Tuesday, June 7, 2011

AIDS, The 30 Years War

IT WAS not quite a birthday present, but it was pretty close. On May 12 Network (HPTN), an international research collaboration, announced that its most important project was being terminated—not because it had failed, but because it had succeeded. The study, led by Myron Cohen of the University of North Carolina, Chapel Hill, had looked at 1 ,763 couples, most straight, some gay, from Africa, Asia and North and South America, in which one partner but not the other was infected. All were counselled in safe sex, given free condoms and offered regular medical check-ups. In half, the infected partner was also offered anti- retroviral drugs, even though he or she did not show actual symptoms of AIDS and would thus not normally have been treated. Over the course of six years there were 28 cross-infections. Of those, only one was in the group receiving the drugs. On June 5 th, a little over three weeks after HPTN’s announcement, AIDS will be 30 years old—or, more accurately, it will be 30 years since America’s Centres for Disease Control and Prevention reported a cluster of unusual infections in Los Angeles that were the first medically recognised cases. On June 8 th a meeting of the United Nations’ General Assembly, expected to be attended by 40 heads of state and government, will discuss progress in fighting the pandemic and wrestle with the question of what to do next. HPTN052 , as the trial in question is known, points the way. What HPTN052 shows is that the drug treatment used to prolong the lives of those infected with HIV, by stopping the virus reproducing in their bodies, can also stop the virus’s transmission. It might therefore be the key to bringing the pandemic under control. The crucial word is “might”. People do not like taking medicine, particularly if they have no symptoms. And drugs cost money. The war on AIDS has done well, financially, over the past decade (see chart 1) , but people are feeling the pinch and the cash is no longer increasing. That is ironic, as there are now several clear ways of attacking the problem, above and beyond the usual exhortations of chastity, fidelity and condom use. It is no time to give up the fight. The past decade has seen real progress. Though it is true that there are two new infections for every new person put on anti-retroviral drugs, and that AIDS is killing 1.8 m people a year ( see chart 2) , it is also the case, according to UNAIDS, the United Nations agency responsible for monitoring and combating the disease, that 6.6 m people in low- and middle-income countries are on such drugs, and that the rate of new HIV infections in 33 poor countries has fallen by a quarter or more from its peak. In 2001 the number on drugs was trivial (see chart 3) and the peak number of deaths, in 2005 , was 2.1 m. At the moment, only those showing symptoms of AIDS, or whose level of a crucial immune- system cell has fallen below a certain threshold, are offered treatment. Even so, there are reckoned to be about 9 m people who need treatment but are not receiving it. Add those who have no symptoms and that becomes about 27 m. At $100 for a year’s course of the drugs, plus around $400 for the cost of administration, they would need a lot of money. In 2010 , according to UNAIDS, the world spent $16 billion on the epidemic. Treating all 34 m people infected might mean almost doubling that. New balls, please Prevention by treatment is, nevertheless, a heady prospect. Indeed, Michel Sidibé, UNAIDS’ s boss, thinks the result of HPTN052 is “a game changer” . It would be a long game. Not only would anti-AIDS drugs have to be made available to everyone infected—so- called universal access, which is a UN objective, and which the organisation hopes might be achieved by 2015 —but all those people, or, at least, the vast majority of them, would have to be persuaded to take them. That is difficult enough when someone is ill. The latest report from UNAIDS * suggests that almost one in five of those put on the drugs stops taking them within a year. It will be even harder to persuade the asymptomatic to pop a daily pill or two for the public good. They might do so for love, of course. More selfishly, one result of HPTN052 in those receiving drugs was less tuberculosis, a disease that is a common consequence AIDS. So people now thought symptomless may not be quite as symptomless as they seem. Indeed, in 2010 the World Health Organisation raised the immune-system threshold below which drugs are offered by 75 %. That is a step on the way to offering the drugs to all infected people anyway. Nor is treating the infected, whether for their own good or for the good of others, the only approach being investigated. Several trials have shown that circumcision is a good way to stop men catching the virus. It can reduce the risk by about 50 %, and the