Universal Access to Water Before Universal Access to PrEP

With the buzz that tends to be drummed up when a clinical trial is not, at least on the surface, a complete failure, it is easy to forget what things are like in countries with high HIV prevalence. IRIN has an article about health systems in Kenya needing an overhaul and the frequency of drug shortages and stock outs. Uganda, Tanzania and other countries have similar problems.

This is not just about drugs. On my other blog yesterday, I cited a systematic review of healthcare associated infections which noted "inadequate environmental hygienic conditions; poor infrastructure; insufficient equipment; understaffing; overcrowding; paucity of knowledge and application of basic infection-control measures; prolonged and inappropriate use of invasive devices and antibiotics; scarcity of local and national guidelines and policies [and] reuse of scarce resources, such as needles and gloves."

This is not just about HIV, either. People suffer from and die from preventable and curable diseases, conditions that are cheap and easy to prevent and cure. Many of these diseases relate to a complete lack of basic scientific, health and hygiene knowledge. Many relate to lack of basic rights, such as clean water and sanitation and a healthy environment.

Many people in East African countries have little or no access to health facilities and it's difficult to know how to view that problem. Because many are infected with various 'hospital acquired infections' (HAI) in health facilities, such as HIV, hepatitis, bacterial infections, urinary infections and numerous others. In fact, high rates of HIV are often correlated with relatively high access to health facilities. The lowest rates are often in places where people don't have access to health services.

Large scale rollout of antiretroviral drugs (ARV) has had mixed results, with many people continuing to die of preventable and treatable conditions, such as TB. The number of people on ARVs is quite a small proportion of those who need them. And countries with big programs are depending on donor funding, which is not guaranteed to get any higher, and may even drop.

So the questions are: will health systems be improved enough to make a better job of supplying the enormous number of people who would be in need of PrEP than has been done with ARVs? Where will all the money come from and will the problem of ARV rollout be solved at the same time? Will health issues other than HIV receive the attention they deserve or will people with needs that can be resolved cheaply and simply continue to be ignored?

PrEP is just a pill, it is not the means for ensuring that people who need it receive it and take it as prescribed for as long as they need it. That's no different from ARV treatment, either. But with ARVs, we know that a sustained program with a wide enough reach is still pretty elusive.

So why are we talking about PrEP as if it is anything more than a theory? Universal access to clean water and other basic rights should have been provided before ARVs, at least people would have something with which to swallow the pills. Otherwise, we're just tinkering with the problem.

Experts More Muted About iPrEx Results Than Media

The iPrEx trial tested truvada as an oral pre-exposure prophylaxis for men who have sex with men (MSM). The results were moderate, showing a 44% efficacy. The result would have been far higher had adherence been higher. But if adherence was something that could be assured, high and consistent rates of condom use would make PrEP irrelevant.

From what I can work out also, the study did not test the partners of those who became infected with HIV during the trial. This makes the claim that those taking the drug were protected from sexual transmission, as opposed to some kind of non-sexual transmission, somewhat tenuous. This question is crucial and is still hanging over the equally hyped CAPRISA 004 trial, which tested the use of 1% tenofovir as a vaginal gel.

As a result of very low adherence to the drugs in the iPrEx trial, it is not possible to claim with any confidence that resistance will not develop where those taking the drug become infected with HIV, but where the infection is not detected in time. Most of those who seroconverted were not following adherence advice. HIV strains resistant to truvada were detected in two participants who entered the trial with HIV infection that was not detected until later.

The issue of how early HIV infection is detected in people taking PrEP is very important. How regular would testing need to be for the threat of resistance to be minimized? Most people never get tested. Some test once in their life. Very few test regularly. Would quarterly, or even yearly testing ever be logistically feasible or affordable?

Resistance is not just a danger for the person taking PrEP; resistant strains of HIV can be transmitted, perhaps even to people taking the same PrEP formulation. Worse still, resistant strains could infect large numbers in certain sexual networks, for example, where MSM are targeted as an especially high risk group.

