Could PrEP be in Competition with Mass Male Circumcision Programs?

[Reposted from the Pre-Exposure Prophylaxis (PrEP) Blog]

After years of trying to create a market for pre-exposure prophylaxis (PrEP) pills, such as Truvada, Big Pharma has turned to their favorite mass marketing ploy: dumping their products in African countries that are starved of health funding. Of course, why wouldn't they dump them in Africa, won't they be paid for with donor funding?

An article in Kenya's The Star entitled "Kenya: 'Wonder Pill' for Risky Sex On the Way" takes the unusual step of raising some difficult questions about PrEP, rather than repeating the Big Pharma press release, despite a shaky introduction. The article continues "Kenyans involved in risky sex behaviours will soon get a 'wonder pill' that can prevent HIV infections. Experts say Truvada, which some call the 'new condom', can reduce chances of catching HIV but there are fears the drug may be misused by the youth".

What, exactly, would constitute misuse of the drug? If it can cut the risk of infection by "up to 75 per cent if one faithfully swallows it daily", what could go wrong? Well, as the article eventually reveals, most people don't swallow drugs daily and most people can not expect 'up to 75%' reduction in risk. That figure is not even from a randomized controlled trial, but from a 'sub-group' study, where the best results are used to exaggerate the level of protection people, in (comparatively) strict trial conditions, may expect. Outside of that sub-group, and outside of drug trial conditions, risk reduction is far lower.

It's odd that such reports talk about studies and proofs for something that they then refer to as a 'wonder pill', a 'new condom' and talk of 'up to 75% protection' (although that's a bit weak compared to the term 'invisible condom' used by those marketing mass male circumcision), and the like. These are PR buzzwords, not scientific findings.

It is said that PrEP programs intend identifying those most at risk of being infected, such as sex workers, intravenous drug users and men who have sex with men. This will be a departure from vilifying these already stigmatized and criminalized groups; it remains to be seen how much donor funding will actually be spent on these groups to provide them with PrEP, given that it has been so difficult in the past to provide them with condoms, injecting equipment and even basic sex and sexuality education.

As the article says, Truvada is expensive, and it has made billions of dollars for Gilead. So it's worth their while pushing as much of the stuff as possible in countries with high HIV prevalence while the patent guarantees that their product will face little competition. By the time the patent expires the likes of Bills Clinton and Gates will surely have set up some program whereby the drugs can continue to be purchased at inflated prices.

The article makes the important point that nearly 1 million HIV positive Kenyans currently need antiroviral drugs just to keep them alive. So why would donors want to provide these same drugs to people who are not yet infected with HIV (aside from an obvious desire to enrich big pharma)?

Oddly enough, a cost effectiveness study makes its estimates using existing levels of male circumcision and antiretroviral therapy. This means that the three multi-billion dollar programs will be in direct competition with each other for funding, and each one will be trying to claim that any drop in HIV incidence is a result of their work. The study also seems to assume far higher levels of success than have been achieved so far. But that's big pharma for you.

While Gilead and other pharmaceuticals can gain a lot from any increase in antiretroviral therapy and PrEP programs, they may not stand to gain from mass male circumcision programs. Their assumption that their PrEP programs will be cost effective only in countries where circumcision levels are low suggests that by the time their product may be approved, the circumcision programs will already need to have failed, some time around 2015.

Worries that people may use PrEP as a kind of recreational drug, so they can dispense with the use of condoms when they are engaging in sex with people who may face a high risk of being HIV positive are not very convincingly addressed; nor are worries that overuse and misuse of antiretrovirals, either for HIV positive people or as PrEP, are brushed aside, with remarks about "government policy" and making the drug available "in form of a package that probably includes HIV testing and other prevention methods".

I seem to remember condoms, circumcision, ABC and various other programs being made available in the form of a package, without that leading to extraordinary results. But it will be interesting to see if PrEP will erode some of the funding currently being made available to, or earmarked for, mass male circumcision programs.

Circumcision programs stand to rake in billions for the big providers, but widespread use of PrEP would be worth far more. It's unlikely that a full scale version of both programs could co-exist; they are not mutually exclusive, but their cost effectiveness is predicated on their being the only or the main program in high HIV prevalence countries.

