was I before I was so rudely interrupted?” I still have my printed program from the symposium with its juice-stained cover.
I also still have something I received a few days after that symposium. It’s an email from Billy Pick, an HIV-positive man then working for the AIDS office of the San Francisco Department of Public Health. Billy wrote to both me and Margaret Fischl, saying that he had recognized our faces in news photos of the “blood”-splattered Vancouver panel “and decided to write. I want to express my outrage and sorrow that you had to be the targets for such unwarranted and misguided actions. I want you to know that the people who did this do not represent the HIV community in San Francisco …
“I wanted to thank the both of you for your commitment to people with AIDS because I don’t know if anyone else has or will,” Billy’s email continued. “It takes a tremendous amount of patience and character to deal with the pain and the anger that many of us in the community feel sometimes. It also takes a lot of courage to stand up to systematic abuse and terrorist tactics. I would ask that you continue to do so, not just because we need your scientific expertise but because I really believe that both of you care about finding a cure for those of us with this disease.”
As long as I was serving people like Billy—and I am, to this day—I could put up with all the hecklers and the beet-juice bombardments. (And thanks to an emergency dry-cleaning run by the resourceful Donna, my favorite jacket wasn’t ruined after all.)
The incident in Vancouver deserves not only to be remembered or criticized, but understood. It’d be easy to dismiss the protesters in Vancouver as crazy, their tactics as childish and counterproductive, their charges as ignorant nonsense, and their claims that HIV does not cause AIDS as bizarre. More representative are the other activists, like Larry Kramer, ACT UP New York, Marty Delaney, and Tom Blount. Their rage at The System was real and completely on target. Many times since then, I have heard other healthcare consumers—and not just HIV patients—express frustration and outrage. They can’t get the care they need. They can’t get the care they see others get. They don’t understand either their health problems or their health coverage. They can’t get a straight answer from a doctor, or even a call returned. They can’t afford care a loved one needs. Or they paid for the care, the loved one died, and the crushing debt lives on.
If I knew all this in vague, intellectual terms in the late 1990s, I know it now in the most intimate and personal of terms. Hour after hour in the 1917 Clinic, as elsewhere, the opportunity to care for people is thwarted by The System. Within the past seven days I have lost my patience, delivered rants, and felt the frustration of being denied the opportunity to treat and care for patients—felt it so keenly that I nearly wept. Perhaps now more than ever, I’ve begun to understand the origin of the activists’ action. It wasn’t so much about logic; it was about having nothing left to lose. More than anything, it was about grief.
There was plenty of progress against HIV in 1996, significant achievements and milestones. In 1996, the number of new AIDS cases diagnosed in the United States declined for the first time since the epidemic began. In 1996, UNAIDS (the Joint United Nations Programme on HIV/AIDS) was established to promote global efforts against the disease, and the International AIDS Vaccine Initiative was formed. In 1996, the FDA approved key consumer tools for HIV detection, including the first HIV home testing and collection kit. Starting in 1996, AIDS no longer was the leading cause of death for all Americans ages 25–44.
Optimist that I am, I could make the glass-half-full argument about 1996 and probably about every year since. I could say that when there’s been so much improvement, it’s ungrateful to dwell on what has not improved. But if we don’t look hard at the deficiencies, we’ll never force The System to come to terms with them. And we must.
I remember learning early in my medical training that surgery is, no matter what else you say about it, messy. It’s just a messy, sloppy, unappetizing process. So is much of medicine, frankly. We deal with human waste as well as human intake; we spend our days examining smelly sores and draining wounds. One of the reasons we use such incredibly Latinate terminology for simple procedures—colonic disimpaction, hemipelvectomy, radical debridement—may be to mask the unpleasant realities.
When most of us think of research, we think of sparkling laboratories where impossibly clean women and men wearing spotless white coats perform sterile procedures. When we think of advances in medical science, we think of heavily vetted journal articles and highly technical conference presentations delivered in a language and style that would cure the average insomniac. And all of this is, to some extent, true.
It’s also true that research is sometimes a messy process, despite our best efforts to clean it up. Research findings morph into journal papers and conference presentations, but they also make their way into the clinic where we’re out of bullets to treat Michael, and he’s going to die unless we have something new. Medicine doesn’t treat findings or reports; it treats Ben and Andy and Cyndie, and therein lies the source of its messiness. And research dealing with human suffering does not hover over the affected population and drop papers from the air. It, too, finds its way in front of glaring cameras and skeptical reporters and people who have suffered, are sick, are dying.
As ironic as it sometimes seems to me, the same phenomenon that drove protests led for over a decade by ACT UP and Larry Kramer—a public outcry, a scream for change, a patient-based revolution—might be needed today to address America’s failing healthcare system.
So long as “healthcare policy” is removed from those who suffer and die, so long as “healthcare financing” is measured in the bottom-line billions instead of Uncle Ted’s copay or Mom’s need for a home nurse, so long as the debate is conducted by those who are both well and well insured—we are going to continue spiraling downward with ever-declining outcomes and ever-increasing costs.
Turning the tide on this is going to take something stronger than beet juice. It may take a critical mass of Americans speaking out against the status quo.
Once after my old friend and “nemesis” Larry Kramer had chewed out someone at the top of his lungs, he was asked why he so frequently was heard screaming. His answer was absolutely convincing: “Because it hurts.”