Are we about to eliminate AIDS?
WHAT if we could rid the world of AIDS? The notion might sound like fantasy: HIV infection has no cure and no vaccine, after all. Yet there is a way to completely wipe it out – at least in theory. What’s more, it would take only existing medical technology to do the job.
Here’s how it works. If someone who is HIV positive takes antiretroviral-drug therapy they can live a long life and almost never pass on the virus, even through unprotected sex. So if everyone with HIV were on therapy, there would be little or no transmission. Once all these people had died, of whatever cause, the virus would be gone for good.
It’s a simple idea, but the obstacles to implementing it worldwide are enormous. Persuading everyone with HIV to start therapy purely for public health reasons could be ethically dubious. To identify everyone who is HIV positive would require such widespread testing that some may feel it breached their civil liberties. Then there is the question of who would fund such a massive undertaking.
Yet the idea of eliminating HIV is so appealing, and the benefit to humanity so huge, that scientists and policy-makers are seriously considering the concept, albeit on regional scales. In the next few months the World Health Organization (WHO) will meet to discuss how the idea could be tried in developing countries, and something approaching elimination might be attempted in the UK within the next decade. “You could eliminate transmission overnight,” says Marcus Conant, an HIV specialist in San Francisco.
A plan like this can only be countenanced thanks to some sweeping changes over the past decade in the way HIV is managed by doctors and viewed by the public. In 1985, when HIV testing began, no treatment for the virus existed, so a positive result was effectively a death sentence. Fear of the virus and the fact that it spread most easily among gay men and intravenous drug users meant people with HIV were shunned, as well as being barred from taking out health and life insurance. The decision to have the test was generally an agonising one and many decided it was better not to know.
It was not until the mid-1990s and the arrival of cocktails of antiviral drugs that people with HIV could begin to imagine surviving for any significant length of time. Fear of the virus subsided and public attitudes began to soften. The beauty of these cocktails lies in the combination of drugs. If just one drug is taken, HIV can mutate and become resistant to it, but with three drugs the virus would need three simultaneous mutations to become resistant, a highly improbable event. This “triple therapy” stops viral replication in its tracks and seems to hold AIDS at bay indefinitely. People now had every reason to take the test.
If treatment for the virus has changed dramatically, so too has treatment timing. HIV progression is gauged by measuring levels of CD4 cells – immune cells that the virus infects and kills. A typical healthy person has more than 500 of these cells per microlitre of blood, while someone with HIV sees their count gradually fall. Once their CD4 count falls below about 200, the immune system can no longer fight off common pathogens, leading to “opportunistic” infections such as pneumonia and thrush.
In the early days, doctors tended to delay triple therapy until a patient’s CD4 count had dropped to about 200, on the basis that this would catch most people before opportunistic infections struck. There were good reasons not to start treatment sooner: the first antiretrovirals had nasty side effects and involved taking up to 20 tablets a day. What’s more, at a time when only a few antiretrovirals existed, it was a real concern that if drug resistance developed, an individual could run out of medicines to take. Today, these obstacles have largely disappeared: people on the latest regimens take only one or two pills a day with few side effects, if any, and there are two dozen drugs to choose from.
We know now that starting treatment earlier than at a CD4 count of 200 brings health benefits. As well as reducing the risk of opportunistic infections, a large study showed last year that people who began treatment with a CD4 count above 350 are less likely to develop conditions usually seen as unrelated to HIV, such as heart or kidney disease (The Journal of Infectious Diseases, vol 197, p 1133). Researchers now suspect that long-term HIV infection causes a low-level activation of the immune system that can damage the heart, kidneys and liver. For these reasons, the treatment threshold in wealthy nations is now 350.
Of course this can only happen if someone has been diagnosed, something that often happens dangerously late. In the west, about one-quarter of people with HIV only discover their status when they are admitted to hospital with an opportunistic infection or cancer. Some die before triple therapy can take effect – from pneumonia, for example.
