This month, as we look towards the future of AIDS activism, I would like to share the following speech given by noted AIDS activist Gregg Gonsalves. His views on treatment activism clearly explain not only how important this issue remains if we have any hope of ending the AIDS pandemic within the next 25 years but also give an excellent overview of how much time, effort and thought go into effective and responsible activism. It is my hope that his example will serve to influence not only the next generation of treatment activists both here and abroad, but also inspire current activists and advocates in our ongoing work to end AIDS.
ASP Senior Director of Advocacy & Communications
Good morning. My name is Gregg Gonsalves. I work for an organization called the AIDS and Rights Alliance for Southern Africa, which is a network of human rights and AIDS groups throughout the SADC region. I am HIV positive and have been so for over a decade and have been on antiretroviral therapy since 1996.
I wanted to thank James McIntyre for inviting me here today. At first, I begged off. I told him he should have someone from the Treatment Action Campaign give this talk, but he insisted on having me, so instead of Zackie Achmat, Sipho Mthathi, Linda Mafu, Mark Heywood, who are all far more scintillating speakers than I am, you get a cheap imitation. As James' and my friend Polly might say, you're getting a Prada knock-off instead of the real thing.
I want to talk about rationality and irrationality today. And if you think I am going to talk about your health minister, I am, but this battle, between these two forces, spans countries and continents. It isn't just about health ministers and presidents, but AIDS activists, and sometimes, yes, scientists.
I've been doing this work for a long time. Not as long as Chip Schooley, because he is far much older than I am. I started this work back in the late 1980s. We didn't have the tools you have at your disposal today. AZT had only been approved in 1987 and nothing seemed to be able to stop the waves of dying friends all around us.
Back in the late 1980s, I fell in love for the first time in my life; he was a smooth-talking, charming man from New Orleans and he swept me off my feet. It was shortly after we met, though, that he told me late one night that he had AIDS. This was the first time in my life, my sheltered middle-class existence, that I met someone with AIDS. I wasn't afraid; in fact, I told him I'd love him no matter what and we moved in together shortly afterwards. No matter what. One morning he called me into the bathroom and directed me to look at the roof of his mouth -- there was a set of small purplish lesions up there and I panicked. I needed information; I needed to know what was happening. There was no internet to run to, we didn't have doctors, we didn't have health insurance, we didn't know what to do.
To cut a long story short, my partner didn't turn out to have KS, and as far as I know he is still alive and well somewhere back in New Orleans, but this incident led me to ACT UP, the AIDS Coalition to Unleash Power, a group that was started in New York City in 1987 and which revolutionized how we think of disease, of patients, of public health.
We did a lot of toyi-toyi-ing in ACT UP in the 1980s. We had many, many demonstrations. We were angry, so angry that while we watched our friends, our colleagues, our lovers, our families dying all around us, we had a government who seemed as if they couldn't care less about what was happening to us because we were gay, black, poor, women, junkies, whores.
But we changed the world. I was always interested in treatment, but as I said our options were limited back then. But I fell in with a group of people within ACT UP, the Treatment and Data Committee, who were fighting for it nonetheless. And our protests worked; the FDA, our MCC, sped up drug approvals, allowed the use of gancyclovir and aerosolized pentamadine on compassionate use basis (sort of like a section 21) and a parallel track, or expanded access programme, was established starting in 1989, and allowed Bristol Myers Squibb to distribute the experimental agent ddI to 25,000 PLWHAs until it was formally approved in 1991.
But it wasn't enough, and our work turned to research. We needed better drugs, we needed to stop the carnage all around us and we knew that scientists had the answers, they just weren't working fast enough, or weren't pursuing the right path, or so it seemed, when we "Storm[ed] the NIH (National Institutes of Health)" in 1990, and 1,000 protesters demanded more AIDS treatments, especially for the opportunistic infections that kill PWLHAs, an end to the under-representation of women and people of color in clinical trials, and the formation of a Women's Health Committee in the AIDS clinical trial system at the NIH.
But a funny thing happened around that time. Dr. Anthony Fauci, the Director of the National Institute of Allergy and Infectious Diseases, let us in the door, opened the door for us to research, and let us come to meetings of the AIDS Clinical Trials Group. If we had changed the world, now the world of research was going to change us.
