Treatment as Prevention: Treating People to Death

There was an attack on 'treatment as prevention' in March which came from a person you wouldn't expect to oppose a technological quick fix, Elizabeth Pisani. Despite the fact that she disagrees with UNAIDS in some ways, she is an adherent of the behavioral paradigm. It seems a pity to hold views that challenge the mainstream and yet still cling to the mainstream's central premise about HIV: that it is almost always transmitted through heterosexual sex in African countries.

But it's worth citing her opposition to a strategy which has a lot in common with PrEP. Firstly, Pisani points out that "HIV is most infectious in the few months after a person is first infected. Even if everyone got tested annually, we’d miss most of these new infections." I hope the 'modelling' work that is said to support treatment as prevention includes this point, but I doubt it.

Pisani also notes that there are a number of circumstances under which viral load (infectiousness) can spike, such as contracting another sexually transmitted infection (or perhaps other diseases) or failure to take medication correctly, which can occur for many reasons. Such a spike would increase infectiousness in people who may well be engaging in unprotected sex.

Pisani refers to findings relating to treatment becoming more widely available in rich countries. Apparently rates of unprotected sex increases as a result of 'disinhibition', engaging in unprotected sex in the belief that the risk is now low. Many have claimed that disinhibition does not happen to any great extent in African countries. The 'model' used by proponents of treatment as prevention believe that disinhibition will not significantly contribute to HIV transmission and that adherence to drug regimes will be extremely high in African countries.

Pisani casts doubt on both of these claims. I have to say, I agree. I would suggest that the finding that disinhibition is low in African countries is more likely to indicate that HIV is not as closely related to sexual behavior as we have been led to believe.

As for claims about high levels of adherence, I'm not sure if figures for treatment in countries like Kenya and Tanzania are very complete or credible. Death rates among HIV positive people seem to be high enough to keep prevalence steady and there is no evidence that sexual behavior has been influenced greatly by behavior change programs.

I'd say UNAIDS, and Pisani herself, are over-optimistic about a lot of things. Treatment as prevention sounds, on the surface, like a good idea. But it's not going to be enough on its own, especially if only sexually transmitted HIV is being targeted. Waiting till people become infected and then treating them, hoping that they will all become less infectious and therefore slowing down the epidemic, is ludicrous.

Even if HIV is 100% sexually transmitted this would not work. We must know by now how hard it is to influence people's sexual behavior or, indeed, any other kind of behavior. But HIV is also transmitted non-sexually. It is vital to establish the contribution of non-sexual HIV transmission to serious HIV epidemics, otherwise sexual transmission will continue to be overestimated. As long as we overestimate sexual transmission, HIV will continue to spread.

Millions of Pills Haven't Worked So Let's Try Billions of Pills

The 'treatment as prevention' approach to reducing HIV transmission is getting airtime again, this time because the pioneer of the strategy has receive the Einstein award. Treatment as prevention is more of a hypothesis than a strategy or approach, really. But given the rarity of feasible HIV prevention strategies the HIV industry needs something to obsess about.

The hypothesis suggests that, because successful HIV treatment reduces the viral load to the extent that HIV positive people are very unlikely to transmit the virus, prevention programs could rely on this to significantly cut HIV transmission.

The number one flaw in the hypothesis is that it assumes that most HIV is transmitted sexually. This is a rash assumption in countries where health service provision is of extremely low quality. But the HIV industry has little interest in health or health service provision when they can sell lots of drugs. And it's a media friendly issue, with its combination of technical fix and the implication of illicit sex.

Of course, rolling out treatment to as many HIV positive people as possible when they need them is a good thing. But it may not have much impact on transmission rates. And ensuring that they didn't become infected in the first place would be preferable. It is hardly reassuring to those who are currently HIV negative that so little is going to be done to help them stay that way.

Another flaw is the assumption that a disease can be eradicated by some technical fix when the circumstances under which the disease became an epidemic are left pretty much as they are. So there is no need to improve health, education, infrastructure or social services? But these questions are not popular in the industry.

HIV testing has been around for some time now, in developed and developing countries. Most people never get tested, others test once and never again. But treatment as prevention requires the majority of people, or as near to 80% of people as possible, to be tested regularly, perhaps once a year.

