Give ARVs To Those Who Need Them; PrEP Can Wait

It's been a while since I've written anything about PrEP and it's hard to keep up with two blogs. But there have been a few articles on the subject. One, and I've only seen the abstract, finds that PrEP has high acceptability but that adherence and use are more challenging. This may be a reflection of the sheer idiocy of throwing drugs at a disease that is treated in almost complete isolation from all other diseases, from the conditions in which people live, from their overall health status, etc.

Interestingly, people on PrEP ran the risk of being perceived as HIV positive, giving rise to stigma, rumors and relationship difficulties. A paper about lymphatic filariasis reports that people have difficulty understanding why they should take pills for a condition for which they have no symptoms, and also why they should take the same pills for what they see as two different conditions (swollen legs and swollen testicles).

The authors of the PrEP article note that "adherence was challenged by complexities of daily life, in particular post-coital dosing adherence suffered from alcohol use around time of sex, mobile populations, and transactional sex work". The research into giving antiretroviral drugs to HIV negative people took place in Kenya, a country where many HIV positive people with a critical need for the drugs are not receiving them, and where many babies are still being infected by their mothers (or perhaps through some other route that antiretroviral drugs will not be able to address, such as through unsafe healthcare).

A review of a mathematical modelling study of PrEP mentions the ethical problems of rolling out such a program in a country where many HIV positive people are not yet on antiretrovirals. The article finds that the strategy would be cost effective in a middle income country, such as Peru, but only if it was highly targeted. However, this is where PrEP and most other HIV interventions come unstuck in African countries. HIV in high prevalence African countries is characterized by not disproportionately affecting just a few easily identifiable groups. While prevalence is high in certain groups, the largest groups of HIV positive people don't have obvious sexual risks that could easily be targeted. Also, these groups are far too large for any African country to afford.

What I don't really understand about PrEP though, is why it is necessary at all. Proponents of the use of antiretroviral drugs in as many scenarios as possible (early treatment, lifetime treatment for women receiving prevention of mother to child treatment, etc) tell us that someone on ARVs is not very infectious. If PrEP could be targeted at people who are thought to be at risk, targeting those who put them at risk would seem like a much better prospect; that is, targeting people who are already HIV positive. They are a far smaller group, for a start, and this would be a good reason for putting all HIV positive people on ARVs as soon as they have a clear clinical need for them.

PrEP is Win-Win for Big Pharma, Lose-Lose for Ordinary People

When a PrEP trial produces poor results, the reaction is often to point the finger at the patient: they didn't take the drugs regularly, 'adherence' was low, etc. The irony of this is that people thought of as good candidates for PrEP are often those who have not successfully modified their sexual behavior, or have shown themselves unwilling to do so. If they will not or can not modify their sexual behavior, why would they be more willing or able to modify their drug taking behavior?

Some drug trial reports parcel up the high achievers and exclude the low and medium achievers and call it a 'sub-study' or something similar. But the point of a randomized controlled trial is to make it clear what kind of result can be expected of people taking part, not what kind of result can be expected if everyone behaved as drug manufacturers would wish them to. Given that people don't behave in real life as they do during drug trials, the results for strategies such as PrEP so far have been somewhat encouraging, but not good enough to roll out the strategy.

Even with PrEP, people are encouraged to engage in safe sex, to limit their number of partners, to use condoms, etc. If they can't or won't do some or all of those things, PrEP will not be very effective; but it may not have any positive impact at all. Those behind the trials and those producing the drugs are anxious to portray the strategy as tested and proven, but it is most definitely not, not yet anyhow. One of the main exponents of the strategy tries to persuade us that PrEP is the way to go, but some of his readers are clearly not convinced. And the opposing case raises additional concerns about PrEP, referring to the strategy as 'grasping at straws'.

In countries where HIV prevalence is very high and transmission is highest among low (sexual) risk groups, those engaging in heterosexual sex with one HIV negative partner, PrEP is not going to be feasible. Those who face the lowest risk, but are paradoxically the highest risk group in Modes of Transmission Surveys, are unlikely to be targeted by a PrEP campaign.

And given that the majority of HIV positive people in need of treatment are still not receiving it due to cost, infrastructure, political and other reasons, it would be odd to offer the same drugs to people who are still HIV negative. It would seem far better to establish what exactly the risks are and address those risks before throwing yet more drugs at the problem. But PrEP is the way to go if you want to sell lots of drugs to healthy people; if that doesn't work, you'll then have lots of sick people to sell even more drugs to.

Truvada Manufacturer Gilead Stops Funding to Critics

The Aids Healthcare Foundation (AHF) provides healthcare for HIV positive people and advocacy in the broader field of HIV health. In that capacity, the AHF has criticized the pharmaceutical company Gilead Sciences on a number of issues, including drug pricing policies.

But in addition, AHF has questioned the use of Gilead's Truvada as a pre-exposure prophylaxis (PrEP), a pill to be taken by HIV negative people to give them some protection from HIV infection. It could be taken, for example, by someone whose sexual partner is HIV positive. However, PrEP is not as effective as using a condom and it doesn't protect against other sexually transmitted infections.

More importantly, using a drug like Truvada can give rise to the development of drug resistant strains of HIV, especially in users who are unknowingly infected when they start taking the drug or who unknowingly become infected while taking it. AHF have argued that every time someone gets a prescription for Truvada, they should also be able to show that they have been tested for HIV and the result is negative.

Drug manufacturers are not known for their tolerance of public accountability; as a result of AHFs actions, Gilead have stopped their funding to AHF. This is particularly unfortunate right now because approval for Truvada as PrEP, which was expected to be rushed through the usual regulatory procedures, has now been delayed so that the requirement for a negative HIV test be stipulated. But it's likely that Gilead will continue to lobby for the right to aggressively pursue their own ends at the expense of public health.