Whatever about the use of this drug in rich countries, the feasibility of using it in developing countries seems pretty low. Levels of side effects were not high, but that's not so comforting given that adherence was so low. The drug itself is very expensive but the cost of regular testing of millions of people, even the very possibility of such an undertaking, makes it a luxury that few could afford. Dropping the price of the drug will not make the cost of large scale rollout of PrEP any more affordable.

Interestingly, it is reported in the appendix that rates of receptive intercourse dropped sharply in the first 12 weeks and stayed at about half what they were at the start. Use of condoms during receptive intercourse increased to a high level, also during the first 12 weeks, and stayed high for the rest of the trial. Similar patterns of protective behavior were noted in the CAPRISA 004 trial.

These findings suggest that even people thought to be at high risk of contracting HIV are amenable to taking precautions. Sadly, rollout of PrEP is not expected to include rollout of similar levels of support and monitoring found in clinical trials. But most sexually active people in some African countries seem to be at high risk of HIV infection and health facilities are unable to contain the endemic chest and diarrheal conditions that kill so many, let alone HIV.

Dr Joseph Sonnabend has a good critique of iPrEx which is worth reading in its entirety. It seems as if those who want to latch on to anything that can be dressed up as good news are being allowed free rein to do so. But those who treat the issue more thoughtfully, and that includes those involved in the trial, don't seem to be shouting from the rooftops.

In the Absence of Promiscuity, PrEP is Useless

An IRIN article ends with a comment from Dr Helen Rees: "I'd ask why we're doing these studies in these countries at all if we're not going to implement any of these interventions,...I find that unethical." What I find unethical is that these interventions all assume that HIV is primarily transmitted sexually, despite evidence to the contrary.

However, these drug trials have shown one very significant thing: most African people don't have sex a great deal. Their sexual behavior is not extraordinary. And Modes of Transmission Surveys for Kenya and Uganda show that it is ordinary people in long term monogamous relationships that contribute the vast majority of HIV infections in those countries. And yet HIV transmission rates are extraordinarily high.

If you had unlimited amounts of money, you could unleash PrEP on whole populations. It would be a stupid and dangerous thing to do, but if you think, as the HIV mainstream do, that most Africans have enormous amounts of high risk sex all the time, you might think it would be worthwhile.

But there isn't even enough money to supply half of the people globally in need of antrietroviral (ARV) drugs with treatment. The majority of people globally have never been tested for HIV. The majority of HIV positive people globally don't know their status. And PrEP would require that everyone, or most people, be tested as much as four times a year.

PrEP advocates need to get things in perspective. We know a lot less about HIV transmission than we should, given the amount of study that has been done over the years. We are not in a position to consider HIV prevention programs that involve vastly higher numbers of people (and finance) than current programs, which are struggling, despite claims to the contrary.

It's a sobering thought that HIV transmission rates are still very high in countries with very large ARV programs. Also, death rates are very high among people on treatment. People are dying, not because they are HIV positive or because they have AIDS, but because they have preventable and treatable conditions that are just not being treated.

Developing countries with high HIV prevalence have low levels of education, health, infrastructure and many other factors that are intimately related to rapid HIV transmission. Churning out drugs in ever increasing quantities is not going to change things much, especially if evidence that HIV is not primarily sexually transmitted continues to be ignored.

What we are ethically obliged to do is to be frank and honest about sexual transmission of HIV: we don't know why transmission rates are hundreds of times higher in some parts of some African countries than they are in most countries, developed and undeveloped. Therefore, we cannot continue to base most prevention programs on the assumption that Africans have superhuman amounts of sex.

PrEP may turn out to have some use but we have, as yet, no idea what that would be.

[For more on the false hypothesis about African promiscuity, see my other blog.]

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.

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.

Are Healthy People More Likely to Take Drugs than Unhealthy People?

Loss to follow up is a common problem with HIV treatment programs and up to 40% of East Africans may cease to collect their drugs at some time. They may have gone somewhere else or died, but it's hard to tell. Records are not always well kept.

