Kirsty Machon questions the misinformation, controversy and conspiracy theories which put an end to the proposed PREP trials among sex workers in Cambodia and Cameroon.
In the 1980s, molecular biologist Peter Duesberg made headlines with the extraordinary claim that HIV was not the cause of AIDS, but a harmless retrovirus that had been effectively the scapegoat for immune damage really caused by aberrant sexual lifestyles and amyl nitrate. It was a preposterous proposal, now thoroughly discredited. Its effects, however, have been in many ways profound: on the Internet, you can still find conspiracy theories and books peddling the line that HIV doesn’t cause AIDS, or is an ‘invented’ virus designed to poison entire continents or populations with toxic pills.
More recently, there’s been an international outcry over proposed trials of the HIV antiviral tenofovir as prophylaxis against HIV infection among sex workers in Cambodia and Cameroon, and high-risk groups in several other countries. On August 11 last year, the Cambodian government effectively scuttled proposed research, following protests from a local sex worker organisation, and pressure from self-styled international ‘activists’. The trial would have been sponsored by the US National Institutes of Health, using money from the Bill and Melinda Gates Foundation. The protocol was developed by the University of San Francisco, California, Australia’s National Centre in HIV Epidemiology and Clincal Research (NCHECR), and the Cambodian NCHADS.
What initially sparked the controversy were concerns the sponsors would not provide insurance to treat any drug side effects or related health problems for the 30 years following the trial. In a country where there is no common law right to sue for damages, it seemed legitimate to ask how participants would be compensated for any harm done. But what followed was an extraordinary global jeremiad of claim, and counter-claim, misinformation and disinformation, grandstanding and posturing, which has seen proposed tenofovir prevention studies abandoned in Cambodia, and in doubt Cameroon and other countries – and which could seriously hamper the HIV research effort in resource-poor countries at a time when it is needed more than ever.
I choose my terms here deliberately. Initial concerns over the proposed Cambodian studies were raised on the ground by sex workers themselves, but their cause was taken up with a vengeance by some individuals and organisations whose motives seemed to have a lot more to do with an entrenched grudge against the Western pharmaceutical industry and the opportunity to steal cheap headlines than any real care for what was at stake. Leading the charge, predictably, was the belligerent ACT UP Paris (a small, largely unrepresentative but miltantly strident group), which whipped up protests at last year’s World AIDS Conference, and inspired a farrago of paranoia, conspiracy theories, and pure lies about the proposed tenofovir trials, which very quickly got out of hand.
There are significant and complicated ethical issues involved in randomised controlled studies of prevention technologies – especially in resource-poor settings. But the tenofovir ‘scandal’ obscures, rather than illuminates, the stakes, and the legitimate ethical concerns. Much of the material which has circulated via the Internet has been based purely and simply on misinformation – a spectacular example of how the combination of ideological blindness, emotional intensity and headline-grabbing can come to seem more compelling than the prosaic truth, particularly in the age of email.
It has been claimed, for example, that tenofovir is an “experimental” agent (it is the use, not the agent which is experimental). It has been suggested that the manufacturer of the drug, Gilead Sciences, have been involved in dubious if not corrupt relationships with researchers, that women who seroconverted on the Cambodian studies would not be offered HIV antiviral treatment, and so on.
That these claims have been reported and repeated by so many, with no apparent attempt to consult the actual protocol, informed consent and trial materials, speaks volumes. This has not bothered the zealots one whit. Some commentators appear even to have had a mischievous interest in maintaining the confusion, rather than working with communities to ensure that potential participants are able to conduct conversations with the research agencies, develop better protocols, and make informed choices on behalf of themselves and their own peers. And by and large, these firestorms are not being whipped up in the communities where the studies would take place, but often by other activists and individuals often far away—in Europe, say, or the United States.
Tenofovir is a licensed HIV treatment, widely used around the world. It’s regarded as a potentially valuable candidate drug for HIV prevention because it is dosed once daily, is highly potent, has a resistance profile which is quite unique and unlikely to confer resistance to other drugs, and has fewer side effects than many other treatments. This is not to say that using tenofovir would be without risk – but one of the important purposes of the proposed studies is to determine if the risks of taking once-daily anti-HIV drugs in HIV negative people are indeed outweighed by any benefits it might show in preventing HIV.
At a time when more than 40 million people around the world are HIV infected—and 14,000 more become infected each day—this is surely an urgent question. There are many people wedded to the belief that behaviour change alone can and should drive down infections – but the stark evidence of the global pandemic is a compelling reply. While there have been significant successes, it must be noted that in many settings, behaviour change has demonstrated only a limited effect against the spread of HIV. It’s called the ‘real world’, where, for example, sex workers often find it very difficult to persuade clients to wear condoms, or may be offered considerably more money to dispense with them altogether.
It’s highly unlikely we’ll see a HIV vaccine within the next ten years. Some believe it may never happen, given the extraordinary scientific and practical difficulties. So attention has necessarily turned to antiviral agents as a potential preventative tool. There is evidence to suggest it could work. Post-exposure prophylaxis (PEP) has clearly prevented many infections, and the routine use of antiviral therapy during childbirth and postpartum has dramatically reduced mother-to-child transmission. If this is so, it’s entirely plausible that tenofovir or other antivirals taken before exposure could work to prevent the infection of cells exposed to HIV.
