Much has been going on in the world of HIV, sex and drugs in the last month or so; the US marines recruiting at gay community centers, more mysteriously disappointing study outcomes for PrEP, encouraging news about the effect of microbicide gels against herpes, a new super-easy condom with a brand name that will put off anyone who cares about staying power.

I’ve ignored it all. That’s in part because I’ve discovered a site that really says everything that needs to be said about HIV prevention. Particularly insightful, in this post entitled “usefulness connected realizing hiv indicators”, is this gem:

“For that faculty your body gets very suasible to numerous germ infections and so the indicators are sure not e’er the HIV symptoms. The true unique method to aver that a soul is with HIV is the HIV checking.”

I don’t think I can add to that. Which is my polite way of saying that I’m taking a sabbatical from HIV and epidemiology. I plan to spend the next year or so travelling around Indonesia, eventually writing a book about this wonderful and mad land. Which has it’s own fair share of Bad English, as you can see over at my new blog, Portrait Indonesia.

I’ll be spending a lot of time out of range of wi-fi etc., but will try and post at least weekly. If you’d like to follow my progress, you can sign up here.

For now, on the subject of sex and drugs, it’s over and out. Thanks for taking an interest over the last four years.

It’s not that often that I sit reading the FT on a Tube full of morning communters. Even less often that the Pink Paper (no, boys, not THAT Pink Paper) carries full page ads from the Purveyors of Porn. The ad is pimping a new internet domain ending: .xxx (Slogan: Coming, now!)

The porn industry is positioning itself anew (they don’t excuse the pun, so I wont either) as responsible citizens, protectors of children and the integrity of your credit card details. Re-registering your porn domain with a .xxx extension will make it easier to filter, keeping it away from kids and the easily-offended. Since all .xxx domains will be screened daily by Mcafee, they will be virus-free. The xxx admin folks will also enforce standards of financial transaction probity, apparently. In the meantime, they stand to make an awful lot of money themselves. But here’s my question: what does it say that the ad was placed, as a FULL PAGE, in the world’s most prominent financial organ? Perhaps that purveyors of porn have more to invest than the rest of us?

Certainly, the porn industry could do with brushing up its image after the recent kerfuffle over HIV transmission on porn film sets. Though plenty of people are demanding the introduction or enforcement of condom-only porn shoot rules, I suspect they are on a hiding to nowhere. Isn’t the whole point of porn that is is a bit transgressive? If condoms were sexy, we probably wouldn’t have reached over 60 million HIV infections to date. Goody-two shoes safe sex is rarely enough the stuff of our reality; it is almost never the stuff of our fantasies.

The Salon piece acknowledges this. It fails to stress another important point. Most of the on-set transmission of HIV occurs right after the infected person themselves became infected. This is a time when there is tonnes of virus floating around the body and it is very easily transmitted. It is also a time when antibodies have not yet developed. Since the standard HIV tests are for antibodies rather than the virus itself, they will miss these very new, very dangerous infections. Indeed it was a classic case report from the porn industry that confirmed in life what we suspected from lab work about the dangers of early viral load.

Possible solutions: set a minimum time between shoots of six weeks. That way, if someone gets infected on one shoot, they’ll test positive before the next one. Another solution would be to invest some of the massive profits of the porn industry in testing actors for the HIV virus itself, rather than for antibodies. Both of these solutions seem unlikely, given the profit imperative of porn, but in my mind they are both less improbable than condom-only porn.

One thing that interested me about the .xxx ad was that they are offering, for a small, one-time fee, to BLOCK names from being used with an .xxx extension. Do you think I should sign The Wisdom of Whores up to prevent our good name from being abused?

Apologies if this post looks odd. My first attempt to post from an iPad.

It’s no surprise to anyone that I’m interested in viruses. Many know of my on-going affair with Indonesia. Some will have heard me obsess recently about using art to make people think differently about science. And a handful will know of my growing interest in digital media.

Conveniently, Icelandic singer Björk has brought all those interests together into a single tidy package. Her new Biophilia album is a great big muscial sciencefest. One of the first “single” apps released is called “Virus”. Just when you thought there was no new angle on soppy songs about codependent love, she’s written a song about, well, a virus, and its interaction with host cells. Among the lyrics:

“The perfect match, you and me
I adapt, contagious
You open up, say welcome”

It’s played on a sort of mish-mash adaptation of a gamelan, Indonesia’s favourite instrument. And its being released as an app which people are invited to remix, play with, adapt, take forward. Which doubtless has many in the music industry wondering: if this mutate into something truly virulent, how soon will it kill its host?

