
IT COULD be the end of AIDS as a global epidemic. Antiretroviral drugs that block the spread of HIV are about to transform the battle against AIDS and in theory could even eliminate HIV from some parts of the world. 鈥淭his is a watershed,鈥 says at the University of California in San Francisco. 鈥淲e can now envision a world where HIV infection becomes rare.鈥
聯This is a watershed. We can now envision a world where HIV infection becomes rare聰
Excitement is high in Rome, Italy, this week, which is playing host to the , which kills almost . Delegates will hear the first detailed evidence that antiretroviral drugs (ARVs) not only help those infected with HIV to stay alive but also stop the virus spreading in two ways.
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The first approach is called pre-exposure prophylaxis (PrEP). Two independent groups working in Africa have announced that putting uninfected heterosexual people on low doses of ARVs reduced their risk of catching HIV by 63 to 68 per cent 鈥 on just one 25 cent pill a day. A constant level of ARVs in the bloodstream kills the virus before it can establish an infection, preventing HIV from taking hold. This worked for both men and women 鈥 the hardest group to protect in Africa partly because many are pressurised into having unsafe sex. 鈥淸The results are] really exciting, just super,鈥 says Catherine Hankins, chief scientific adviser to UNAIDS 鈥 the Joint United Nations Programme on HIV and AIDS.
Another major study using 鈥渢reatment as prevention鈥 (TasP) has had great success in giving ARVs to infected people earlier than usual, before the virus has destroyed many white blood cells. In a trial which covered 13 countries and involved 1763 heterosexual couples, early intervention with ARVs reduced the spread of HIV to uninfected partners by a massive 96 per cent.All the studies were halted early so the placebo groups could get the real treatments.
聯Early intervention reduced the spread of HIV to uninfected partners by a massive 96 per cent聰
To put these approaches into practice, we will need cheap and plentiful ARVs. A groundbreaking deal struck last week may solve the problem (see 鈥淐heap drugs for those in need鈥 right).
鈥淲e now have a powerful package of preventive measures. We didn鈥檛 have that a week ago,鈥 says at the University of Washington in Seattle, leader of one of the . This is welcome news since HIV is spreading 2.5 times as fast as people are put on ARVs.
鈥淣ow the question is how each country should roll each of these measures out,鈥 says Baeten. That is tricky, as it means giving powerful drugs to two new groups, people who are uninfected or have yet to develop symptoms. Advocates of TasP worry that HIV-negative people, who vastly outnumber those with HIV, even in Africa, will consume limited supplies of ARVs that could otherwise be used to treat infected people. Baeten says PrEP should therefore be targeted at high-risk groups 鈥 sex-workers, vulnerable young women, uninfected partners of HIV carriers and men who have sex with men.
Drug resistance could be a problem, though. Infected people take three different ARVs to stop the virus becoming resistant; taking just one or two leads to resistance in six months. Uninfected people on PrEP get one or two ARVs, so they must be virus-free. The trouble is the tests are not always accurate: one person on PrEP in the African trials was already infected, and developed resistance.
PrEP is not 100 per cent effective either, especially as healthy people are more likely to forget their medicine than those with symptoms. So people on PrEP must be repeatedly tested, and switched to three-drug treatment if they do become infected, says Grant, who successfully tested PrEP in homosexual couples in the US last year. Long-lasting drugs that do not need to be taken every day are being developed, which could make compliance easier.
Jonathan Weber of Imperial College London, isn鈥檛 convinced. 鈥淚 can鈥檛 see how on earth the benefits of PrEP can outweigh the detrimental aspects,鈥 he says. Weber is concerned that PrEP may change sexual behaviours for the worse. Computer models suggest PrEP can increase the spread of HIV if just 15 per cent of users feel protected enough to dispense with condoms.
Both Baeten and Grant are watching their study groups to see if that happens. Grant is optimistic. 鈥淎lmost every prevention study has shown that if you use one method, it increases use of other ones too, possibly because there鈥檚 increased awareness of the value of prevention.鈥 Indeed, studies have shown that circumcised African men increase their condom use.
With TasP, infected people start taking ARVs before their white blood cells fall below 350 per microlitre of blood, while they can still block viral spread; the ARVs then take over by cutting blood levels of HIV. Besides cutting transmission, Myron Cohen at the University of North Carolina at Chapel Hill reported this week that this led to healthier HIV carriers, with fewer cases of tuberculosis The New England Journal of Medicine ().
Being on ARVs for so long also leads to drug-resistant virus, however. Instead, they might lower HIV levels with a vaccine: this week , a London-based company, announced that its vaccine cut blood levels of HIV in 55 carriers by 90 per cent.
At the extreme, TasP could even roll back the global HIV epidemic. In a mathematical model, testing everyone for HIV then immediately treating anyone who is positive cut transmission enough to eliminate the virus from some populations, says Chris Dye of the WHO.
It鈥檚 not PrEP versus TasP, says Baeten. Combining all approaches 鈥渃ould have an effect much greater than the sum of what each could achieve separately鈥.
The key is to target them right, depending on the local HIV situation. The question of where to start the onslaught is a debate that is just beginning in Rome.
Cheap drugs for those in need
Rolling back AIDS with antiretroviral drugs that attack HIV will only work if cheap and plentiful supplies are available. As people develop resistance to the old drugs, they will need newer versions. But those are usually under patent, and too expensive.
Last week, though, there was a breakthrough: California-based pharmaceuticals firm reached an agreement with the UN-backed Medicines Patent Pool, based in Geneva, Switzerland. According to the deal Indian firms that make generic drugs will be allowed to make cheap copies of four important ARVs, including three new, patented ones. The drugs will go on sale in more than 100 poor countries.
In 2001 poor countries won the right to make such deals themselves, but few have, partly due to political pressure from industrialised countries, which have imposed numerous hurdles to limit the number of deals going through.
The patent pool aims to break the deadlock. Its head, Ellen鈥檛 Hoen, says that once Indian generics firms know they will be licensed to sell the product, they can start investing in the production facilities. Gilead won鈥檛 even lose any sales: buyers of generics couldn鈥檛 have afforded its patented product. Of the nine remaining holders of ARV patents, six are in 鈥渟erious discussion鈥 with the patent pool, she says. Only Johnson and Johnson, Merck and Abbott are so far holding out.
Only 36 per cent of people with HIV in poor countries now get treatment. Meeting the UN pledge to double that number by 2015 will mean doubling the amount of ARVs available. The same amount again will be needed to treat those people earlier in the infection, to prevent spread of the virus (see main story).