Is PrEP Destined to Be a Recreational Drug for Westerners?

There's a lot of excitement, not so surprising, about the results of a PrEP trial which took place among gay men and transgender women; it can cut new infections by at least 44%, those carrying out the research say. Thankfully, there are also cautioning voices, suggesting that there is a long way to go and that 44% in ideal conditions may not translate into 44% in non-trial conditions, the above article being one of the cautioning voices.

Presumably timed to coincide with World Aids Day on the 1st of December, this good news is likely to dominate the headlines for some time to come. I needn't go through the ins and outs of the trial, they are widely available. And there are even some good critiques that raise questions that need to be asked about an approach to a disease that depends entirely on some drugs.

Technologies such as antiretroviral treatment (ART) are great when they are used to prevent and treat a virus like HIV.But something that bothers me about HIV drugs is that the, arguably more important, objective of preventing HIV transmission by finding out what its determinants are and mitigating them has long gone out the window.

I have argued elsewhere that a significant amount of HIV transmission comes from unsafe medical practices. The WHO estimates a figure of 260,000, likely to be on the low side. No drug is required to prevent this so-called nosocomial (or iatrogenic) transmission of HIV. All that is required is good, affordable healthcare.

But there doesn't seem to be much appetite for providing people with what they really need. Single diseases have always had greater appeal and the exaggerated association of HIV transmission with sex continues to make it the biggest single recipient of health funding ever.

Sean Strub has an interesting article on post-exposure prophylaxis (PEP), antiretroviral drugs used after a suspected exposure to HIV has occurred. He has found that many people who should know about PEP don't. Although it has been widely available to healthcare workers in wealthier countries, and ostensibly in poor countries, it is not promoted widely enough among the many people who may face similar or even higher risks.

[For more information about PEP, have a look at the PEPnow site.]

I have talked to a lot of people in Kenya and Tanzania who should know about PEP but don't. This is inexcusable because PEP has been available for many years. But the fact that it is nowhere near as well known as it should be suggests to me that the current enthusiasm for PrEP is not because it could reduce and perhaps eventually eradicate the virus.

The fact that 'we' or 'science' or 'technology' can do something does not mean it will be done. 20% of deaths in under fives could be prevented by provision of clean water and sanitation, another 20% are caused by easily preventable and treatable respiratory infections. The vast majority of maternal deaths are also preventable.

Dare I suggest that developers of PrEP are more interested in the 'recreational' drug market? Something to reduce the risk of contracting HIV without the need for condoms or other precautions, perhaps?

Will People Use Condoms With Pre-Exposure Prophylaxis or Microbicides?

A trial of combined condom and diaphragm use found that, although condom use increased during the trial, it returned to pre-trial rates afterwards. A commentator notes "What happens after trials has always remained very much a mystery". This appears to be true, and it's very disturbing.

Trial conditions are very different from non-trial conditions. Strict protocols are observed, at least in theory, so one would expect behavior to be substantially different once the intervention in question moves into the field. Especially when the trials show that the intervention only produced a small or temporary change in behavior. But results may even be a mere artefact.

Results of trials of mass male circumcision, microbicides (such as the tenofovir based gel tested in the CAPRISA trial), pre-exposure prophylaxis, test and treat strategies and other approaches to HIV prevention, which depend on the possibility of influencing sexual behavior, all share the risk of being artefacts.

Ariane van der Straten was involved in the Methods for Improving Reproductive Health in Africa project. This showed that, in many areas, the interventions involving diaphragms and lubricant, in addition to condoms and counselling employed for the control group, resulted in slightly higher rates of HIV transmission. However, the differences were not statistically significant.

Van der Straten points out that "it is a challenge to use concurrent HIV prevention methods, particularly barrier methods". All the technical solutions mentioned above require people to continue using condoms, even after circumcision and/or using microbicides or taking pre-exposure prophylaxis. Does she mean 'it is a challenge' or 'it is probably inadvisable'?

The study emphasised an unmet need for birth control, but this is hardly a surprise.

Van der Straten's concluding remark is particularly related to one of the assumptions about microbicides, though it may apply equally to pre-exposure prophylaxis. That is the claim that they are 'female-controlled'. Van der Straten says "In the past we have been naive, thinking that female-controlled methods could be used independent of men's involvement, but it's difficult to use any of these methods secretly, so there is a need to involve male partners in female-controlled methods so that they support their partners".

The full report is also freely available online.

A Technical 'Solution' in Search of a Problem

In an article on self-testing for HIV in aidsmap.com:

"Dr Renee Ridzon of the Bill and Melinda Gates Foundation warns that self-testing is going to be necessary if antiretroviral-based prevention methods such as microbicides and pre-exposure prophylaxis become available, simply to accommodate the volume of regular testing that will be necessary to use these methods safely."

No surprise that the Foundation would be involved in anything to do with medicalization of health and the use of technical solutions in the absence of adequate health facilities, health personnel and even more general health (as opposed to disease) issues such as water and sanitation, air quality, living conditions, etc.

This sounds very much like a solution in search of a problem, a phenomenon that makes up a very significant proportion of Big Pharma sponsored health 'research' (the Foundation being an integral part of Big Pharma).

I've discussed this in more detail on my HIV in Kenya 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.

AVAC is Not an Advocacy Group, it's a Pharmaceutical Industry Front

There's a brief article about PrEP in Medical News Today that promises a rash of mentions in the near future. But the article refers to AVAC (AIDS Vaccine Advocacy Coalition) as a HIV prevention advocacy group.

AVAC is no such thing. It is a front group for the drug industry, especially those producing HIV related drugs. It advocates strategies that increase the use of and dependence on antiretroviral drugs, both for HIV positive people and HIV negative people. For AVAC, prevention means drugs, lots of them.

The article and comments by Mitchell Warren, director of AVAC, is from a longer article in the New York Times. The usual suspects are involved, Bill Gates and the Gates Foundation, the Ford Foundation, the International Aids Vaccine Initiative, UNAIDS, WHO, all big supporters of technical solutions and drug multinationals.

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.