Taking anti-HIV pills every day cuts the risk of infection by 63%, said CDC researchers in Botswana. It cuts infection by up to 73%, said University of Washington researchers working in Kenya and Uganda. That’s great news, of course.

Here’s why I’m confused. The larger of these trials was conducted in 4,758 “discordant couples”. [I earlier incorrectly reported that both trials were in discordant couples. The CDC trial in fact recruited 1,200 sexually active uninfected heterosexuals, regardless of their partner status. Full inclusion and exclusion criteria here]. That means researchers in the large discordant couple trial knew that one person was infected and the other uninfected. They chose to give drugs to the uninfected person, to see if it would stop them becoming infected. And it does, in over 60% of cases. But another recent study shows that if we give the drugs to the infected partner, the one who might actually need these same drugs because they have HIV and need it surpressed, it cuts infection by 96%. So in the case of discordant couples, it seems to make much more sense to give the antiretrovirals in question to the infected partner.

That leaves us with the question: who should get PReP? Right now, there are not enough antiretrovirals to go around to treat all the sick people who need treatment. If we’re going to use them selectively for prevention, we should start with the most effective use, which appears to be early treatment of the infected partner in discordant couples. We could also give them to people who aren’t in a couple but who know that they’re likely to get around a bit and might want to stay safe without using condoms. That’s potentially a lot of people; it will stretch our purses. But more than that, it will stretch our political will. Let’s face it, HIV has reached eye-watering levels in many sub-Saharan African countries because both voters and governments have been in deep denial about their own, and their neighbours’, propensity to have sex with someone who is not their single life-time partner. Some people, including influential religious and community leaders, even continue to believe that giving out condoms encourages licentious sex. To them, giving out ARVs will surely mean encouraging licentious unprotected sex (if you’re anti-condom, is that better or worse?).

So who is PReP for? We’ve got a better option for discordant couples. We’re not going to want to give it to randy adolescents. We know it works for gay men, but some of the countries where the trials took place would rather thump or jail gay men than protect their sexual health. We’ve no idea yet if it works for drug users (though a deeply unethical trial by CDC in Thailand will tell us that soon.

Of course PReP will find its niche; when people actually take it it works really well (though not as well as abstinence, when people actually abstain, or condoms, when people actually use condoms). We’ll find out a bit more about just how well at the annual AIDS circus in Rome next week. I’ll look forward to learning what the actual incidence rates in the studies were, and more about sex differentials and adherence. But I think we would be unwise to rush around talking about massive roll-out of PReP before we actually figure out who it works for in the real world.

As an aside, the results have a huge potential impact for Gilead, manufacturer of both Viread (bascially tenofovir, one of the pills that worked in the trial) and Truvada (the tenofovir – emtricitabine combination that was the other). Gilead has come over all generous and has started letting Indian and other developing country companies copy their products. They’ll take a 5% fee; if we really do go for a massive roll-out of PrEP, that will keep drug costs down globally, while giving Gilead extra cash for very little effort. A win-win situation for which they should be congratulated.

A second aside: The CDC trial is confusing in a different way. In December 2009, CDC announced it was terminating the trial of Tenofovir for HIV prevention because they’d had so many drop-outs that the trial would be unlikely to show results even if they doubled the size of it. They kept it going not as an efficacy trial (testing Tenofovir against a placebo) but as a safety and behavioural trial (clocking how good people were at taking their pills, looking for side effects etc.). So it was quite surprising to find them leaping forward with efficacy reults, of which more details here.

Thanks to Eva for pointing out my error.

Do we really need research to demonstrate the blindingly obvious? Yes, if you believe that people who call the political shots will change their mind on the basis of a published study (something about which I am skeptical) So here we have it: research published in the International Journal of Impotence Research shows that guys over 40 are less likely to have droopy dicks if they are fit. I’d say that’s no surprise to the many millions who use the work “fit” as polite bar-room slang for “fuckable”.

As a result of this groundbreaking research, we can put numbers on things that even the smallest amount of participatory research might have taught us: guys who are flabby are over four times more likely to droop than those who are fit. What’s interesting to me about this research is the conclusion: “This study reinforces the concept that healthy habits have a direct effect on erectile function.” No mention, at least in the abstract, of the organ that affects sexual performance more than any other: the brain. If you’re flabby you’re more likely to feel generally droopy about yourself, less likely to be in a position where your erectile function even gets put to the test, and more likely to be anxious about it when you do get the chance to perform.