It is the benefits of early treatment, combined with the perils of late diagnosis, that have convinced many doctors and patient groups to urge that HIV tests be used more widely. For example, last year the UK government’s Health Protection Agency endorsed guidelines saying that in urban areas of the UK where people with undiagnosed infections are likely to be concentrated, HIV tests should be more widely available. In these places, everyone from 15 to 60 should have the test routinely when they register with a primary care doctor or are admitted to hospital. “We want normalisation of testing,” says Barry Evans, an epidemiologist at the HPA. “They should get tested like they get their blood pressure checked.”
Earlier HIV diagnosis not only helps the infected person, it also benefits everyone else. Once someone knows they are HIV positive, they are less likely to pass the virus to others through unsafe sex or sharing needles. The really important factor, though, is that therapy stops viral replication, so that much less virus reaches an infected person’s bodily fluids.
Just how much this reduces the risk of transmission is a matter of great debate. Most of the evidence comes from studies of monogamous heterosexual couples who are “serodiscordant” – in other words one person is HIV positive and the other is not. Some studies have found a transmission rate of zero, but only in people who scrupulously take their tablets, so that no virus is detectable in their blood, and who are free of other sexually transmitted infections.
No condoms needed
Last year, a group of HIV specialists on the Swiss government’s AIDS commission (EKAF) announced that HIV-positive people who met these conditions were “sexually non-infectious”. For the first time serodiscordant heterosexual couples got official approval to bin their condoms. Other experts disagree with the Swiss decision, pointing out that the virus can sometimes be found in semen and vaginal fluid even if it is undetectable in blood. Also, as the research results come from straight couples, it is unclear how the advice applies to gay men. Despite these doubts, some doctors now see patients with normal CD4 counts asking to start therapy purely to avoid passing on the virus.
While it is debatable just how small the transmission risk really is, it is indisputably much lower for patients taking antiretroviral therapy than for those who are not. That has led researchers to start speculating about expanding testing and treatment to everyone with HIV. In November 2008, a paper published in The Lancet, written by five of the WHO’s leading AIDS specialists, drew the widest attention so far (vol 373, p 48).
The researchers looked at the case for elimination in South Africa, which has the highest number of HIV cases in the world. They modelled what would happen if everyone over 15 were given annual tests, with all those who tested positive offered free antiretroviral treatment immediately, regardless of their CD4 count. They plugged in actual figures from a free treatment programme in Malawi to factor in people who decline therapy, stop because of side effects or switch drugs because of resistance.
The team found that within 10 years, the scheme would slash new HIV infections from the 1 in 50 people at present to less than 1 in 1000. Within 50 years, as people with HIV died (mainly from other causes), prevalence in the general population would fall from about 10 per cent to less than 1 per cent.
That all sounds great, but the cost of the scheme would initially be about $3.5 billion a year. That might sound prohibitive, but the key comparison to make is with the cost of alternative plans. Today, aid programmes can fund antiretroviral treatment for only about one-third of people in the developing world with a CD4 count below 200. All the major HIV organisations, such as UNAIDS and the WHO, and several western governments including the UK’s, are now calling for universal access to therapy, by which they mean getting the drugs to everyone with a count below 200. Some want the threshold to be raised to 350 in the developing world too.
However, the problem with this form of universal access is that it would do little to curb transmission, because everyone with CD4 counts above the threshold would still be spreading the virus. The cost of such a scheme would almost certainly rise over time as more people became infected, unlike the WHO experts’ more ambitious scheme. “The [elimination] strategy becomes cost-saving in the future, despite initially increased costs,” says Kevin De Cock, director of the WHO’s HIV/AIDS department and one of the paper’s authors. By 2030 it would become cheaper than using a 350 threshold (see graph).
The idea is still very much in its early stages, with De Cock stressing they are “not suggesting a change in policy but stimulating a discussion”. In the next few months, the WHO will bring together scientists, policy-makers and funders to discuss employing the strategy in developing countries.