It's hard to know how good people will be at taking drugs to prevent HIV, as opposed to those that treat HIV. Early papers on adherence seemed keen to report good news, that people in developing countries were even likely to be better at keeping to treatment regimes than people in rich countries. But later papers have not always been so optimistic.

I have seen several mentions recently of people preferring to pray and believe that God will save them, keep them alive, 'cure' them of HIV, etc. People who believe this don't always stop their treatment, although some do. But even temporary lapses in taking antiretroviral drugs can cause problems such as opportunistic illnesses and resistance build up.

I have even come across people who have insisted that praying is the best response because God will decide, whatever the outcome is. This is disturbing to witness, especially when one suspects that many people taking this view also seem to associate HIV with some kind of evil or sin.

A recent article suggests that some young people in Uganda are being persuaded to give up taking Aids drugs and relying on their beliefs instead. Some of those persuading them are possibly not even genuine pastors, though it seems equally inexcusible whether they are genuine or not.

Proponents of PrEP tend to ignore the potential problems of ensuring that people who are not sick take drugs as required in order to prevent infection with HIV. Especially as research into exactly how most HIV is transmitted in high prevalence countries is thin on the ground.

Never Mind Efficacy, Think of the Profits

There's an interesting article in the Emerging Health Threats Forum about bird flu behavior change campaigns and people's perception of risk. It was found that "People who witness avian flu outbreaks in animals near them fear the disease less than those with no experience of it".

Most HIV prevention campaigns have attempted to influence people's sexual behavior by warning them about certain risks and telling them how to avoid them. Some of these campaigns have been assessed and the results tend to show that many people continue with the behaviors considered to be risky.

Speculation has suggested that HIV transmission rates in Uganda, and eventually in some other countries, started to decline once people realized that many of those around them were becoming sick and dying. This is unlikely to be true because high death rates would have occurred some years after declines in transmission started.

However, much HIV prevention work continues with the assumption that people will modify risky behavior once they know that it is risky and what steps they can take to ensure that they don't become infected. And perhaps the assumption is, to some extent useful. Perhaps people will eventually begin to take precautions and the bulk of sexual transmission of HIV will be eradicated.

Wide availability of PrEP in high HIV prevalence countries may become a 'protective' behavior, something people who cannot avoid sexual risks can take to reduce the risk of infection. In textbook cases, where HIV transmission really does occur because people are taking unnecessary and avoidable sexual risks, PrEP may even have a substantial effect on sexual transmission.

Unfortunately, a good deal of sexual transmission is probably not of the textbook variety. The incredibly high rates of risky sexual behavior attributed to Africans in the textbooks are more likely to be a widely shared fantasy, stubbornly held by those who are in the best position to see how such views are completely without foundation.

But even where PrEP is available to prevent some sexual HIV transmission, it is unlikely to have any impact on non-sexual HIV transmission. The fact that UNAIDS and other institutions are not even targeting non-sexual transmission doesn't help, but giving out pills, to however many people, is not the most expeditious means of reducing, for example, health care related exposure to HIV.

It is not a new discovery that behavior and behavior change are complicated and difficult to effect. And this is not to say that some kinds of behavior change shouldn't be attempted and facilitated. However, concentrating all our attention on sexual HIV transmission, without even attempting to find out how much of the virus is spread though non-sexual modes, results in an unknown level of avoidable infection.

PrEP may hold some promise for certain kinds of sexually transmitted HIV but it will not eradicate the virus. And it will have little or no impact on non-sexual transmission, which is probably responsible for a large proportion of the highest prevalence epidemics, all of which are found in a handful of sub-Saharan African countries.

Some advocates of PrEP may truly believe that it could eventually play a part, perhaps a big part, in eradicating the virus. People who believe this don't know very much about HIV. But I suspect that PrEP is just a clever way of increasing HIV drug sales by several hundred percent, perhaps even several thousand percent.