Here’s another research question: what’s the likelihood that research such as this will have people trading in their blue pills for gym passes? Or that the public health industry will ever change its incentive structure so that people stop getting rewarded for publishing “so what?” papers?

That’s huge. So huge that the study was stopped early. We still don’t have many details about things that I would find interesting — how good were people at taking their pills, did they people on meds have more or less unprotected sex than people who weren’t on pills, etc. — but it seems incontrovertible that if you’re infected with HIV, one way to protect your sex partners is to start taking antiretrovirals when you’re immune system is still in relatively good shape.

I’m still left with two major questions. First: it is clear you’ll protect your partners, but will you protect yourself? What do we really know about the long-term effects of taking antiretorvirals early for your partners’ benefit? We’ll get more information about that from another trial by the same group, but they’re not scheduled to report for another five years. People who got treated earlier in the the treatment-as-prevention trial were just as likely to die during the course of the study as those who didn’t, though encouragingly, they were signigicantly less likely to get sick with TB. It may well be that starting meds earlier is good for the infected person as well as for those they shag.

Second major question: this study (known as HPTN 052) has made it clear that an HIV infected person whose CD4 count is between 350 and 550 when they start treatment is less infectious than a person who doesn’t start until their cell count falls below 250. For those individuals, treatment is prevention. But does that necessarily mean that expanding treatment will reduce new infections at a population level? For an interim period, at least, it may well not. Before I’m accused of raining on the parade yet again, I want to point out that the same question was raised by Myron Cohen, the principle investigator of HPTN 052 in an e-mail exactly a year ago. Speaking of a stampede towards using earlier treatment as a means of prevention, in part as a result of a lot of “utopian” modelling, Myron said:

“I am not convinced that this will all come out the way it now appears, and we do not yet know how to measure population level benefit of ART, if it is to occur.”

Logically, if you reduce the infectiousness of every infected person by 96%, new infections will fall very dramatically. But we know that can’t happen. It certainly can’t happen overnight. It’s worth noting that genetic analysis of the virus shows at least 18% of the new infections in the study (and possibly up to 28% — not all the analysis is finished) came from someone who was not the “regular partner” recruited into the study. Until everyone gets treated sooner, those infections will continue. Indeed some will continue even with universal earlier treatment, because some will probably have come from people who are newly-infected, very infectious and unlikely to be treated. That’s a continuing worry in places where the all-too-visible face of AIDS-related emaciation, disfigurement and death prompted a change in behaviour; less sex, fewer partners, more condoms. As expanded treatment removes that visible death-mask, communities revert towards pre-AIDS behaviours. Where condom use rose rapidly, for example among gay men in rich countries, it has fallen back since relatively early HIV treatment has been universally available. The effect may be less pronounced in the hyperendemic countries where behaviour has not changed all that much, but it’s something to watch out for. More unprotected sex with a variety of partners also pushes up STIs, and an active STI can in turn unleash spikes of HIV in the genital fluids and undermine the protective effect of antiretrovirals. Note that I’m not talking here about the behaviours of discordant couples who have been to counselling and are on HIV treatment, I’m talking about people who believe (or assume, or just hope) that both they and their partners are negative.

It’s perhaps worth clocking that researchers shifted their original “deferred treatment” threshold to a CD4 count of 250 (from 200) when the WHO treatment guidelines (and the national guidelines of many countries they were working in) shifted. They did not, however, change it again when WHO guidelines were revised upwards again to 350, because “the second revision was not readily adopted by all of the countries participating in the study, primarily due to a lack of drug supply.”

The fact that 1.8 million people died of AIDS in 2010 confirms that many countries have trouble getting drugs even to those people who depend on them for survival. Getting them to the larger number who might benefit from them as a transmission risk and TB reduction measure will be harder still. That will eat into the potential prevention gains in two ways — obviously people who don’t have drugs don’t have lower viral loads. But relatively healthy people who sometimes have drugs may present more of a transmission risk than those who never do, because HIV tends to spike upwards into a brief, highly infectious phase when treatment is interrupted. Frequent interruptions can undermine the effectiveness of the drugs; resistance is another source of nasty, infectious spikes in viral load. Though we don’t yet have any information about adherence, we can assume that people in the HPTN 052 trial had uninterrupted access to meds, and we know from the study protocols that they were actively encouraged to keep taking them. We also know that they deliberately excluded drunks, people with drug problems, people with mental problems or “Any condition that, in the opinion of the study staff, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives”. In the real world, we can expect a more erratic drug supply, sloppier adherance and bouncier viral loads. That may will turn in to protection of far less than 96%.