In some ways it might be easier to attempt universal treatment in a developed country. For example, the UK could, if it chose, afford to put every one of its estimated 73,000 HIV-positive residents on antiretroviral therapy. On the other hand with HIV only affecting 0.1 per cent of the UK population, universal testing would be hard to justify. The modelling from The Lancet paper would have to be redone for the UK, where, unlike in South Africa, transmission is primarily among gay men. (Cases among heterosexuals are rising; these are mainly immigrants who have caught the virus abroad.) “We’re trying to focus more on certain population groups or areas,” says Tim Chadborn of the HPA.
Conant, however, argues that testing everyone would help to further reduce the stigma around AIDS. HIV may no longer be an automatic bar for health insurance but there is still an image problem for a disease that in the west is still seen as affecting mainly gay men, immigrants, prostitutes and drug addicts. Conant advocates mass testing in the US at churches and meetings of professional groups such as doctors – as happens today at gay bars. “It has got to be universal,” he says.
Mass HIV testing at churches and meetings of professionals such as doctors would reduce stigma
Perhaps the most medically contentious part of the elimination plan, in any country, is that all those diagnosed positive would begin antiretroviral treatment immediately. At present there is no firm evidence that HIV does any damage to an individual as long as their CD4 count is above 350. “There are great big ethical problems about recommending treatment to someone when it’s not clinically beneficial to that person,” says Chadbourn.
Sex abroad
Still, no one really knows what the effects of starting treatment earlier are. This question should be answered by a large international trial called START, organised by the US National Institutes of Health, to compare the health of people who start therapy at 350 with that of people who start at over 500. The results will not be in for six years, though.
If the people in the over-500 group do best, the main medical objection to elimination disappears. “If we can establish that there’s a benefit, I would imagine that we would try to do exactly what’s being proposed in The Lancet paper,” says Andrew Phillips, an epidemiologist at the Royal Free and University College Medical School in London who is involved in START.
If a western country introduces widespread testing and immediate treatment, new infections should dwindle. “If there are benefits for the individual and benefits for the population, I would very strongly support that,” says Evans. He would contemplate elimination even if the over-500 group in the START trial does no better than the 350 group, as long as it does no worse.
Perhaps the biggest obstacle would be the importation of HIV from abroad. The HPA now recommends that migrants from countries with high HIV rates be offered a test when they access any health service, such as registering with a primary care doctor. The agency frowns on testing at ports of entry in case it encourages discrimination.
Residents also import HIV by having unsafe sex while abroad. People would have to be persuaded to take the test when they returned. For Brian Gazzard, one of the UK’s leading HIV specialists, based at the Chelsea and Westminster Hospital in London, this makes elimination on a country-by-country basis unfeasible. “It’s got to be done worldwide,” he says. “A public debate about that issue would be wonderful.”
Western countries without state-funded healthcare would hit bigger problems. In the US, for example, many people with HIV delay starting therapy because they pay part or all of the cost. “The government would have to pay,” says Conant.
Treatment standards would also have to improve in the US. Some health insurers insist that patients see primary care doctors rather than more expensive specialists. According to Conant, some non-specialists fail to use drug regimens that totally block viral replication, so the virus can still be transmitted. “That’s the most common mistake I see,” he says.
There are many obstacles to be overcome if any form of elimination plan, national or global, is to be attempted. Yet the damage done by AIDS is so huge that the chance to rid just some places of it has to be worth considering.
What is certain is that, however and wherever it is attempted, such a scheme will be controversial. Hard-line religious groups that view AIDS as divine retribution are unlikely to help out. Some liberals, on the other hand, might resist the idea of mass testing. “Should we try a social intervention which infringes on people’s civil liberties?” asks Conant. “AIDS infringes upon people too. If we’re going to stop this epidemic, this is a responsibility that society has to shoulder.”
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