Having a ready supply of trial participants in countries where the virus is common will help a lot in getting the drugs on the market. Meanwhile, epidemics in African countries continue on trajectories that are completely independent of any HIV prevention programs that have taken place so far.

Some Disturbing Considerations Relating to PrEP Trials

I’m not sure why Aegis have an article about PrEP entitled ‘hope and excitement greet first successful microbicide’ so soon after worries being raised that the money to do further required tests has not been forthcoming. These refer to the CAPRISA 004 trial, which received the most hype during the Vienna AIDS Conference only a few months ago.

Anyhow, the article notes that “Behavioural messages that encourage abstinence, monogamy and use of condoms have had […] only a limited long-term impact on the spread of HIV in that region.” The article calls for HIV prevention strategies to be made relevant, though they are not talking about making them relevant to the possibility that some HIV is not sexually transmitted.

A popular claim about PrEP (and other technological fixes) is that they can be applied by women and are “under their control”. There may be some truth in this. Yet, oral contraception has long been available without most women choosing to avail of it. Many instead opt for injectable versions, thus putting themselves at higher risk of being infected with HIV and other viruses as a result of unhygienic health practices.

Injectable versions of contraception are very popular with married women and sex workers, though perhaps for different reasons. Married women say they are not willing to risk having their husband interfere if they keep oral contraceptives at home, which they have to take regularly. It remains to be seen whether attitudes towards PrEP gel are any different. Is it really ‘under the control of women’?

The question is pertinent because unsafe health care practices are not under any clients control, whether male or female. People might be able to take precautions but they have to know that such practices could lead to infection and they have to know what they can do to protect themselves. The HIV/AIDS industry, in this instance, doesn’t seem to be interested in the strategy being under the control of those who face the risks.

The CAPRISA 004 trial, despite widely repeated claims, did not establish what risks were reduced among those taking part. Was it just the risk of sexual transmission that was reduced or was it also the risk of non-sexual transmission? The difference is crucial.

The article notes that the trial results were not affected by frequency of sex. But sexual activity was not very high during the trial and it decreased over time, as did use of the Tenofovir gel. However, HIV transmission over the course of the trial was extremely high, even among the intervention group.

It is also noted that “average viral load was not significantly different” between the intervention and control groups. The ‘Test and Treat’ strategy, which was being hyped as much as PrEP two years ago, claims that placing every HIV positive person on antiretroviral drugs will reduce viral load and therefore reduce transmission. But there is now evidence that low viral load may not be so closely related to rates of HIV transmission, something I have recently discussed on my other blog, HIV in Kenya.

The Aegis article warns that the results need to be viewed with caution; this can not be stressed enough. These trials, CAPRISA 004 in particular, seem to take little notice of how HIV might be transmitted among the populations taking part in their research. If HIV is not all transmitted sexually, such trials will continue to produce invalid results and people will continue to be exposed unnecessarily to the risk of infection with HIV and other blood-borne viruses.

Big Pharma Predicts PrEP Will Be Great, For Them

There's always a lot of talking up programs that cost heaps of money, never so much reflection on why throwing money at a problem (or at an industry) doesn't have the predicted effect. So it's surprising that an article by the BBC admits that the target to provide everyone who needs antiretroviral drugs (ARV) with them by 2010 has been missed. Only a third of those who need the drugs are receiving them, according to official figures (WHO, UNAIDS, etc).

There's a bit of hedging because WHO guidelines concerning the stage at which people need ARVs has changed, so the overall figure has gone up. But the target would have been missed, regardless. The figures sound very impressive, but it's hard to find a clear statement of how many people have received ARVs and whose supply has, for some reason, been cut off, how many are lost to follow up, how many have died or are not responding to treatment, how many are in need of second line drugs because they have developed resistance to first line treatment, how many are receiving second line drugs, etc.