message has got out. The rate of circumcision in Africa is rocketing. Attempts to protect women, by developing vaginal microbicides that destroy HIV in infected semen, have been less successful. Initial trials using a seaweed derivative failed, and might even have made things worse. But a trial using a drug called tenofovir had promising results, reported last year, and further tests are going on at the moment. Moreover, there is already one well-proven way of stopping the virus’s transmission using drugs. This is between mothers and children at birth. Even a single dose of another drug, nevirapine, halves the risk of an infected mother passing the virus to her baby. More extensive courses can reduce the risk by 90 %. There are also the good-old standbys, behaviour change (a euphemism for less promiscuous sex) and condom use. Here, the data are equivocal. As might be expected, the message is getting through in some places, but not in others. In South Africa, for example, according to UNAIDS, 77 % of men and 68 % of women reported using a condom last time they had sex. In 14 other high-prevalence countries, though, more than 70 % of both sexes reported that they had not. The armory, in other words, is getting fuller. But war costs money, and money is in short supply at the moment. The first UN meeting on AIDS, held ten years ago near the 20 th anniversary, catalysed the formation of the Global Fund ( which also has tuberculosis and malaria in its remit) and that, in turn, led to the United States President’s Emergency Plan for AIDS Relief ( PEPFAR) created by George Bush junior. No one likes to be seen as mean and so, in a decade of rising prosperity, politicians put their hands in their taxpayers’ pockets and donated generously to the cause. This time, the atmosphere is different. It is still the case that no one wants to be seen as mean, but the game of chicken is now the other way round. Then, each act of generosity made it harder for others to refuse. Now, each withdrawal from the fray makes another’s easier. Many of the biggest donors to the Global Fund, including America, Britain, Canada, France and the Scandinavians, are still committed (Japan’s position, in light of the recent earthquake and tsunami, is unclear). But the Netherlands and Spain have announced cuts. Germany (and also Spain) are delaying their payments during a review of the fund’s auditing procedures. (The review, ironically, is a result of those procedures being uniquely transparent for an international aid agency, and thus highlighting shenanigans in a few recipient countries that might otherwise have remained buried.) And one country, Italy, has simply stopped paying its pledged contribution without explanation.There is also dark talk of several countries trying to water down the language of the declaration that the UN meeting is expected to issue, so that it no longer has numerical targets with specific dates. In a time of austerity, then, value for money is even more important than it might otherwise be. A group of researchers led by Bernhard Schwartländer, director of evidence, strategy and results at UNAIDS, have therefore put their minds to how to spend what is available most wisely. Dr Schwartländer and his team looked at ten approaches to treating and preventing AIDS, ranging from drugs, via intervening in the prostitution industry, to searching for joint savings by collaborating with other areas of international development. They then devised a computer model that attempted to show how these would play out in each of 139 low- and middle-income countries. The result ( see chart 4) is that expenditure peaks at $22 billion in 2015 , and drops below $20 billion in 2020. If Dr Schwartländer and his colleagues are right, therefore, the world (and this includes at least the middle-income members of the 139) needs to stump up a maximum of $6 billion more at the peak of things than it is doing now. Moreover, this extra money would, according to Dr Schwartländer’s sums, largely be offset by savings on treatment avoided—for, compared with business as usual, 12. 2 m infections would be averted, and 7. 4 m deaths.Game, set and match? There are even a few ambitious scientists who talk not just of treatment, but of cure. Exactly how this would be done induces a flurry of arm- waving, but their reasons for believing it is theoretically possible—and thus worth investigating—are that about one infected person in 1 ,000 is now known to control the infection naturally and never develop symptoms, and that several studies have identified antibodies that appear to neutralise HIV. This suggests that boosting the immune system with an appropriate vaccine, or developing appropriate antibodies for injection as a drug, might be possible. Certainly Bertrand Audoin, the executive head of the International AIDS Society, thinks so. He, and people like him,