It remains to be seen how many developing countries will be able to encourage such huge numbers of people to turn up for testing every year, or even how such programs will be administrated in countries where health services are so poor. High prevalence countries currently have a lot of trouble accounting for the HIV positive people they know about, a fraction of the total infected.

The above article on the award raises the issue of 'risk compensation', where it was feared that the availability of HIV treatment that also reduced infectiousness might result in increased risky sexual behavior. But where sexual behavior is not the main driver of HIV transmission, this is something of a red herring.

It's great to hear that treatment as prevention works so well in British Columbia. But I don't think the health problems in BC are anything like the health problems in East Africa. And I'm pretty sure the health systems (also education, social services, infrastructure) in BC are not like those in East Africa.

In short, the technology on its own is not the solution to an epidemic that has many determinants. This technical fix may have some impact in isolated pockets of East Africa, especially in randomized controlled trials, but people need a lot more than just pills to stay healthy. Far from obviating the need for decent health services now that some great technology is available, that technology requires adequate health services, and probably education, infrastructure and social services.

Why do Microbicide Trials Make No Effort to Establish Mode of Transmission?

In contrast to the CAPRISA vaginal microbicide trial, which received copious amounts of coverage, not so much is said about the PRO2000 gel trial. The latter trial was deemed safe but it did not prevent transmission of HIV to women.

As is customary in these trials, no attempt was made to establish how HIV was transmitted. It was just assumed that it was sexually transmitted and male partners were not tested.

Incidence was high, between 3.9 and 4.7 per 100 woman years, despite condom use being high. Condom manufacturers might even be a little bit curious as to why people who were not engaging in sex very much, were avoiding unsafe sex and had been selected because they were HIV negative, seemed to be so susceptible to HIV infection. They were even screened for other sexually transmitted infections (gonorrhea and chamydia).

The ostensible aim of microbicide trials will not have been achieved. In order to prevent HIV transmission it needs to be clear how the virus is being transmitted. Microbicides may have some influence on non-sexual HIV transmission but people are unlikely to use them to prevent infection when they are not having sex unless they are made aware of the existence of such risks.

And even then, people will not be choosing to use vaginal microbicides. They would not be the first choice if you were a man, going for an operation, visiting the hairdresser, injecting drugs, pregnant or about to give birth, getting a tattoo, etc.

The failure to establish mode of transmission is not just a flaw. Non-sexual modes of transmission may turn out to be responsible for a significant number of HIV infections in some epidemics, such as those in high-prevalence sub-Saharan African countries.

If so, vaginal gels may achieve little more than continuing to deflect attention from the abysmal health services that are undoubtedly infecting African patients with all manner of diseases, not just HIV.

Dear CAPRISA 004, You've Been Dumped

The most hyped issue by far at the hype-laden Vienna Aids Conference a few months ago was the CAPRISA 004 microbicide trials, which is said to be "at least 39% effective in preventing HIV infection" when applied before and after sex. There were calls for the technology to be made widely available as soon as possible, though the trial results are not impressive and several more years, at a minimum, are required before a viable product results.

On the strength of the hype, attempts were made to raise $100 million to carry out further trials. But only $58 million has been raised so far. What has happened to all the enthusiasm of a few months ago? Given his endorsement of technological fixes, especially pharmaceutical ones, why hasn't Gates coughed up the shortfall yet? And why is so much of the money coming from donors? Big Pharma constantly bleats about how much money they invest in products as an excuse for extorting enormous profits out of what is often publicly funded research. Where are they now?

Many African countries are finding just how quickly donors pull out when it suits them, although these countries were heroes in the fight against HIV only a short time ago. Far fewer people receive antiretroviral drugs than need them, many of them are lost to follow up, develop resistance, die of something curable or simply cease to be important now that HIV treatment on its own is no longer flavor of the month.

What could explain this sudden lack of interest? Will PrEP experience similar fluctuations?