The increasing dependence on drugs with outrageously high prices is worrying even in a wealthy country like the US. But as the country has the highest HIV prevalence in the Western world, it would be an even bigger threat to the country's public health systems if widespread resistance to Truvada were to develop. As well as resistance developing in an individual taking the drug, resistant strains of HIV can also be transmitted to others.

Also of concern is that, up until now, HIV drugs have been used by HIV positive people. The use of the same drugs by people who are HIV negative should be raising questions in people's minds about how far public health should go with what is effectively medical treatment for perfectly healthy people.

They may even ask how far it is possible for public health to go; the number of healthy people should, hopefully, far outnumber the number of sick people; it's undoubtedly a great market. But some level of drug resistance is inevitable. So are companies like Gilead stealthily creating new markets for even more costly second line drugs by vastly increasing the number of healthy people taking Truvada?

Experts Unambiguously Opposed to Saying the Wrong Thing

Apologies for the lack of posting this year but I have had enough work keeping my other blog going. The subject of PrEP and related issues do also crop up there, though.

Daily use of Truvada has been backed for pre-exposure prophylaxis use by a panel of 'experts', which generally refers to people who are so well paid to say the right thing that no one else will disagree with them. It's likely that this use of the drug will soon be approved by the FDA. I wasn't able to find a register of the 'experts'' interests but I'm sure it would make interesting reading.

If approved, the drug will be prescribed for HIV negative people who are thought to be at high risk of being infected sexually, which generally refers to men who have sex with men in Western countries. The drug is not being considered for use by intravenous drug users. It is also unlikely to be of much value for commercial sex workers in wealthy countries as they are rarely infected unless they are also intravenous drug users or face other serious risks.

This suggests that PrEP is unlikely to be effective in high HIV prevalence developing countries, where high risk groups are not easy to identify. In many African countries, the bulk of infections among adults occur in married people and those in long term relationships, who don't face very high sexual risks. In other words, the drug is of little use as PrEP where it is most needed. But I'm sure that won't stop Big Pharma from lobbying the right people so that the potential tens or hundreds of millions of Africans can be exploited.

The process of palming off useless but extremely expensive drugs with potentially dangerous side-effects on Africans has been eased by years of publicity for the dominant HIV transmission paradigm, which says that almost all HIV in African countries is transmitted through heterosexual behavior. The fact that the paradigm is seriously challenged by empirical data has done little to influence policy, which concentrates on the politician, religious leader and media friendly process of wagging fingers, pointing fingers and poking fingers into the many HIV fuding pies.

Opposition from groups who claim to represent the interests of HIV positive people has almost all been taken care of in the time honored fashion of paying off anyone who speaks out of turn (or rubbishing anyone who won't take payment). A rare voice of dissent comes from the Aids Healthcare Foundation, which has consistently opposed the current trend of rushing into practices which have little empirical backing, but which mysteriously receive full backing from 'experts'.

Pharmaceutical front group Aids Vaccine Advocacy Coalition (AVAC), predictably, blow the trumpet for PrEP; pharmaceutical products ostensibly produced to treat illness would never have become as profitable if they were only used by sick people. But the UK's Nick Partridge puts his finger on the problem, probably inadvertently: "But we need to know if people at highest risk of infection are prepared to take a pill every day and whether there would be an increase in risk-taking behaviour which could outweigh the prevention effectiveness of Truvada."

The truth is, we don't know who is at highest risk in high prevalence countries, we know that most will not take the pill every day and it's very likely there will be an increase in risk-taking behavior, especially where people opt for PrEP because they know (or even think) they are at risk.


[For more about non-sexual HIV transmission and male circumcision, see the Don't Get Stuck With HIV site.]

Tenofovir Products in Search of a Market

A few days ago, an article appeared on AidsMeds.com about the drug Tenofovir being associated with an increased risk of irreversible kidney disease, which does not reverse even when the drug is no longer taken. Tenofovir is one of the main ingredients in a vaginal gel developed to reduce the transmission of HIV, although a recent trial was stopped early because the gel was found to be ineffective. Another trial of Tenofovir taken orally as pre-exposure prophylaxis was also stopped early as it was clear it would not be possible to demonstrate a difference in effect between the drug and a placebo.

Despite these findings, Poz.com reports that the US Food and Drug Administration (FDA) has accepted an application from the makers of Tenofovir, Gilead Sciences, to give a priority review of the use of the drug, in combination with emtricitabine, to be marketed as Truvada. Despite some less favorable findings about Tenofovir, the more favorable findings led to immediate calls for application for use as PrEP to be fast-tracked.

In addition to the above worries about Tenofovir, widespread use of PrEP is also likely to give rise to drops in use of condoms. This possibility is denied vigorously by defenders of PrEP, and some data has been produced to support that defence. But like male circumcision and the hormonal contraceptive Depo Provera, people tend not to think about dual protection against both HIV and unplanned pregnancy.

Interestingly, while injectable versions of Depo Provera and similar methods are said to be 'female controlled' relative to the oral version, this objection doesn't appear to be used or alluded to by proponents of PrEP or vaginal gel.

A paper has been published discussing these diverging trial results and the authors pay particular attention to adherence to the drug regime, which needs to be very high. The authors mention identifying "optimal populations for PrEP"; but they may find that these populations are least likely to need the drug. It's all beginning to sound like a product in search of a market; but where would Big Pharma be if it never took that approach?

Apologies for Lack of Posting

It's been some time since I have been able to write a post for this blog but I will get back to it as soon as possible. I also write about the lunacy of prohibitively expensive and purely technical approaches to what are public health and development issues on my HIV in Kenya blog and also on the Don't Get Stuck With HIV blog and website.