The question was raised for me while I am here in Thailand by a comment on an earlier post. It pointed out that US taxpayers, through CDC, are funding a trial among drug injectors in Thailand that withholds the very thing we know will prevent most infections: sterile needles.

CDC, on its website, points out that withholding clean needles is “consistent with Thai government policy”. And yet the agency itself recognises that needle distribution programmes reduce HIV infections. The Helsinki declaration on medical research ethics says that if you’re trying out a new drug or procedure, you’ve got to try it against the best available alternative.
In the past, I’ve argued that it is reasonable for us to read that as “the best alternative feasibly available in the country where the study is being done”. There’s no point trying a drug designed for use in a developing country against a developed-country regimen which is likely to be better, but which couldn’t ever be offered in the study country because it requires too much money, technology or expertise to administer.

The “we’re using the Thai standard of care” argument is very convenient for CDC researchers. After all, they need quite a few people to get infected, so that they can see if significantly fewer people get infected if they’re using the trial drug, tenofivir.* CDC’s other tenofivir trial, among women in Botswana, has just been downgraded, because the research team has realised that it is not getting enough infections in either group for it to be able to measure a difference. That’s in part because of very high drop-out rates — already a red flag for a prevention method that obliges you to take a pill a day for as long as you’re at risk.

We know that an adequate supply of sterile needles, and the freedom to use them without fear of arrest, can cut HIV infections dramatically among injectors. If the CDC study in Thailand gave enough needles to injectors, they probably wouldn’t have enough infections to give them a trial result. And the tenofovir-based prevention method that’s being tried is a method that could be used by other groups too — gay men and sex workers and other heteros at high risk of exposure, for whom we don’t have such easy prevention options. So you can understand why researchers are reluctant to push the envelope on providing decent prevention to study participants. But in this case, the “local standard of care” argument really doesn’t wash. It would be perfectly feasible for Thailand to provide injectors with clean needles. The country has the technology, the money and the health systems to do that. The only block is a political one. It’s bad enough that Thai authorities live with this blind spot in their otherswise quite pragmatic HIV prevention programme. The US has been just as bad at home, although there’s now light at the end of the tunnel for safe injecting programmes in the US. All the more reason that US researchers (and taxpayers) should refuse to compound Thailand’s unethical policy with unethical research.

*Info on the trials: The Thai and Botswana trials aim to investigate whether uninfected people can take a daily dose of antiretroviral drugs to stop themselves getting infected with HIV if they are exposed to the virus through sex or needle-sharing with infected people. It’s know as Pre Exposure Prophylaxis or PrEP, and you can find our a lot more about it here.

A month ago, the media got very excited about an HIV vaccine. Study results, released in Thailand with a maximum of fuss and a minimum of detail, showed that the two-step vaccine might protect about a third of the people who get the shots against HIV. Then the doom-mongers weighed in: without more information, we might be overestimating the effects of the jabs. So, is the syringe half full or half empty?

Now more details have been released, we’re still looking at half a glass. Hurrah! said some reports. The vaccine really is protective. Boo hoo, said others. Unless you torture the statistics, they don’t confess to much of an impact. I finally got around to combing through the full report of the trial in the New England Journal of Medicine. Both the optimists and the pessimists are right. It really depends on what your hopes and expectations were. If you are a basic scientist (as most of the people involved in the study were) you’d be pretty thrilled by the results, because they show that vaccines might one day work. If you are a public health boffin such as myself, you’d be pretty disappointed, because the study suggests that that this vaccine doesn’t work for the people who really need it — a point much underplayed in the official reports.

In their full paper the research team reported three sets of results for this study among young men and women in Northern Thailand; only the most optimistic of these was reported to the press in the initial release of results a month ago. Keith Alcorn of Aidsmap has produced a typically sound and balanced summary of the paper if you want more details. But here’s my more opinionated take.

Analysis 1: Real World.
This is technically known as an “intention to treat analysis”. The final analysis includes everyone who was enrolled in the study, regardless of whether or not they followed all the procedures correctly. This is the analysis which is most interesting to public health boffins, because it comes closest to showing how things might happen in the messy reality of life, where people forget to show up for appointments, get given the wrong dose by mistake, etc. In this analysis, people in the vaccinated group were 26.4% less likely than those in the unvaccinated group to get infected with HIV. There was a 92% probability that this difference was not due simply to chance; that means that the difference would not be considered “significant” by those who cleave to the mystical figure of 95% to dictate what is or is not worth considering. Taking into account random differences between the people assigned to the vaccine and the placebo groups, the researchers were 95% sure that the real effect of the vaccine did something between making you 48 percent less likely to contract HIV, and making you four percent more likely to get infected.

Analysis 2: Ideal World.
Known as the “per protocol analysis”, this looks only at the people who got all their shots on time, in the right doses. This is more or less the human equivalent of doing things in lab conditions, and is the sort of analysis that is most useful for basic scientists. Only three quarters of all the study subjects qualified. That in itself is worrying to people like me; if we can’t deliver four doses of vaccine to a quarter of the participants in an incredibly well-organised, well-funded study with hugely well-motivated study staff, how the hell are we going to do it in the real world? More worrying to the basic scientists, I would have thought, is the fact that in this sub-population of people who did everything exactly comme il faut, the vaccine did not have a more pronounced effect (26.2%, with an 16% chance that the effect was due to chance). Because numbers were smaller there was an even wider range that might have reflected the “true” outcome, from increasing infections by 13.3 percent to cutting them by 51.9 percent.