For instance, some countries highlight incidents where money or drugs are going missing, but it's rarely made clear what impact that has on treatment or HIV transmission. And while articles constantly make statements such as "virtual elimination of mother-to-child transmission of the virus by 2015 is possible", other articles make it quite clear that there is a huge gap between optimistic press releases and what's happening on the ground. Only 24% of Ugandan children who need them are receiving ARVs, 150,000 are living with HIV, nearly 15,000 are born with the virus every year and 16,000 dye of AIDS every year. And Uganda has received far more money, and far more attention, than most other African countries.

It's good to hear that some pressure is being applied to countries with high HIV prevalence to make some of their own revenue available for the epidemic, and perhaps for health as a whole. So far, most of the money for ARV programs has come from external donors, but their funds are drying up. However, given the progress of attempting to put millions of sick people on drugs, how would a program that aims to put far higher numbers of healthy people on drugs fare?

Pharmaceutical Research; Blink and You've Missed it

Only last year, a Cochrane Review of PrEP concluded that "there is no reliable evidence to support the use of any antiretroviral agent for HIV chemoprophylaxis". At the time the study was carried out, only one study met their inclusion criteria and the result of it was not statistically significant.

But it's amazing how much can be achieved in a short time by a multi-billion dollar multinational pharmaceutical industry with ample funding and a high probability of huge profits. Ever since the HIV industry has changed its tune from 'The news is bad, we need more money' to 'The news is good, we need more money', there has been lots of favorable writing about PrEP and related uses of HIV drugs.

The Cochrane Review listed the following implications:

"We advocate well-conducted trials with the statistical power to answer questions about the value of PrEP in preventing HIV infection in various populations and risk groups. Ongoing and future trials should evaluate other important issues, such as behavioural disinhibition and drug resistance, which are some of the major concerns about the use of chemoprophylaxis for HIV."

And already there have been trials which are being interpreted in the most generous terms possible; there have been papers about how disinhibition is not likely to be such a big problem; and even drug resistance is being written about as if it is a mere challenge, not a danger, like drug resistance in relation to other diseases.

This is amazing progress, truly amazing. I'm simply amazed.

Good Cop, Bad Cop, No Cop, No Problem

A recent article on PrEP notes, among other things, the problem of 'addressing informal markets'. The article is entitled 'Implementation Science of Pre-exposure Prophylaxis: Preparing for Public Use' and it lists many of the 'challenges' of PrEP, which is useful. But because there are so many challenges, informal markets only get a brief paragraph.

If people are getting drugs for free, they could easily sell them on. If PrEP is intended to be sold to people, the drugs that are currently free can be sold, instead. This is an informal market.

This development of informal markets has occurred at various times in various places. There is evidence that it still occurs, which is not really a problem for the pharmaceutical industry, as long as they are getting paid. But it is a problem that people could end up taking unprescribed drugs and using them for purposes for which they were not intended.

There is also a danger that, as the drug taking will not be monitored, if the person becomes infected with HIV, resistance could develop. Again, this is not a problem for the pharmaceutical industry because they have other, more expensive drugs that they can sell. But the person selling on the drugs could be failing to adhere to their own regime and those receiving the drugs are in danger of developing resistance and even passing that on to others.

If PrEP is to be rolled out as a possible means of preventing HIV transmission, it would want to be very well controlled. The numbers of people involved would be far higher than the numbers currently on antiretroviral drugs (ARV) and this program is not very well controlled. As much as 25-40% of people on ARVs in countries such as Kenya could be lost to follow-up. They just don't have the record keeping capacity in their health services to administrate current levels of ARV roll out, let alone an even bigger roll out of PrEP.

Also, the phrase 'implementation science' in the article title smacks of 'scientists' doing more than a little work to help pharmaceutical companies push their wares on populations who may be very reluctant to buy them if they actually get to know anything about them. Implementation science may or may not be related to the practice of 'medical ghostwriting', where pharmaceutical companies (or people acting for them) write up their 'research' and then get some bona fide scientists to put their name to the paper. How much this happens with regard to PrEP, I couldn't say.

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.