In spite of the bitter Christmas Day cold boding the snow storm that would sweep the area the following day, Mike Youle rolls up his sleeve to reveal the striking tattoo extending from just above his wrist to just below his elbow. It is his full name - M-i-c-h-a-e-l - in bold, blue-black Hebrew letters.
We are sitting on the garden terrace of the cottage where he is staying on his current visit to the Holy Land, the home of his Israeli-born boyfriend's parents in Mevaseret Zion. Youle, 46, is not Jewish, but the fact that it is December 25, and there isn't a Santa or a yule log in sight, doesn't bother him in the least. On the contrary, he says, he is happy to be missing the holiday hubbub back in Britain, from where he hails.
Director of HIV clinical research at the Royal Free Centre for HIV Medicine in London, and honorary senior lecturer in public health and general medicine at the Royal Free and University College Medical School, Youle is both a passionate professional promoting Pre-Exposure Chemoprophylaxis (PREP) as a strategy for dealing with the AIDS virus, and a gay man who - as someone not yet infected - hopes to benefit from it in his lifetime.
"Not that vaccine development isn't important," he says, explaining the nuances in the controversy surrounding HIV research. "But at 46, I will die before there's a vaccine for HIV. All vaccinologists agree. But, of course, they can't say that."
As unflinchingly candid as Youle is about gay sex in general and his own in particular, he is extremely careful when it comes to criticizing organizations which fund AIDS research, prominent among them the Bill and Melinda Gates Foundation. "Last year, $400 million-$500 million was spent on HIV vaccine development," he claims cautiously, clearly not wanting to bite the hand that feeds him. "[But] the cost of doing a study of the kind I am suggesting is $25m.-$30m. It's peanuts!"
In an hour-long interview, during which he speaks fast and fluidly, as if to try to get in as much information as possible, Youle explains why he believes that studies first "should be done among urbanized gay men" - the group infected at the fastest rate - "and only and in parallel, or afterward, much larger studies could be done among heterosexuals in [other] appropriate settings," such as Africa, "to provide the answer of whether [the results] are transferable [elsewhere]."
Your work has been aiming at prophylaxis, rather than vaccines, as a strategy to prevent HIV. How did you come to focus your research energies on PREP?
It began when I read a book by Henry Hobhouse called The Seeds of Change about how crops such as potatoes, cocaine and tea have changed society. The first chapter is about quinine. Prior to quinine's being available, the Gold Coast was really the Dead Coast, because white men couldn't go there without the risk of dying from malaria. Quinine enabled people who were not naturally protected from the disease to enter the area with some protection.
Now, we don't have a vaccine for malaria, but if I go to, say, Ghana or Congo in 2007, I still will take a modern equivalent to quinine as a pre-exposure prophylaxis. In other words, this is a model [to emulate for protecting oneself against HIV].
I'll get to the issue of vaccines later...
Today, the treatment for HIV is very effective. So now what tends to be focused on is whether infected people can get access to medication and, more importantly, to health-care workers who know what they're doing. If you don't have the trained doctors, nurses and pharmacists, it's a bit like giving me a brand new car... well, it will work for a little while, but as soon as it breaks down, I won't know what to do with it.
Take South Africa, for example, where 30 percent of the population has HIV. A high proportion of those are among the educated classes. Preceding that, there was the "brain drain" caused by political issues, in addition to emigration due to economic reasons. So what you find is many [African] countries now have very few teachers, doctors, nurses, etc.
So much for those who are already infected. But then there's the issue of those who haven't yet gotten infected. There has been a huge body of research on vaccines and microbicides - surface protectants, usually in gel or cream form. The difficulty with these is you're not going to be protecting somebody from contracting HIV orally - which we know is now 5 percent of acquisition - or anally. And whoever tells me that women in Africa don't have anal sex is not reading the literature.
There's also been a great deal of hype surrounding a series of studies on circumcision. A couple of years ago, young men in Africa were randomly allocated to be circumcised. This was done because of the finding that the epidemic has been largely sparing those areas where men are circumcised. Then, a couple of weeks ago, the studies in Uganda and Kenya were stopped, because they showed such a good reduction [of HIV] among the group who had been circumcised.
Does this mean that Jewish men are statistically less susceptible to AIDS than others?