Whether one program displaces another, or whether they all get funded, the losers will be people in high HIV prevalence African countries, which will continue to suffer from under-funded health and education sectors. They will continue to be a mere 'territory' for sales reps, who will continue to carve things up in ways that should be very familiar to us by now.

Is it Safe Yet to Come Out of the Condom?

Dr Joseph Sonnabend has an excellent critique of the iPrEx trial, the use of oral Truvada as pre-exposure prophylaxis (PrEP) against HIV. PrEP is the use of antiretroviral drugs in HIV negative people who are considered to be at high risk of infection. The trial achieved a 44% success rate, which is disappointing, but it's best to read Dr Sonnabend's critique if you're interested in a more balanced account of the trial than you'll find in the mainstream press or in the academic literature.

One of the many interesting points in the article, however, is not about PrEP, it's about HIV prevention interventions that aim to reduce HIV transmission by influencing people's sexual behavior. I have always objected to the view that HIV is almost entirely a result of 'unsafe' sexual behavior in African countries. So this means that I also feel a lot of behavioral interventions are not, despite claims to the contrary, contributing significantly to reductions in HIV transmission.

Dr Sonnabend argues that "If prevention education has been a failure, it’s not because it doesn’t work, but because we have not provided it well enough. There has been too little and most has not been properly targeted."

It's important to note that Dr Sonnabend is not writing about Africa, he is writing about a US, urban context. But what he says about behavioral interventions not being provided well enough is, I think, true of Africa too. And it is only now that PrEP is being bandied about as the solution to the HIV pandemic that others who promoted behavioral interventions in the past are beginning to question their effectiveness.

I am not opposed to behavioral interventions per se, I just haven't heard of any that have been particularly successful in reducing HIV transmission in Africa. But I think exercising some restraint over partner choice, number of partners, unprotected sex, age of sexual debut, unplanned pregnancy and many other things, is important. I also think these measures are important regardless of whether HIV is an issue.

However, in the African context, targeting could refer to two very different issues. The first issue in African countries with high HIV prevalence, I would argue, is not that some people have a lot of 'unsafe' sex but that many people are not being infected sexually. If people being infected sexually can be targeted and can be subjected to appropriate behavioral interventions, that should reduce sexual transmission of HIV.

But as things stand, with the assumption that most HIV is transmitted sexually, there is virtually no targeting. Everyone who has sex is considered to be at risk and anyone who is infected is considered to have engaged in 'unsafe' sex. This is despite plenty of evidence that non-sexual modes of HIV transmission are contributing significantly to African epidemics. Non-sexual modes of transmission need quite different types of intervention.

You might think that those most at risk of  sexually transmitted HIV, such as sex workers and men who have sex with men, would be targeted in African countries because of their levels of sexual exposure. This a second kind of targeting issue, but these groups are almost completely ignored by HIV programming. That's unless you count the self-righteous rhetoric, which needn't cost very much.

Also in relation to behavioral interventions, Dr Sonnabend makes an observation about condoms that is missing from any of the prevention literature I have seen:

"Condoms can be a barrier to intimacy which for many is the most essential aspect of sexual intercourse, for both receptive and insertive partners. So recommending the use of condoms without acknowledging the significant obstacle they may present to a fulfilling sexual experience is a real problem. Pleasure is part of that fulfilment and for some insertive partners condoms are a significant impediment to experiencing it."

Given that condoms are the best behavioral intervention we have got, we need to be realistic about their use, which is often low among those who may be most in need of them. The three hackneyed imperatives, those to abstain, be faithful and use a condom, could all be trumped by one of the most basic and sometimes the most intense of human desires, the desire for sexual intimacy. Perhaps imperatives delivered without any authority whatsoever achieve the opposite to their intended result.

One day, it may be possible to supplement behavioral interventions with PrEP, microbicides and vaccines. But even then, it will be human behavior that determines whether this successfully prevents HIV transmission. As the iPrEx trial has shown, if people don't take the pills, they won't work. Unfortunately, the trial hasn't yet shown that if people do take the pills they do work. There's still a lot to learn about human behavior when it comes to HIV prevention interventions. The question is, will what we learn continue to be ignored?

By the way, it is not safe yet.