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.

Tom Scott has produced a series of handy-dandy stickers to put on newspaper articles. Here are a couple of my favourites, but you can see the whole set here, and even print out your own set.

What I’d like Tom to get on to next is a set of stickers to help me quickly find the crap research in peer reviewed journals. He could start with “Warning: This paper was reviewed by someone who has applied for a job with the first author” and “Warning: Reprints of this article ordered by Big Pharma will account for 18 percent of the journal’s income this month”.

Thanks to CB for bringing Tom to my attention.

I’m hoping that’s true of today’s front-pager on data sharing in health research. The story hypes the idea of data sharing as a brand new one. In truth, public and philanthropic funders of health research have been working for a while to develop a common approach to promote data sharing. They’re due to publish a “Joint Statement of Purpose” on efforts to promote data sharing very soon; if they back the rhetoric up with the people and money needed to do some of the tedious work that will make shared data sets valuable and easy to use, the New York Times story could look very dated, very soon. But it’s a big if. Many scientists are still very resistant to sharing, for reasons that are quite nicely described in this article in the Chronicle of Higher Education. At least one of the major philanthropic funders of health research keeps asking for proof that more minds working on large, combined data sets will yield results faster than if everyone sits in their own labs, each collecting fragments of similar data and analysing it separately. That’s like software companies questioning whether open source code development is more efficient than proprietary code development. Oh, wait a minute…

The really interesting thing about the Alzheimer’s example described in the Times is that private companies are in the mix, too. Ultimately, academics funded by taxpayers and charities will share their data because their paymasters tell them to. If those same paymasters also do something to remove the disincentives to share data that come from using publication in peer reviewed journals as the only yardstick of success for scientists, it will happen even faster. But the GSKs and Pfizers of this world don’t think peer reviewed papers are the be all and end all, and they are certainly not signing on to any Joint Statement of Purpose on data sharing. (Our invitation to them to be part of the discussions were met with a resounding silence.) If Big Pharma has decided that data sharing is the way to go, then it’s more than a new trend, it’s the new orthodoxy.

The first step backwards is of course that counterfeit drugs usually don’t work very well. But people who take them presume, at least until they get hopelessly sick, that they are working. They believe their viral loads are falling, and they believe that they are getting less infectious. We already know that people get sloppier about using condoms it they think they are not infectious (or, if they are uninfected, that any HIV-infected partners will be on meds and not infectious). So it’s not encouraging to think that those may be the very people whose viral load is bouncing skywards because they are on ineffective medication. Oh, and that resistance is almost inevitably going to rise because people will be on and off “real” medication depending on the supply.

The second step backwards is that this kind of thing gives the self-appointed guardians of Big Pharma’s bottom line a new cudgel with which to bash generics and compulsory licensing. And sure enough, there they are today, wielding the cudgel on the op-ed pages of The New York Times. (Note the source of Roger Bate’s funding…) Conflating generics with counterfeit drugs is like conflating sex work with trafficking. One provides services people want at a price they agree to pay, the other is illegal and dangerous. But waging war on the first is almost certainly going to make it harder to wipe out the second.

A CD4 Molecule

A new study suggests that people with HIV have a 70% greater chance of staying alive if they start taking antiretrovirals when their CD4 count is as high as 500. That’s good news for people who know they are infected early on and who have easy access to drugs. It’s also potentially good news for the people who make the drugs, bumping up their market size quite substantially.

CD4 molecules are attached to T-cells that defend the body against infection. CD4-bearing T-cells get knocked out by HIV infection; so the number per microlitre of blood is used to track the progress of HIV as it cuts its destructive swathe through the body. The US currently recommends starting antiretroviral treatment when the CD4 count hits a low of 350. The new study, which pools data from a large number of north American patients, suggests that a significant number of people die before they hit 350. The study’s author Mari Kitahata was involved in developing the existing guidelines, but in view of the new data she suggests people should start taking drugs when their CD4 count hits 500. Kitahata, a highly respected researcher at the University of Washington who provides advice to several pharmaceutical firms, is now investigating whether there’s anything to be gained from taking drugs even earlier in the course of infection.