Overall, more people on treatment means, we hope, more people living longer, healthier, more sexually active lives. That also means more opportunities for sex with someone when viral load is spiky, and thus for onward transmission over HIV. Add together more unprotected sex with people who may be in not-yet-treated primary infection, and more sex during times after the start of treatment when HIV is bouncing around because of STIs, treatment interruption, treatment failure or whatever. If the sum of those two adds up to more than the sex a person has between the time their CD4 count hits 550 and the time it would otherwise have hit 250, new infections are likely to rise, even if earlier treatment reduces transmission during that notional window to zero.

That is absolutely no reason at all not to push to use antiretrovirals to reduce infectiousness in people who are infected. I am persuaded that we should be doing that, and I think HPTN 052, with its relatively sober threshold for starting even the “early” treatment points us in the right direction. But I think it will be a long time before we have the cash and the systems in place to make this an effective prevention tool at the population level. And since none of the other prevention tools we have are working very well at the population level either (at least in unpaid sex of any persuasion), we certainly can’t declare victory quite yet.

It’s a huge disappointment to those who were hoping that the pill-a-day-to-avoid-a-pill-a-day solution might drag us out of the despond that we’ve been in as we contemplate 2.7 million new HIV infections this year. That’s the same number as were newly infected when I started in this business 15 years ago. The only real change is in the cost of our failure: that’s increase over 70-fold.

The study, well conducted by my former employers Family Health International in four countries, is at odds with a study released last November, that showed that a daily dose of Truvada, a combination of two antiretorvirals in pill form, cut the risk of infection among gay men by over 40%. The earlier study did show that — surprise surprise — taking pills to prevent HIV doesn’t work unless you actually take your pills. Though virtually everyone said they took their pills, a later analysis of blood samples showed that wasn’t true. We don’t yet have that same analysis for the new trial in women (dubbed FemPrep), so although 95% reported taking their pills, it’s possible that real adherence was much lower. More than possible: likely. All women in the study were taking contraception, but there was a 9% pregnancy rate, apparently much higher in women on the pill than women on injectibles (we don’t yet have the actual numbers). That suggests that some women aren’t all that good at taking one pill a day (I’m one of them; thank God for implants), let alone two.

There’s a real possibility that antiretrovirals taken through the mouth and processed through the digestive tract aren’t as effective at preventing HIV from finding an entry point in the vagina as they are in the rectum, hence the difference between the trials in straight women and gay men. If that’s the case, it ups the ante for putting ARVs directly into your fanny (using fanny in the English sense!). We know from the Caprissa trials that antiretroviral microbicide works vaginally (though not necessarily rectally). But we only know that it works if you “shoot up” both before and after sex; in theory, at least, that is what was being tried. In practice, we know (well, strongly suspect) how unlikely it is that women will actually do that on a long-term basis. We now desperately need trials of a one-shot vaginal microbicide. Because for all the talk of “bio-medical solutions” the confusing results of recent HIV prevention trials remind us that most bio-medical solutions have a very strong behavioural component. Pills that “work” if you take them are no good if they make you feel so sick, so choked, or so fed up that you don’t take them.

One of the things that pleased me greatly about the FemPrep trials was that researchers made sure that the women who volunteered for the research knew about the disappointing results before the press or the scientific community did. There are more details from the study teams about how they interacted with participants on this interesting conference call, arranged by the ever-helpful AVAC network.

This post must end the way these posts seem always to end, with an underlining of the shockingly high rate of new infections in the study overall: five percent of women became infected, despite the fact that they were given female and male condoms, were regularly screened for other sexually transmitted infections and treated as necessary, and counseled up the wazoo. It’s a reminder of how badly suited the tools in our current toolbox are to the job of HIV prevention, and a caution about expecting much more from other behavioural interventions such as the use of pills or gels.

The screen shot above shows a small corner of Filth Fair, a new, quite clever word game app commissioned by the somewhat staid scientists at The Wellcome Trust to go with their new Dirt season. On the left, the app before the Apple censors rejected it. On the right, the revised version. Even then, it has a 17 age rating; though the censors don’t have to give reasons for their decisions it appears that they remain upset about the use, hidden within the painting/puzzle of the words sex and pornography.

I remind you that these censors sit in a country which allows pregnant girls to marry at 14 in some states. To see a fig leaf on your phone, though, you have to be 17.

The Apple censors didn’t apparently, think there should be any age restrictions on homophobia. A recent app from Exodus International that seeks to cure people from the affliction of being gay was released with no age restrictions. Needless to say, there was quite a bit of protest. I’m glad to say that sense beat the censors, and the anti-gay app has been removed.