Circumcision protects you if you're a man, because you have a smaller amount of foreskin to get damaged and infected. It therefore probably reduces the transmission to women who don't use condoms.
Does it not reduce the transmission to other men?
Well, no. It's complicated...
What about HIV in women?
One of the problems for women is highlighted by the case of Mexico, where there were a lot of heterosexual women - who were Catholic and essentially monogamous - turning up with HIV. Their husbands had been going off and having homosexual sex or sex with other women and coming back and infecting their wives...
Still, we had to ask why HIV was affecting gay men more than heterosexuals. The answer is that among gay men there's far more partner exchange.
Why wouldn't you simply recommend, then, that everybody use condoms and some kind of microbicide gel?
Certainly, up until now the use of condoms has really changed the epidemic. But, of course, people don't use condoms; we don't like them. One interesting development since the advent of effective therapy has been the concept of two HIV positive or HIV negative partners having sex without condoms. One new issue is how to deal with that, both sociopolitically and scientifically. Because someone with a resistant virus could transmit it to his sexual partner [who has a different strain].
It is potentially dangerous, then, for two infected people to have unprotected sex?
In theory, yes. In practice, it is less certain. There have been a number of cases of people getting two viruses over a short period. One question is: Are you protected by your body's immune response over time to the first virus? The second is: If you take antiretrovirals, are you prophylaxing yourself against getting a second virus?
So, this is one area in which PREP - albeit in people who are already infected - has potentially got a model.
Going back to the condom and microbicide issue, here is an example of why it is problematic: In the 1980s, a chemical called nonoxynol-9 was being used on condoms in gel form for gay men. Subsequently, there was a study in women showing that it actually increased the risk of transmission, because although it killed the virus, it inflamed the tissues, making them more susceptible to contracting the infection.
Other microbicides have emerged since then, but regulating them is problematic. And after the nonoxynol-9 story the American Food and Drug Administration has been quite slow to allow the development of research in that area. There was also a lack of money - until [Microsoft founder and chairman] Bill Gates came along.
Gates is giving a lot of money to AIDS research?
He is, and it's interesting what his organization will and will not fund.
The stated aim [of the Bill and Melinda Gates Foundation] is to support the development of therapies and care for the developing world - particularly for women and children. This may sometimes cloud their view of how best to do things. In 2001, I attended a conference on AIDS in Seattle. During a Q&A session with Gates, I got up and said: "I'm HIV negative. If I'm having sex with my HIV positive boyfriend (my boyfriend at that time was positive), should I take anti-HIV drugs to protect myself, in the same way that we take anti-malarials?"
Gates responded: "But you should be using condoms anyway."
And I said, "Yes, I would be. But, in addition, if the condom breaks, would it give me extra protection?"
So he asked, "Are there any drugs available?"
I named a few that were in use at the time, some of which were and still are pretty safe drugs. But it's always a balance between safety and efficacy, and once you move into an uninfected population, the hurdle for safety is so much higher. When we were dealing with people who were dying of HIV, we used to give them everything and anything - out of desperation. [But now], with each drug that emerges, the safety level has to be higher.
You refer to people dying of HIV in the past tense. This suggests a tragically ironic situation: Instead of dying out, those infected are continuing to have sex - which would indicate that as you're curing AIDS, you're also spreading it. Is that correct?
Absolutely. And there are studies indicating that the mass treatment of people with HIV will reduce transmission and the size of the epidemic. It is a totally curable condition in the same way that smallpox was.
Anyway, a few months after that [exchange with Bill Gates], his foundation gave something like $20 million to Family Health International and a group of other people to conduct pre-exposure prophylaxis studies, a number of which have been done. But there's a problem with them, because such studies have to be powered statistically to answer the [necessary] questions. Currently, a sample size of 6,000-8,000 people would be required for this. The sample could be taken from a certain country; it could be taken from among gay men, or heterosexual women, or drug users. But - from whichever population, it has to have an incident rate of about 2%-3% - the number of people getting newly infected each year. Otherwise it would take years and years and years to get an answer. Those populations [in which the rate is 2%-3%] are relatively uncommon: middle of Africa; Asia (i.e. China and India); prostitutes in Bangkok; gay men in urban settings.