I blame the statisticians. I'll name names: David Byar, Victor de Gruttola, Susan Ellenberg, Paul Meier, Richard Peto, Tom Fleming, Jim Neaton. It was the statisticians that taught us how to look at data, to weigh claims against evidence. Once we knew about randomization, controls, p-values, confidence intervals, post-hoc analyses, bias, we were even more dangerous -- woe to the researcher who fiddled with the numbers, or as my colleague Lynda Dee used to say, tortured the data until it confessed and told them what they wanted to hear!
AIDS Clinical Trials Group Study number 155 was a particularly egregious example. At the time, based on laboratory results, researchers believed the best combination therapy approach was dual therapy with AZT and ddC. ACTG 155 took people who had been on AZT for more than six months and randomly assigned them to continue AZT, add ddC, or switch to ddC monotherapy. The results showed that people did no better if they added or switched to ddC than if they simply stayed on AZT. Instead of admitting that combination therapy failed in this AZT-experienced population, the ACTG 155 protocol team conducted a post hoc subset analysis and tried to show that combination therapy benefitted those who entered the study with over 150 CD4 cells. Unfortunately, the study was not designed to look at subsets in this way, and there were too few endpoints in this stratum to reliably demonstrate anything.
At the International AIDS Conference in Berlin in 1993, the investigators presented their post hoc subset analysis, and the activists angrily denounced them for presenting an "intention-to-cheat" analysis. And over the years there have been other studies that earned our scorn -- the most recent example being the study of VaxGen's gp120 vaccine which in 2003 though found ineffective, was reported by the researchers to show efficacy in black, Asian and 'other' non-white ethnic groups within the trial. Guess who was data-dredging again! As one of our mentors, Richard Peto taught us, do enough post-hoc, subgroup analyses and you're likely to find the answer that suits your needs. His famous example was from the ISIS trials of aspirin in cardiovascular disease in which the overall statistical benefit for aspirin over placebo was extreme (P <0.00001), but the division of participants into only 12 subgroups based on the signs of the Zodiac threw up two (Gemini and Libra) for which aspirin had a nonsignificantly adverse effect.
But we made mistakes too -- we opposed a key study of combination therapy, ACTG study number 175, nominally based on the idea that it was underpowered to detect a difference between the four arms of the study, but largely because as one of my colleagues said back then: "we thought the trial a wholesale waste of time ("You don't combine 2 drugs with the same mode of activity -- like ampicillin and penicillin," one researcher told me)." How wrong we were.
But all in all, AIDS activists-some AIDS activists-were utterly changed by their experience with research. We learned that evidence was the key to moving us forward in the epidemic and that science, when rigorously conducted and reported, and when public policies were guided by science, we would make progress. We don't have a cure or a vaccine but science has brought us to where we are today, talking about treatment for the millions who need it in this country.
But not everyone is a fan of science.
Back in the early 1990s, we fell out with our colleagues at ACT UP, about the ACTG study number 076, who wanted the study stopped and for them, even discussions about the study with researchers were off-limits. Of course, this was the study that showed that AZT administered during pregnancy and to the newborn infant, cut transmission from mother to child by two-thirds. In fact, our colleagues in ACT UP seemed to be more and more suspicious of our "consorting with the enemy," the research establishment. It was this fact that led many of us to leave ACT UP.
We still have activists today who are deeply suspicious of research. Many of them are from marginalized communities, sex workers, drug users, people of color, the poor and we have to work to gain their trust. There are real issues, real histories of exploitation that we have to confront to do this. We have to teach each other about research; most people in the world don't have the privilege of the education that many of us have had, but can understand complex information if given the chance. TAC is doing this through their treatment literacy programme across the country, and I know it works, because I have seen it.
We have to address the real complexities and difficulties in clinical trials in developing countries, particularly the issues of post-trial care, informed consent, community involvement in research, and ensure that ideological, un-scientific nonsense that plagues some studies, such as when clean needles are banned from HIV prevention trials for drug users, is put to a stop.
But we also have to say no to people who put ideology ahead of science, we need to stand up for reason and rationality, in the face of dogma, irrationality, quackery, and the politics of pandering to religion and ethnicity that are willing to sacrifice the truth for votes or political expediency.
Let's though start with my own people -- the AIDS activists -- and George Bush.