Opportunity and Opportunism in the HIV Industry

There's an article in the July edition of the Journal of the International AIDS Society entitled "Planning for pre-exposure prophylaxis to prevent HIV transmission: challenges and opportunities". The list of 13 authors and their respective institutions reads like a page from a Who's Who of the HIV/AIDS industry. The tone of the article suggests that there is more interest in the opportunities presented by pre-exposure prophylaxis (PrEP); the challenges are made seem quite irrelevant, or at least surmountable. The paper emanated from a meeting sponsored by the Gates Foundation.

In addition to the apparent irrationality of trying to eradicate HIV by putting most sexually active HIV negative people on antiretroviral drugs (ARV), PrEP would seem to be in tension with another, slightly less irrational strategy: 'treatment as prevention'. Treatment as prevention involves treating everyone found to be HIV positive with ARVs, regardless of their disease stage. According to this theory, people who are on ARVs are not very infectious, so they are unlikely enough to transmit HIV for the epidemic to eventually be eradicated.

But a successful treatment as prevention program would obviate the need for PrEP. And a successful PrEP program would make treatment as prevention a serious case of overkill. Perhaps the industry, in its great wisdom, is not advocating for both programs to be implemented in the one place. But both strategies seem to be about maximizing drug use without having much likelihood of effecting substantial reductions in HIV transmission.

PrEP would target HIV negative people and treatment as prevention would target HIV positive people, so the latter would seem to be the more tractable aim. Even in the highest prevalence countries, there are more HIV negative people than HIV positive. But then you have to make the decision, assuming your resources are limited, as to whether you distribute drugs among those who are already sick, to allow them to live longer and to enjoy good health; or distribute drugs among those who are not sick, but who may become infected.

PrEP and treatment as prevention are not complementary strategies, they are clearly in tension. But the tension is not irresolvable. Healthy people don't need drugs. There are other prevention strategies available that PrEP can only overlap with, such as condoms and possibly others. There is also prevention of non-sexual HIV transmission, which has been totally ignored in developing countries so far. But the aim to treat everyone infected, no matter how desirable, will not guarantee the protection of people as yet uninfected.

The article concludes "It is an ethical imperative that we act now to prepare the path to timely implementation [of PrEP]". The only ethical imperative is that we find appropriate treatments and prevention interventions. The imperative to exploit the HIV pandemic to make huge profits is not ethical, whatever else it may be.

Betting on Sex

The behavioral paradigm, which claims that most HIV transmission in African countries is a result of unsafe heterosexual intercourse, is vitally important to the pharmaceutical companies competing to develop HIV drugs. Some HIV transmission is due to heterosexual intercourse, but it is not clear what proportion. Some transmission is also due to unsafe medical and cosmetic practices. But, according to those defending the orthodox view, sex is the problem and only a tiny proportion of the virus is transmitted through any non-sexual route.

Betting on the behavioral paradigm being true, the pharmaceutical industry has been working to widen their markets. They are not only targeting people who are HIV positive but also the far bigger, and more lucrative market, of those who are HIV negative. It is hoped that they can be scared into believing that they are vulnerable, and more to the point, that they need to take some form of drug to protect themselves.

Four of the main means of widening the market for HIV drugs are vaccines, microbicides, pre-exposure prophylaxis (PrEP) and a strategy called 'treatment as prevention'. A maximum of about five million HIV positive people in the world are currently on antiretroviral drugs (ARV). But tens of millions, perhaps hundreds of millions could be potential customers for vaccines, microbicides and PrEP. Even just one of these could increase ARV consumption by tens or hundreds of times.

Treatment as prevention, testing everyone regularly and putting anyone found to be HIV positive on ARVs to reduce their transmission rate, would create a smaller market, but it could still be about ten times the current market.

To help out the pharmaceutical industry a bit more, because they are clearly struggling to make ends meet, there are two further phenomena. The first is the new WHO Guidelines on HIV treatment, which recommend putting HIV positive people on treatment at an earlier stage of disease progression. This could double the current market. The second is the enormous levels of ARV drug resistance that will inevitably develop as a result of all the previous considerations.

