Fight against Aids is at turning point

Fight against Aids is at turning point
By Andrew Jack
Published: May 30 2006 19:35 | Last updated: May 30 2006 19:35. Copyright by The Financial Times

As leaders of nations corroded by Aids gather at the United Nations in New York on Wednesday to discuss the disease, another group will be noticeably absent: leaders of the world’s richest nations who pledged them significant help five years ago.

The continued ambivalence – even as public health experts are heralding the first tentative signs of a slowdown in the growth of Aids since it was identified in 1981 – reflects both the enormity of the task ahead and the political and ethical sensitivities that underpin it.

To consign Aids to history will require not only a big injection of cash over the long term. It will also demand a consensus on how best to distribute resources between prevention, diag nosis and treatment – and a new boldness in tackling the issues that debate will throw up.

Peter Piot, head of UNAids, the United Nations’ co-ordinating body, reflects the mood of cautious optimism that has taken hold among experts in recent months. “There has been more progress in the last two years than in the previous 22,” he says. “In 1996, even working on Aids was stigmatising, let alone having it; 2005 was the least bad year yet.”

On the positive side, science has made considerable progress in treating Aids through the development of antiretroviral medicines, and politicians have mobilised strong support to secure additional funding. Last July, the leaders of the G8 leading industrialised nations pledged at Gleneagles to achieve “as close as possible” to universal treatment for those who needed it by 2010.

Spurred on by the previous UN General Assembly on Aids in 2001, the Global Fund to Fight Aids, Tuberculosis and Malaria was created. It has since become the biggest channel for multilateral support.

Richard Feachem, its head, says: “It’s quite remarkable. Since our creation in 2002, we have committed $10bn to projects in 130 countries and the impact is now starting to be seen.”

Total support has risen substantially to more than $8bn a year, swollen further by the World Bank, bilateral programmes led by US President George W. Bush’s Pepfar and redoubled efforts by individual countries.

There has also been a sharp drop in the price of drugs, through a mixture of discounts and donation programmes by pharmaceutical companies, price competition from copycat generic manufacturers and political leverage from groups such as the Clinton Foundation.

Mr Piot can point to findings in the latest UNAids report published on Tuesday showing more than 1.3m HIV- positive people in low- and middle-income countries are now on treatment, up from 240,000 five years ago.

But it is far too soon to claim victory. Aids remains one of the world’s greatest health threats, responsible for 25m deaths since 1981. It has attacked teachers, doctors and all parts of the workforce, while creating hundreds of thousands of orphans, undermining economic development and even threatening global security.

While 700,000 people are on treatment in the developed world – a high proportion of those who need it – the 1.3m in the developing nations represents only one-fifth of those with advanced HIV who should be on drugs. Nearly 3m people died from Aids last year, including hundreds of thousands of children unable to gain access to little-researched paediatric drugs.

More worrying still, the number of new HIV cases was at its highest level ever in 2005 at 4m, while the life- prolonging effect of drugs means that a record 40m people are now living with the infection.

Against such a background, there is no doubt that more money is required. “The world is on a trajectory that will fall significantly short of the inter nationally endorsed universal access goal for 2010, leaving millions without life-saving care,” warns the International Treatment Preparedness Coalition, one advocacy group.

The failure of the World Health Organisation’s goal of “3 by 5” – or 3m on treatment by the end of 2005 – highlighted the challenges. Meeting the goal of universal treatment would mean placing and keeping up to 10m people on treatment by 2010. UNAids estimates that that will cost $23bn a year for at least a generation, or three times current spending levels.

“We are at a real turning point in the balance between optimism and despair,” says the Global Fund’s Mr Feachem. “Without full funding, the G8 pledge is just pie in the sky.”

He is forced to seek fresh support from donor countries every few months, with the latest “sixth round” recently launched with support from the UK, which is keen to see follow-through from the Gleneagles’ G8 summit it hosted last summer. Other countries were more hesitant and little of the money has been raised so far.

“Up till now, it has been about haphazard crisis management,” says Mr Piot. “Now we are starting to have a critical mass, we need a more sustainable, strategic, long-term response. The reality of dealing with Aids is it is not something we can run year by year. We need to count in decades.”

Business could do much more. For Jim Kim, the former head of the WHO’s 3-by-5 programme, that includes drug manufacturers. He believes they should sub-contract antiretroviral production to low-cost producers.

“We’ve got to get serious about establishing a humanitarian corridor,” he says. “There is no way discount programmes will meet the target of 8-10m people on treatment by 2010.”

Richard Holbrooke, president of the 215-strong Global Business Coalition on HIV/Aids, called this month for support from many more companies. They can help not only through donations, but by enhancing their own activities in offering education, testing, counselling, treatment and a pledge of non-discrimination to employees and their families.