This news will cause consternation in a lot of developing countries, where current guidelines recommend starting people on meds at a CD4 of 200 — a level which more or less goes hand in hand with symptomatic AIDS. Raising the threshold to 350 would mean hundreds of thousands more people would need to be put on meds. A threshold of 500 would mean millions more people needing uninterrupted access to expensive drugs. This would cost a fortune; at the risk of sounding callous, I think we would be very well advised to make careful estimates of exactly how many additional lives would be saved. Obviously, doctors treating people with HIV want to keep their patients alive. To them, and of course to the patients, a 70% decrease in the chance of dying is pretty persuasive. But in real terms, not all that many people are dying in the US cohorts (3 per 100 person years among those who took drugs earlier, against 3.2 per 100 person years among those who took drugs later). Kitahata and her colleague Daniel Kuritzkes were abit vague about the costs and benefits of getting people started on drugs earlier; check out the transcript of a press conference discussing the study results over at The Body. (The transcript also contains newer data than the published abstract.)

One thing that wasn’t discussed at the presser was the potential downside of being on antiretrovirals for longer than is necessary. I’d be curious to know more about the long-term effects of taking antiretrovirals, how many extra years of drug-taking a higher threshold would imply, and whether, at a population level, the extra years of drug-taking would mean a lot more discomfort and sickness related more to the drugs than the virus. It’s a very difficult thing to look at, not least because drug regimes have improved so much over time. But I’d welcome information from anyone who has looked at these issues.

If we are going to try to provide drugs earlier, it’s one more reason to push for more routine HIV testing among the people most likely to have been exposed to the virus. Even in the highest risk groups — in the US and the UK that would be gay men — between a fifth and a quarter never learn of their HIV infection until an AIDS-related condition lands them in hospital or at the doctor’s clinic. That’s usually way after the CD4 count has crashed through 500 and even 350. Earlier treatment depends on earlier diagnosis. In countries which might just put people on treatment earlier, these data might just persuade more people to find out if they’re infected.

HIV medicine advertising: In the toilet

As competition to treat people for HIV has hotted up, pharmaceutical companies have started dumping on one another. Using innuendo and not-quite-stated factoids, they are beginning to imply that the rival camp has something to hide (something they’ve no doubt learned from political campaigns). Those other drugs are toxic, discolouring, inconvenient. Activist groups and HIV bloggers such as Peropheries are upset, but I wonder if Big Pharma might actually be doing us a favour.

I first saw the loo ad above looming down at me in a huge, back-lit poster form while I was wandering around New York one evening recently. It’s from Bristol Myers Sqibb — they make Reyataz, an antiretorviral which apparently doesn’t send you to the loo every two seconds. Sadly not true of Kaletra, made by rival Abbot Laboratories. Though this ad doesn’t actually point the finger, it’s a pretty good start as smear campaigns go. This and other examples have been picked up in a story by The Wall Street Journal, relayed by the always helpful Kaiser Family Foundation.

Treatment activism groups are upset because they think negative advertising might discourage infected people from taking their meds at all. That seems to me unlikely — the runs is an unpleasant but relatively small price to pay for an AIDS-free life. I do think we have a right to be upset about what these cut-throat smear campaigns tell us about what the marketing gurus think is acceptable corporate behaviour in our hyper-capitalist world. But I also think that the relentlessly upbeat advertising that has been the norm for HIV meds for years now might be just as damaging. The message: “Don’t worry if you get HIV, you can still go rock-climbing with your friends at the weekends”, has surely contributed to the “so what?” attitude that has led to rising risk behaviour and HIV rates among young gay men in many places. Perhaps inadvertently, Big Pharma is now sending a different message: being on HIV meds for the rest of your life may not be such a painless thing after all. As I said, I don’t think these ads are going to discourage people who are already infected from taking their meds. But they might just help on the prevention front, by signaling to uninfected people that it’s perhaps worth making a bit of an effort to stay that way.

Activists have done a spectacular job in slapping down the price of antiretroviral drugs in the last five years. They’ve rallied big names like Bill Clinton and marshalled huge funders like the Global Fund. Even US-funded PEPFAR, once laughingly known as Purchasing Expensive Pharmaceuticals from American Retailers, is spending money on cheap generic drugs. All the while, Big Pharma has warned that eroding profit margins by pushing prices too low will discourage new investment in research.