Analysis 3: Tidied-up World
Not a common convention, the “modified intention to treat analysis” essentially reflected the real world with the messiest bits knocked off. In this analysis, the researchers included everyone in the study, except the seven people who it turned out were already infected before their first jab. These people were missed in the initial screening test because they were still in the “window period” during which a person has the virus, but not yet the antibodies which cause a test to show up positive. They were discovered because they had turned positive by their last jab; the team then went back and used a (much more expensive) test for the virus itself on the original screening sample and found that they had already been infected. From a basic science point of view, it makes perfect sense to excluse these people from the analysis; obviously, a vaccine can’t protect people who are already infected. From a public health point of view, it’s debatable whether we should tidy up the data like this. If we put huge national vaccine programmes in place, we’re going to be vaccinating people who are in the window period, especially in the early years, and in groups at highest risk. I’d say we want to take that into account when estimating the potential effect of a vaccine. it was this “tidy” analysis that hit the headlines a month ago, and gave the study its only “significant” result — a 31.2% reduction in HIV infection, with a 96% probability that the effect was not a statistical fluke. This time, we could be 95% sure that the vaccine didn’t make things worse, that it reduced infection by at least 1.1%, and perhaps by as much as 51.2%.

As a public health nerd, I’m most interested in the Real World Analysis. But I’m even more interested in something that’s buried down at the bottom of Table 2.

Click to enlarge

Here, the research team looks at the effect of the vaccine on people with different levels of risk behaviour. In a shockingly poor piece of paper writing/ editing, it is not actually possible to tell from the Methods section of this paper how the different levels of risk are defined. But the definition for high risk does seem to include at least some of the usual suspects: needle sharing during drug injection, same sex partners for men, commercial sex etc. And what Table 2 shows is that the vaccine makes no difference at all for those at highest risk. It might cut infection rates by nearly half in that group, or it might increase the chance of getting HIV by nearly three quarters. The best-guess estimate is that it cuts infection rates by under 4% among the people who are most likely to be exposed to the virus. Four percent is as good (or bad) as nothing.

The researchers point out that the study was not designed to look at these differences, but call the results “intriguing”. To an immunologist, they must be. Perhaps the immunity conferred by the vaccine is not strong enough to withstand the repeated assaults suffered by someone who shares needles daily or turns tricks three times a week — I have no idea. But to public health workers, it is not intriguing, it is devastating. If a vaccine doesn’t work for the people who need it most, what’s the point? It depends on costs, of course. But would we really develop something that we could give to people who have a very low probability of exposure, while leaving those who are likely to be at risk for HIV unprotected?

It’s a false dichotomy, of course. This trial is a triumph for basic science, because it gives us something positive to work with. It is very far from being a triumph for public health, and it is not helpful that in the early rush of euphoria it was presented as such. I’d even be wary of the language used by the authors of the NEJM paper: in their headline result, they reported quite wrongly that the study showed that “there was a trend toward the prevention of HIV-1 infection among the vaccine recipients”. A trend is something that develops over time. If anything, the data suggest that the effect of the vaccine was weakened over time, so the trend was away from protection, not towards it. But I’m splitting hairs. With vaccines, the basic science has to be right before we even think about the public health questions. This study will send the immunologists back to the drawing board. They need to figure out how we have a possibly succesful vaccine that makes no difference to viral loads in those who do get infected. They need to understand why people who are most exposed to HIV are least likely to be protected. They need to parse out the mechanism by which these two sets of shots, each of which has failed on its own, might be working together. If (and it is still only an if) they can do all of that, then develop something that really does work, the public health nerds can start worrying about how to deliver it, and to whom.

Today’s post is copied wholesale from Laura Agustin. In the poster, the product of a workshop by the Thai sex workers rights organisation EMPOWER, sex workers relate what being “rescued” in brothel raids means to them.

• We lose our savings and our belongings.
• We are locked up.
• We are interrogated by many people.
• They force us to be witnesses.
• We are held until the court case.
• We are held till deportation.
• We are forced re-training.
• We are not given compensation by anybody.
• Our family must borrow money to survive while we wait.
• Our family is in a panic.
• We are anxious for our family.
• Strangers visit our village telling people about us.
• The village and the soldiers cause our family problems.
• Our family has to pay ‘fines’ or bribes to the soldiers.
• We are sent home.
• Military abuses and no work continues at home.
• My family has a debt.
• We must find a way back to Thailand to start again.

Many of these women are Burmese. They’ve worked hard to get to Northern Thailand, and their hard work while they are there is often a mainstay for their families. For me, the most telling of their comments is the last: after going through all of the nightmares associated with being “rescued” from a life selling sex, they have to start again from scratch. That means paying more bribes to get across the border, more jostling to get back into pole position at the brothel. It must be a consolation to the anti sex-work organisations that for the time between their rescue and getting back to work, at least, the souls of these women are safe.