The problem as I perceive it is that the major funding agencies - which, in this area, essentially means governments, national institutes of health in the US, France, the UK, Australia and Canada, Gates and other foundations - believe that it is important to conduct these studies in the developing world.
I am diametrically opposed to that. There is no a priori requirement for a study to be done in a developing country in order to be of benefit to the population of that country. There is no evidence of a difference in response to drugs between somebody in a village in Uganda and somebody in the center of London.
Furthermore, since 2001, there have been at least four aborted studies - one among African women, which was completed but didn't give answers; one on prostitutes in Cambodia, which was an absolute disaster, because of political issues; and a couple of others that got nowhere. A good $60 million has been essentially wasted on this.
A group of us have felt that the [pre-exposure prophylaxis] study should be done among urbanized gay men, and in parallel, or afterward, much larger studies could be done among heterosexuals in appropriate settings to provide the answer of whether [the results] are transferable [elsewhere].
What you're saying, then, is that if you were able to prove something by studying a group of gay men in, say, San Francisco, you would achieve the kind of results that could be extrapolated for Africa?
I'm saying that if [the funders] want to protect African women, it is probably better to conduct the study in gay men in London, Sydney and Amsterdam.
Perhaps gay men are partially responsible for this situation, claiming on the one hand that HIV is not a homosexual disease, while complaining of discrimination where medical research is concerned, precisely because it is a gay men's disease.
I'll answer that by saying that I think some of the funders are mistaking my point. I am not a misogynist. This not an issue of gay men vs. women. It is an issue of getting the answer in the most efficient way. The reason I believe it is more important to focus the study on gay men in a particular setting is not related to the fact that they're gay or that they're men, but to the fact that they are getting infected at a particular rate. The Health Protection Agency has just published independent data showing a 3% HIV incidence rate in gay men in London. This is higher than almost any other reported group in the world.
Last year, $400 million-$500 million was spent on HIV vaccine development. The cost of doing a study of the kind I am suggesting is $25 million-$30 million. It's peanuts!
Not that vaccine development isn't important; we need a vaccine. But at 46, I will die before there's a vaccine for HIV. All vaccinologists agree. But, of course, they can't say that.
I told Gates: "You can easily afford to pay for the study of gay men and a study on African women, and you'd still have change left over from what you'd spend on useless research that's not going to work."
What about intravenous drug users? Isn't sharing needles part of their "high," the way having multiple sex partners is part of yours, as a gay man. How can you counteract behavioral patterns through disease research?
There was almost no culture of sharing needles in the UK, where they are freely available; you just go and buy them in a pharmacy. But, of course, in New York or in Italy, you couldn't, so there was a need for sharing. But then - as often happens with cultural phenomena born of necessity - it became a kind of fetish.
The invention of the birth control pill led to what has been coined the "sexual revolution." If a prophylactic for AIDS is created, won't this have consequences as well?
I've used the example of the birth control pill as a reason for pre-exposure prophylaxis research. First of all, it emancipated women, and PREP could produce a degree of emancipation - because it is a form of protection which gives you choice. This doesn't necessarily mean that the choice enables you to have a better life. Secondly, one of the arguments against PREP is that you're giving people who aren't infected very dangerous HIV medication. Well, actually, contraceptives aren't very safe either.
Then there's Viagra - the most fantastic example of where the market has taken the lead. Viagra is no longer a drug; it's a commodity, though it has side effects and occasionally kills people. But we have made a value judgement that having and taking Viagra is better than not having it. When people are denied the choice of an addition or alternative to condoms purely because of a paternalistic view of the society that regulates access to that alternative, it is more an issue of politics than health. I actually think that the private industry often accused of only wanting to make a profit is more liberal than the public institutions that are supposed to fund suitable academic research.
Doesn't that have more to do with the marketplace than with medicine?
Yes, but I think it's also about viewpoint. It may even be due to the kindness of the people who work in those industries.
Are there no moral aspects to the issue of HIV prophylaxis? One could argue that if the birth control pill hadn't been invented, there would have been far less promiscuity, and that today there might not have been an AIDS epidemic to begin with. In other words, aren't pills that provide "choice" enablers of slipping societal behavior?
Read your history books! From mid- to late-17th century, Christmas was banned in the UK by the Puritans. It was actually a serious offense. Everything in life is a pendulum.