Vaccines, microbicides, PrEP and treatment as prevention are all predicated on the behavioral paradigm. While any treatment with ARV drugs may give some protection against any kind of HIV transmission, no one is going to vaccinate against something that they could catch from unsafe medical or cosmetic practices. They will just insist on safe medical or cosmetic practices. No one would put a topical microbicide on their genitals to protect themselves from accidental exposure to contaminated medical equipment during an operation. And people certainly won't be taking PrEP before going to the doctor, dentist, hairdresser or tattoo artist.

If a significant proportion of HIV transmission is as a result of unsafe medical or cosmetic practices, that would really cut into the markets that Big Pharma have been trying to secure for so long. The whole HIV industry and the hoards of academics, consultants, bureaucrats and countless others that work so hard to claim that sex is the problem would have to find other approaches to cutting transmission.

True, it would be far easier to cut transmission if a lot of it turned out to be non-sexual. But easier for whom? Topical microbicides and the like can't be used for much else aside from preventing sexually transmitted HIV. I'm sure there'll still be vast markets for HIV related pharmaceutical products. But without sex, will anyone even care any more? It's hard to imagine who will want to be involved in HIV prevention campaigns without the current emphasis on sex, whether they come from a moral, population control, religious, political, salacious, commercial or almost any other angle.

I don't wish to exaggerate, I'm sure sex plays a big part in HIV transmission. But the world needs to know just how big that part is. And that means investigating the part that non-sexual HIV transmission plays in high prevalence countries. Simply guessing, which is what UNAIDS currently do, is not good enough. People are entitled to know how HIV is being transmitted so that they can protect themselves and others.

The HIV industry, if it is ever to have an impact on the pandemic, also needs to know. They need to let Big Pharma fend for themselves, they'll probably be OK. But many people are being infected with HIV, suffering disease and stigma and passing the virus on to others because they don't know that they can be infected through non-sexual routes and so they don't know how to protect themselves. It's time for the industry to admit they got it wrong, that it's not all about sex, and to start doing something about it.

Beware of What We Don't Know About PrEP

It might be thought that if HIV were one day, not just preventable, but also curable, that prevalence in most countries would go down very quickly and anyone infected in the future would be cured, sooner or later.

But are all preventable diseases prevented, where possible? And are all curable diseases cured? Cholera, malaria, polio and a huge range of other diseases can all be prevented by provision of clean water and good sanitation and most of them are curable (although clean water is also required for this, not just drugs). Yet water-borne diseases are endemic in many countries and kill vast numbers of people. And polio, despite considerable efforts, some successful, just keeps coming back, to a large extent because people keep drinking water contaminated with sewage.

So why should pre-exposure prophylaxis (PrEP) for HIV be any different? Perhaps HIV is seen as politically important. Well, it certainly is politicized. But then, a massive cholera outbreak in Zimbabwe last year was also politicized. It received a lot of attention, one suspects, because Zimbabwe and Mugabe were receiving a lot of attention.

Cholera outbreaks are a reflection of very poor water and sanitation provision. The failure to deal with such an outbreak efficiently reflects badly on the strength of the country's administration and on the strength of their health services.

However, the cholera epidemic ceased to interest the world's media, perhaps because it eventually petered out, as epidemics sometimes do. Water and sanitation provision are unlikely to have been improved much, the same probably applies to health services. As for the administration, all that can be said is that the medial has gone off to ogle at something else.

How long will it take the world's media to focus on the current cholera outbreak in Nigeria? Perhaps the political situation is not considered interesting enough at the moment, but as a health story, it doesn't seem to have got around yet. Ok, the story is getting around now, but mostly among the African and NGO press. It has even appeared, briefly, in the mainstream media, but it has not been very widely covered, given the implications of such an epidemic.

When the media does get around to covering the outbreak, it will probably concentrate on the sheer magnitude, rather than the conditions that allowed the outbreak to become an epidemic. The media may even reflect on the irony of such an epidemic occurring when it's so easily predicted and prevented.

We know the conditions under which cholera outbreaks become epidemics, the determinants of such large scale health emergencies. We know how to substantially reduce the probability of such an outbreak and how to prevent it from escalating. You will find the perfect conditions for outbreaks of cholera and other water-borne diseases in most countries in Africa, right now.