If you’re in London, I’d urge you to visit the Dirt exhibition. Perhaps because of my own dirty mind, I got roped in to writing a chapter for the book of Dirt, that goes with the exhibition. There’s quite a lot of fun stuff in it, quite apart from the sex and drugs bits.

Mr. Gates says we can eradicate polio in two years; that just a fifth of the time that it took his Internet Explorer to eradicate Netscape.

Gates has certainly put his (foundation’s) money where his mouth is, some 300 million dollars over the next couple of years. And he has some very good brains working on crushing the bug. But my own feeling is that the virus will be rather harder to wipe out than the browser that we all loved so well.

As I imply in an essay in this month’s Prospect, I suspect the only way we’ll achieve Mr. Gate’s goal is by defining “eradication” as wiping out wild-type polio. But that leaves us with the quandry of what to do about the weakened-but-still-live virus in the oral vaccine, the only vaccine we can afford to use in the countries where polio still circulates. Once re-established among kids who weren’t properly immunised despite dose after dose of vaccine (usually because they shit it straight out with their chronic diarrhea), it can revert to become as virulent as it ever was in the wild.

To get rid of that we need to switch to expensive, cumbersome injectible vaccines, or develop a killed vaccine that is cheap and easy to deliver. It’s not clear that it’s worth spending money on either. As richer countries re-evaluate their development spending (as the UK did today — nicely summarised by IDS’s Lawrence Haddad) we need to focus on what delivers greatest bang for buck. Hunting down the polio virus that hangs out in guts, drains and labs and crushing it makes jobs for epidemiologists, but it sucks time and money from other things that kill, maim and ruin the lives of far more than the 1,000 or so people who now get polio each year. Improving drains, making roads safer and diagnosing treatable infections earlier aren’t as sexy as wiping out polio, but we should allow ourselves to be seduced by them more often.

The broadside against the culture of data-hoarding that dominates in public health is published today in a joint statement on data sharing signed by 17 institutions, including the three biggest funders of public health research globally: The U.S. National Institutes of Health, the Bill and Melinda Gates Foundation and the Wellcome Trust. Other signatories include the World Bank, the U.S. Centers for Disease Control, national research councils from the UK, France, Germany, Canada, Australia and New Zealand. (Here’s the full list.)

I’d like to have had a more bombastic introduction. “From this day forth, all data collected by researchers who are paid by taxpayers or tax-exempt charities will share those data with the world”. I implied as much in a comment in the Guardian. Actually, the statement doesn’t go anything like that far. Indeed it’s pretty fluffy, couched in terms of principles and goals rather than requirements. But having helped draft the fluff, and been part of nearly three years worth of discussions leading up to it, I think it is a damned good start. Perhaps surprisingly, many of the key institutional players would have liked to go much further, but they were shouted down by their legal departments.

So the statement doesn’t actually commit institutions to do anything concrete. But implicit in its goals are important changes to the culture that makes us researchers so mean with our data. These mega-funders say they aim to reward us for publishing data, not just papers. They aim to support data management, so that data can be shared practically. Data management has always been the most neglected and undervalued part of the research enterprise in public health (something I’ve ranted about before in print (pdf) and on air; I’m looking forward to researchers rewriting their budgets so that the funders can put their money where their joint statement is. And they aim to make sure that the scientists in developing countries who do a lot of the grunt work of collecting data of interest to global health do not get “scooped” by data munchkins sitting in Seattle or Geneva with squigabytes of processing power and a constant electricity supply. The equity principle was firmly stressed in a commentary about data sharing published in The Lancet today to go with the Joint Statement.

Some researchers will feel queasy about sharing their data; it is hard not to feel ownership when, night after night after exhausting night, you’ve driven your motorbike at 4.30 am through the entrails of the red light district in the rainy season to get them to the lab in good order. But the truth is that “my” samples, and the data they produce, are first and foremost owned by the people who gave them to me — and data tied up on my hard drive waiting for me to get around to writing that third paper about the study (when I’ve finished my next grant application and the IRB paperwork for my current study) are not doing those people any good at all. The other thing that we’re all worried about is that other people will get to see how filthy our data really are. But that’s surely a reason to let more light in, not less.

So today’s statement, fluffy though it is, is a cause for major celebration. The funders say they are putting together working groups to start developing the infrastructures and data standards we need, as well as to change incentive structures so that universities as well as funders support data sharing. It’s up to us researchers to muscle in to those working groups, to make sure that an Open Data world works for us as well as for our paymasters and, most importantly, the people who we prod, poke and bleed in our studies.