Among anti sex-work organisations, some would include the Poppy Project, the originators of a somewhat lurid it’s-all-about-trafficking view of the London sex scene was featured on IRMA recently. I’ll let friends and colleagues who are closer to the London trade than I am respond to that more fully.

Thailand’s relative neglect of HIV prevention among gay men has been confirmed yet again by a new paper to be published in the upcoming edition of JAIDS — the abstract is on line now. (JAIDS is one of those dinosaur journals which still makes you pay for access to the full text.) Using blood samples taken between 2006 and 2007, researchers in Bangkok used a relatively new technology to find out which infections were recent at the time people came in for their voluntary test.

Nine of the 11 incident infections were in men, and 60% were in gay men. Overall, the rate of new infections was equivalent to 2.7% a year. This sort of testing is imprecise at best, not least because it depends on who walks in the door asking for a test. But still, it’s worrying that such an overwhelmingly high proportion of the newly infected are among gay men. To make matters worse, the data probably exclude many of the highest-risk gay men in Bangkok, who go to gay and sex-worker friendly clinics, one improbably based in Bangkok Christian Hospital, just a sound-system’s reach from the flesh-pots of the Patpong red light district and Silom Soi 4, it’s gay equivalent.

The concentration of new infections among gay men led the researchers to conclude that these boys would be a good study population for new HIV infections in Thailand. So at least the junkies — who have long been study-population of choice for Bangkok’s talented pool of AIDS epidemiologists — may get a break for a while.

Meanwhile, over in Beijing, colleagues of mine from China CDC used a slightly different but also relatively new method to look at new HIV infections among gay men. Because the Chinese Medical Journal is not a dinosaur, you can read the full text online. They actively recruited gay men to the study; many people signed up through internet sites or because they were contacted in bars and clubs; you’d expect these guys to be at the higher end of the risk spectrum. And they are. My mates estimated new infections at 2.9% in 2005 and 3.6% in 2006. About the same as among gay men in London, in fact.

A McDonald’s in every airport, a Starbucks on every block, and a hear-no-evil, see-no-evil, speak-no evil HIV crisis in the gay community. Thailand and China look more like the US and Britain every day.

Meanwhile,

Their discussion about the rights and wrongs of discrimination in toilets is interesting. But the “where to pee” debate masks something (to me) much more important: “where to go for health care”. When I was working with the fabulous Lenny Sugiharto and other waria in Indonesia, I learned that one of the reasons these “women with penises”/”other definition of your choice” had such phenomenally high rates of untreated STIs and other illness was that they HATED going to health services, and getting stuck in the men’s wards. Groups like Arus Pelangi are lobbying for less discriminatory attitudes among service providers, but there’s a hell of a long way to go.

The Ministry of Public Health is concerned that young men are going through the cheap, easy castration process before they’ve really thought through the implications of this extraordinarily irreversible process. The debate around the ban has raised an issue that I’ve been thinking about for a while. Will the world of transgenders (katoey in Thailand, waria in Indonesia, hijras in much of the Indian subcontinent) morph as an open gay scene emerges? The subculture differs quite a bit from country to country — in Indonesia, most waria keep (and regularly excercise) their male tackle, even as the live as women, selling sex to straight men. In Thailand, far more katoeys go through the whole sex change process — castration is a first step which cuts down on hormone bills until the wallet is full enough for the full chop. But whatever the local norm. living as a transgender has been an obvious path for many people who, as young men, were effeminate or confused about their sexuality.

That was in part because there was virtually no visible gay scene. That’s now changing very rapidly throughout Asia. Young men, including those from rural areas and less educated backgrounds, are going on line and discovering that there’s a gay community in a city not far away. Are some of these men people that would in an earlier age have become transgenders? We’ll never know, but it does seem to me that delaying castration until a young man has had a chance to explore some of the alternatives for sexual expression is not such a bad idea.

Re the photo: I ripped it off a random website, which ran the credit: A woman (left) chats with katoey at a Bangkok cafe Flickr photo by Bart Morane. But the woman (left) looks for all the world like my friend Yindee, a former UN bureaucrat and therefore more than likely to be hanging out in bars chatting to katoey.

This video, not to be taken tooooo seriously (though the science is spot on), is the product of a rainy afternoon with the incomparable Candy Gourlay. Check out Candy’s wit, wisdom and illustration at Notes From the Slushpile

One in four Bangkok teens said they’d be celebrating Valentines day by having sex, according to a poll carried out by Bangkok’s Assumption University. This, says a Reuters report has stung the authorities into action. The floodlights will be on in the parks, and The Powers That Be will be policing the city’s motels to break up canoodling couples.

I note that the poll came from one of largely Buddhist Thailand’s few Catholic universities. According the The Nation, the survey covered 1,159 kids aged 12-18. Catholic sites worry about the apparently casual attitude to sex, while others think the church should stay out of sex. My question is this: if only one in four intend to have sex on Valentine’s day, what do the other three in four intend to do?