'Emergencies' are not always unforeseen events. We might not know when and where they will occur but we always know the sort of places where they might occur, the conditions under which they will occur, given time. We usually have (or could easily obtain) a good idea of how many people are vulnerable to injury and death if they do occur and how to improve the conditions to the extent that an outbreak can be contained and people treated until their health is restored.

People needn't suffer from and die from many of the preventable and curable diseases that they do suffer and die from. But we also have the capability to provide HIV positive people with palliative care so they don't have to suffer unnecessarily, yet many don't receive such care. Many people who need antiretroviral drugs (ARV) either don't receive them or fail to keep on taking the drugs. In other words, many people suffer from and die from Aids, unnecessarily.

Even if HIV PrEP were a reality, and it is far from that, why should we believe that the practicalities of distributing such drugs to the people who need them, when they need them, for as long as they need them, will ever be part of the intention of those who keep screaming about how important PrEP is? Being able to do something is not the same as doing it, or having any intention of doing it.

If PrEP advocates would be a little honest and balanced in their arguments, I might give them some credence. But it is the very absoluteness of their pronouncements, the purity of their stated intentions, the apparent goodness and even the applicability of PrEP to the world that makes me think that the whole thing is part of a broader aim to vastly increase sales of relatively useless pharmaceutical products to people; any people at all.

One of the most worrying aspects of PrEP and HIV is that, unlike water-borne diseases, we don't know why such huge numbers of Africans become infected with HIV. We know that people who are members of some demographic groups in some countries are more likely to be infected than people from other demographic groups and countries. But we are not certain, despite assurances to the contrary, why this is so.

Everyone drinks water and most people have sex. Only some people drink contaminated water and only some are likely to have sex with a person who is HIV positive. But in most demographic groups in most countries, the likelihood of becoming infected with HIV, despite having regular, unprotected sex with someone who is HIV positive, is very low. Until we understand why this is so, PrEP will be of little use, if any, in high HIV prevalence countries.

The Opposition is Real, it's the Defense that is Fabricated

In an article entitled "The Abandoned Trials of Pre-Exposure Prophylaxis for HIV: What Went Wrong?", Singh and Mills make the very assumption about PrEP that they are not in a position to make: that it may be useful for women involved in commercial sex work. As is clear from a number of studies, high prevalence of HIV is not very closely related to sexual behavior nor to 'high risk' groups, such as commercial sex workers.

Therefore, we are still in the dark about how PrEP should be used. Making PrEP available to low risk groups would be ridiculous, but I think that is what the pharmaceutical companies involved would like; to put lots of healthy people on drugs that they need to take in large quantities for much of their adult life.

The authors of the paper try to use seemingly reasonable arguments and suggest that the industry needs to be 'proactive' in its dealings with those who oppose the creation of markets for useless pharmaceutical products, taking advantage of cheap research subjects in developing countries. But by 'proactive', they seem to be recommending that the industry get in quickly and preempt any potential opposition.

They talk approvingly and rather naively about the involvement of the Bill and Melinda Gates Foundation in getting both sides together, as if the foundation is anything other than a major part of the HIV industry that stands to profit handsomely from its investments in Big Pharma.

Differences between activists and the HIV industry are not mere 'ideology'. Activists are not convinced that PrEP has anything to offer anyone but the pharmaceutical industry. Yes, the goal is combating Aids and the target is people who are HIV positive (and those who are at risk of becoming infected). But PrEP is irrelevant to both of those. So activists will continue to oppose it.

Drugs for the Healthy, Drugs for the Sick, Drugs for those In Between

Joep M A Lange expresses his frustration about protesters 'derailing' trials of PrEP a few years ago, referring to the halting of the trials in Cambodia, Cameroon and Nigeria. He wishes that protesters would all operate under some kind of umbrella, presumably so they can all be bought off all at once, like himself. But there is a good reason why protesters do not operate under an umbrella organization: they often have very different agenda.

And there are many reasons for questioning the use of PrEP as an ostensible means of reducing HIV transmission in developing countries. Some would argue that health is not purely a matter of disease eradication and they object to the medicalization of health, where people dying of water borne diseases are given drugs which they swallow using contaminated water.