Randomised placebo-controlled trials are much more ethically loaded in the context of prevention. Because you’re working with people at genuine risk of HIV, and an agent which may or may not work, there needs to be an important emphasis on risk reduction counselling, and access to prevention technologies like condoms or clean injecting equipment. Any study which does not protect its participants with these basic safeguards should not get to first base, an important argument against proposed studies in Thailand, among injecting drug users, where clean injecting equipment would not be provided – largely due to outrageous US policy.
In addition, there’s the question of what happens to people who may become HIV-infected during the study, and the need to provide any appropriate proven treatment, including antiviral therapy, to trial participants. (This issue is particularly complicated in countries which don’t already have fairly widespread access to cheap or free antivirals – but surely it’s critical for the future of PREP research that these discussions are furthered by, rather than kill off, research proposals).
It has been falsely claimed that neither of these protections were in place for the proposed tenofovir PREP trial in Cambodia. This is simply not so. The trial protocol, for example, states explicitly that tenofovir is not proven to prevent HIV, has clear counseling guidelines for safer sex, and provides condoms for all participants. There is a lengthy discussion about safety, risks and benefits, including side effects, and the trial is designed to answer the question of safety as much as efficacy.
The women would be give priority for antiretroviral treatment through qualified clinical HIV services, including treatments for any opportunistic infections, and antiviral treatment.
It has been widely mis-reported that Women’s Network for Unity, representing sex workers in Cambodia, had been demanding 30 years of full general healthcare for study participants. Had this been so, there would have been serious ethical questions raised, as this could be seen as effectively an inducement to participate, in a country where health care is scandalously poor.
In fact, what the women sought was compensation for any harms potentially arising from the study. This is a requirement of the Australian and Cambodian ethical guidelines at the start of any trial. But for various reasons, the NIH apparently would not consider the proposal to implement this in the trial. What is clear is that the issue was on the table as the protocol was being finalised, and at the time the trials were stopped. But then one of the most frustrating aspects to this debacle has been the willingness of some commentators to paint those involved in the research as, effectively Western vampire-doctors and arch-villains of capitalism unrestrained, preying over the prone body of a victimised ‘developing world’ in the name of greed or the trajectory towards a Nobel prize. It’s a terrible, evocative, powerful image – a spectre haunting all debates about research conducted in resource-poor contexts.
Many in resource-poor countries are, understandably, hugely suspicious of research conducted by international pharmaceutical companies and US agencies. There is a history of ethical double standards, the imposition and manipulation of cultural policies and values – and all too often, those who have participated in the research are among the last to benefit from its results, if they ever do. For all these reasons, the involvement of local communities at the earliest stages of research development needs to be encouraged, and we should take seriously the evidence and views of those likely to be affected by research. On the other hand, the research arguably most likely to benefit countries like Cambodia and Cameroon would be that leading to a cost-effective and practical form of biomedical prevention – and it would be to the shame of all of us if the outcome of the tenofovir PREP experience is that this research should never be able to take place in the very settings where it may save most lives.
‘Why don’t the researchers conduct these “experiments” on people in their own countries?’ has been a repeated refrain over the last few months. In fact, tenofovir PREP is being trialled (for safety) among gay men at high risk of HIV in Atlanta and San Francisco in the US. Initial proposals for a similar trial in Sydney were mooted, but have so far not materialised. Even these early discussions ignited some perhaps knee-jerk negative responses locally – a real pity, given that high-risk gay men are probably likely to be most invested in the outcome of PREP trials, and hardly a helpful signal to countries like Cambodia, where the Australian NCHECR is a major partner in the research.
Still, there are compelling scientific reasons for conducting population-based prevention studies in settings with higher HIV incidence and prevalence than Australia. This is a concept often poorly communicated. But one of the most singularly exasperating aspects to this whole debate has been the very public questioning – I almost said inquisition – of the motives and intentions of agencies and individuals involved in the research.
High-handed commentators have been only too willing to paint the researchers, the drug, or any who defend it as pretty much Satan’s handmaidens. The Cambodian Prime Minister himself weighed into this debate, slamming the studies as unethical experimentation on Cambodian guinea pigs – and yet no one was brave enough to demand that he be held to account for the HIV epidemic in his own country, or indeed, to ask what the Cambodian government is currently doing to protect sex workers who stand a serious chance of becoming HIV infected within one year of commercial sex work. Far easier for commentators to take cheap shots at the obvious targets: drug companies, the US, clinical researchers—than to acknowledge that this is a debate of extraordinary complexity, the outcome of which we should all be invested in if we take seriously the future vision of a world without AIDS.
The initial randomised controlled trials of AZT in preventing mother-to-child transmission were similarly ethically challenging. No doubt, were they taking place now, they would have closed down by shrill commentators more intent on peddling their own ideological prejudices than in the facts of the matter. But the fact of the matter is that these trials provided an evidence base for an intervention that has saved the lives of many thousands of children.
The fact of the matter is that the HIV epidemic will not be fought and won if prejudice and posturing is able to prevail over reason, and misinformation and hysteria at the expense of informed debate. That’s not ethical – that’s the real scandal.
This article first appeared in HIV Australia Vol. 4 No. 3.