Roche has been careful not to make a direct connection between low prices for HIV-related drugs and their decision to stop research in the area, even off the record. And there are good reasons for the decision — they were not a huge player in HIV in the first place; less that 5% o HIV related drug sales are from Roche. Many of their drugs are designed to help people only after other, more common treatments fail. And one of their most effective products is unpopular because it has to be injected rather than swallowed.

Is Roche’s announcement a shot across the bows of advocacy for cheaper drugs? “Stop eroding the profits we want, or we’ll stop inventing the drugs you need?” It’s hard to say, but I am amazed that the question is not ringing loudly around the blogosphere. I support the achievements of groups that have fought to bring down drug prices with every fibre of my body. And I certainly find it hard to feel sorry for an industry that spends far more on marketing than it does on research, and that consistently makes its shareholders richer. But is there a point when we have to start discussing how much is enough when we press commercial firms to lower prices?

One solution to the return-on-investment dilemma of is of course to provide more public funding for the development of drugs that meet the needs of poor people and poor countries. There’s been a fair bit of progress in finding public funding for vaccine research, so it’s especially depressing that yet another vaccine trial has been canceled because researchers think it’s unlikely to produce good news.

Do I believe we need to rethink our approach to AIDS? Absolutely — that’s why I’ve written The Wisdom of Whores. But what I’m promoting is a completely different type of rethinking, almost exactly the reverse of the denialist approach. We agree that a lot of people in Big Pharma and the Do-Good industries have made a lot of money by manipulating the facts about HIV. We also agree that we’ll never conquer AIDS unless we start confronting the facts. But we disagree profoundly on the facts (which are, for the record, that the HIV virus, which is transmitted through contact with the blood or genital fluids of an infected person usually during sex or drug injection, attacks and eventually destroys the human immune system).

The denialists believe that we’re not conquering AIDS because we’re treating it like an infectious disease. I contend that we’re not conquering AIDS because we’re NOT treating it like an infectious disease.

By all means read their screed and watch their videos. In my opinion, the denialists want to substitute a new form of denial (HIV-doesn’t-cause-AIDS) for the existing form of denial (sex-and-drugs-don’t-cause-AIDS). It’s hard enough getting public health officials to recognise that most people contract HIV when they are doing something they know is risky because they want to get high, get laid, or get paid. It doesn’t help to add another distortion. (Re)think about it.

A growing number of scientists are now turning down these invitations, or doing the gigs for free, according to a report by Gina Kolata in the New York Times. Several scientists are quoted in the story as saying they feel their reputation is compromised by taking these payments, even when there’s really no conflict of interest involved. And if that’s how they feel, I can understand them turning down the cash. On the other hand, it is important that the voice of independent scientists be heard in pharmaceutical industry discussions and on their governing boards. And since expertise is a commodity which individual scientists invest heavily in over a lifetime of research, it doesn’t seem so outrageous that they should get paid for it. That’s particularly true for people in the increasingly common position of being quasi-freelance, having to bring in most of your research money yourself. Time you’re spending talking to industry execs is time you’re not at the lab, or with patients, or crunching data. I’m all for avoiding conflicts of interest. But if we get so paranoid about being seen to “consort with the enemy” that we won’t even engage in discussion with industry, science will be the loser.

The HIV concession brings Indian Railways’ list of socially-motivated discounts to 50. Some of my favourites are ” Either of parents accompanying the Child Recipients of National Bravery Award – travelling for any purpose” (50% off) and “Persons taking part in Mountaineering Expeditions organised by IMF” (75% off). Since I’ve been exposed to all those Big Pharma ads in which good-looking muscle-bound guys pop their antiretrovirals before climbing a glacier and abseiling down it, I’m wondering: Do HIV-positive mountaineers get a double-discount?

Seriously, I think this is good news for three reasons. Firstly, it may actually make it easier for people to get their treatment. Secondly, it is an indication that the appalling miasma of stigma that hangs over HIV in India may be thinning. And thirdly, it is an example of a “multi-sectoral response” that is actually useful. The fashion for trying to make HIV everyone’s business is often counterproductive. In most of the world we really don’t need oil companies holding concerts on World AIDS Day, or HIV task forces in the Ministry of Fisheries. We do need people who need sterile needles, condoms and treatment for sexually transmitted infections to be able to get them, cheaply and easily. Ditto people who need antiretorvirals. If Indian Railways initiative helps achieve that, bravo.