At the recent International AIDS Conference in Toronto in July, a group of activists from ACT UP Paris, held a protest against a trial called the Development of Antiretroviral Therapy in Africa, otherwise known as the DART study. Paula Munderi, who is here today, is one of the investigators working on this key piece of research, which you have seen today has taught us a great deal already about using ART in Africa. The demonstration involved disrupting the speech of James Hakim, a researcher involved in a DART trial site in Zimbabwe. The protesters held up banners saying "Shame" while also demanding information about the deaths in the study -- information that has been readily available on the trial website since May 2006. Furthermore, they suggested that the scientists involved in the DART study put trial participants at risk of illness and/or death and made other charges of improper conduct against the DART investigators. A meeting between local activists and investigators in Kampala along with trial participants a few weeks ago made it clear that the "controversy" around DART was a manufactured one. Since these claims were "made in Paris", let's talk about them.
Let me be clear -- there is no evidence to support ACT UP Paris' claims that the informed consent process did not offer adequate information to the participants on health risks associated with the study or that any participants are excluded from the offer for post-trial care. ACT UP Paris also either misunderstands or is willfully mischaracterizing some components of the study and the available research on structured treatment interruptions. The DART study does not deprive any participant of laboratory monitoring of their HIV infection. The trial is an investigation of laboratory monitoring vs. clinical monitoring in the management of antiretroviral therapy to see what is the most effective strategy for use in resource-poor settings where laboratory capacity is often minimal or nonexistent. However, participants in the "clinical monitoring" arm are indeed getting laboratory monitoring, except that the results are blinded for both the participant and their doctor until the study is concluded unless there are significant laboratory abnormalities that would require clinical intervention. There is also no correlation at all in the literature about low CD4 nadirs, structured treatment interruptions and increased risk of disease progression as ACT UP Paris suggests. In fact, two key studies, SMART, the largest treatment interruption study conducted to date (>5,000 participants), found no association between CD4 nadir and the increased relative risk of progression and death that was seen among people taking long (~18 months) CD4-guided treatment interruptions. Likewise, in the ongoing Trivacan STI study in Cote D'Ivoire, there has been no association found between the increased risk of events and CD4 nadir. In a pamphlet on the trial, ACT UP Paris has also stated that there was a "1% death rate in the STI arm." This falsely suggests that there was excess mortality in the structured treatment interruption arm, when in fact there were 5/408 deaths in the STI arm and 4/405 deaths in the continuous therapy arm. Sadly, as we'll hear later today, we've learned from research on STIs that this strategy probably won't be useful for PLWHAs.
ACT UP Paris' actions have been shameful, not James Hakim's, Paula's or the other investigators involved with this study. In fact, ACT UP Paris, despite their claims to be supporters of research, are turning out to be its worst enemies. They have shut down studies of tenofovir in Cameroon and maraviroc in Europe, based not on evidence, but on their own ideological assumptions, their willingness to accept unverified claims as fact, their ignorance about study design and conduct, and as my colleague Bob Huff has said, a inclination to put their own individual beliefs above a careful consideration of the specifics of the drugs and the science.
And now for my President Mr. Bush.
Most of the rest of the world may have not noticed, but as he conducts his war in Iraq, he is conducting a war on, an all-out assault on, science at home, installing ideologues at key research institutions, while his government or its surrogates challenge basic facts about the efficacy of condoms, make claims about abortion causing breast cancer, claims that there is no link between lead exposure and cognitive problems in children, or between CO2 emissions and global warming-all to suit the politics of his cronies in the religious right and in corporate America.
We need to stand up against the forces of irrationality and madness -- whether it is ACT UP Paris, George Bush or your Health Minister.
I hope you leave this meeting this week ready to join the Treatment Action Campaign in its battle to see this minister dismissed and frankly to ask serious questions about why the President of this country continues to retain her despite her outlandish claims and support of pseudoscience.
But I also hope you stand up against the claims of charlatans like Matthias Rath who peddle garbage in communities around this country; traditional healers who make claims beyond what is supported by evidence about what their methods can and cannot do. There is no "Western" science and "African" science; there is science. Whether it is George Bush pandering to the religious right or your own politicians pandering to nationalism and ethnicity, it is pandering all the same.
We are in this together -- doctors, scientists, nurses, pharmacists, laboratory technicians, people with HIV/AIDS, AIDS activists. We need to stand up against the madness all around us. Galileo, when he was forced to recant, kneeling, all of his proofs that the Earth, the planets moved around the sun, as he stood up, he whispered "É, si muove!" And, yet, still, it moves. Say it loudly. Tell the truth. Abide by the evidence and let it guide you.