Others might worry about the side effects of taking drugs, especially for healthy people. Then there's resistance, where people taking PrEP might be or become infected with HIV and resistance would develop. They would have a difficult and expensive to treat strain of HIV, which they could easily transmit to others. The 'cure' would have made things a lot worse.

These are all legitimate worries and they all need to be on the drug companies' agenda, whether they like it or not. They can't be relegated to any other business, crowded under an 'umbrella', to be treated with the same contempt that the pharmaceutical industry treats people in high HIV prevalence countries, HIV positive and HIV negative alike.

But there are two other worries I'd like to highlight here: firstly, Joep raises the issue of 'female-controlled' prevention techniques (though he says technologies because it musth be high tech, right?). The drug industry likes to point out how terrible the plight of women and children is and how men are so unreliable and badly behaved and that they are making PrEP available to help the most vulnerable people in high HIV prevalence countries.

But this is an argument for researching the issue of disempowerment and ways of alleviating it. Of course, drug companies may not have a big part to play, you certainly can't cure those problems with a drug. But I suspect that's how they want to push their products. They should consider how decades of availability of contraceptive drugs haven't done anything for the disempowered, nor much for fertility, either.

A second important issue around PrEP is that the HIV industry as a whole, that vast 'umbrella' of people and institutions who are doing very well out of the HIV pandemic and want to do a whole lot better, doesn't know a great deal about how HIV is transmitted. Or rather, much of their 'technology' is aimed at sexual transmission of HIV when non-sexual transmission of HIV is not talked about.

Joep and the string of competing interests he lists in his article have been trying to set the agenda for years, they are still trying. Opposition should come from anywhere there is a legitimate worry about the agenda for every international HIV/Aids conference, because the worries are many. Whereas the agenda of Big Pharma is always the same: how to get bigger.

Healthy people don't need medicine and sick people don't need useless, potentially harmful medicine. As long as there is Big Pharma, stupid ideas like PrEP and hyenas like Joep, I hope there will also be protests and protesters, shouting all the louder because they don't have access to the high platforms and the influential ears enjoyed by the HIV industry.

Welcome to Pre-Exposure Prophylaxis or PrEP

Preventing a disease may seem preferable to waiting until someone becomes infected and then treating them. But HIV pre-exposure prophylaxis (PrEP) is a bit different. In countries with high HIV prevalence, such as Swaziland, Lesotho, South Africa, Botswana, Zimbabwe and a number of others, so many people are at risk of being infected, the cost of providing medication for them all would be prohibitive. After all, PrEP is not a once off inoculation; it is something you need to take for as long as you are sexually active.

So why write a blog about that? Well, I have searched the web a good deal for information about PrEP and it is overwhelmingly positive and overwhelmingly shaped by the very people who stand to gain from promoting it, namely the pharmaceutical industries, Big Pharma. I would expect to find at least some articles that criticize or question or even try to analyze PrEP. But I only came across one. So I'll be on the lookout for others.

HIV is a virus spread by contaminated bodily fluids, such as blood, semen, vaginal fluid and others. It is relatively difficult to spread through sexual contact, especially penile-vaginal contact, though anal sex is especially dangerous. But some of the most common routes of infection could be non-sexual. In which case, it would be a waste of effort and money to target people on the basis of their assumed sexual behavior with PrEP. Unless you wanted to waste money; unless it isn't your money; unless it is development money.

If you want to hear cheers for PrEP, just have a look at the Aids Vaccine Advocacy Coalition (AVAC), a pharmaceutical poodle that yaps a lot but, ultimately, protects nothing but Big Pharma profits. It claims not to be supported by Big Pharma, but they do get money and support from institutions that cheer for little else: UNAIDS, CDC and IAVI. And then there's the Bill Gates Foundation, which makes a lot of money from Big Pharma and other, equally admirable, multinational interests.

I have written about PrEP elsewhere, especially on my HIV in Kenya blog (just search for 'PrEP' in the search box) and briefly in the blog, Kwa Sababu, now sadly defunct. But I think the field of PrEP is in serious need of analysis and discussion. I hope others feel the same way.