Beyond new money, however, a second issue in the fight against Aids is how the funds should be spent. The G8 leaders, the WHO and the UN assemblies have focused primarily on accelerated treatment. They have been far less vocal about prevention and HIV-testing programmes, which lack the dramatic appeal of “saving lives now”.

Yet both drugs, and the infrastructure required to ensure people receive them consistently, mean that treatment is costly and risks diluting other health initiatives in poor countries. Prevention and testing may prove cheaper, less disruptive and more effective in tackling the causes of the epidemic.

“An increased emphasis on prevention is something that is sorely needed,” says John Tedstrom, president of Transatlantic Partners Against Aids, a charity working in the countries of the former Soviet Union to raise the profile of the issue at this year’s G8 summit in St Petersburg.

While there are some indications from UNAids that infection rates may have begun to fall in parts of Africa where they had reached saturation point, he stresses that in other regions of the world – notably Russia, China and India – the situation remains parlous. The prospect of treatment may have induced complacency that has in turn led to new infections in the US and western Europe.

Treatment on its own in any case does little to address the longer-term problem of stemming the rate of infection. The more survive thanks to antiretroviral drugs, the larger the pool of HIV-positive people. That, in turn, risks further spread of HIV – including a drug-resistant form of the virus – to others.

“If you have treatment but it’s in effective and generating resistance, you are building up a problem for the future that is going to be almost insoluble,” warns Richard Coker, reader in health at the London School of Hygiene and Tropical Medicine. “Personally, I would be more cautious than the international community in advising that ‘antiretrovirals for all’ is feasible and will achieve the claimed benefits. If this doesn’t work, we won’t get another opportunity to revisit it with the same sense of urgency and support.”

Most health officials are reluctant to argue for a reallocation of scarce resources. “The great lesson of the last couple of years is that there are no choices,” says Mr Feachem. “We need prevention, testing and treatment: all three, all big, all together. They feed off each other.”

Experience in the field certainly suggests that the best way to ensure people are tested for HIV is to offer them the incentive of treatment. Testing also provides an opportunity to reinforce prevention messages.

Yet if prevention and testing have been underplayed, even more neglected has been research into what works. Information on the extent and spread of drug-resistant HIV virus in the developing world is scant, for instance. The Global Fund is only now scrambling to commission a five-year evaluation of its own work and cannot even detail how its money has been split between prevention, treatment and testing.

“We don’t have the evidence of the effects on the rest of the public health system of HIV treatment, and for every prevention programme, the evidence is pretty muddled,” says Christopher Murray, professor at Harvard’s School of Public Health.

However, studies conducted in recent years point to a third barrier to enhanced Aids support. Many of the most effective methods clash with the values of countries struggling to fight the epidemic and with important funders and influences, such as the White House and the Vatican.

Research suggests the role of condom distribution in cutting infection far outweighs any resulting rise in promiscuity and that free needle-exchange and substitution programmes for hard drug users reduce transmission without creating new addicts. But the US administration emphasises abstinence and loyalty over condom use. Grant recipients must condemn sex workers and refrain from offering abortion advice. Critics say such policies risk undermining organisations best placed to tackle the epidemic, while handing funds to inexperienced religious groups.

Other challenges lie ahead: curbing violence against women, encouraging circumcision and fighting prejudice against high-risk groups such as homosexuals, prostitutes, drug addicts and prisoners.

If they are serious about turning their Aids rhetoric into reality, political leaders will need not only the financial resources to make a difference abroad but also the moral courage to defend controversial policies at home.

Scientists tested to the limit in pursuit of a fiendish target

The world was introduced to the scourge of Aids on June 5 1981, when the Centres for Disease Control in Atlanta issued a short report on a cluster of five unusual pneumonia cases among young homosexual men in Los Angeles, writes Clive Cookson. Within weeks it became clear that many gay men in the US were succumbing to opportunistic infections as their immune defences collapsed.

The cause of this frightening new epidemic – initially dubbed Grid (gay-related immune deficiency) but renamed Aids (acquired immune deficiency syndrome) when it became clear that homosexual men were not the only victims – remained a mystery until French and US scientists identified the virus now known as HIV. Margaret Heckler, the US health secretary, held a dramatic press conference in April 1984 to announce the discovery, adding that a vaccine against HIV would be available for testing in two years.

Today, an effective HIV vaccine remains a distant dream, although the scientific effort to develop one has been greater than any other vaccine research programme in history. The story on antiviral treatments for Aids is somewhat happier: combinations of anti-HIV drugs available since 1996 are estimated to prolong the life of the average patient by 13 years. But most people infected outside the industrialised world do not have access to these expensive medicines.

HIV turned out to be a fiendishly difficult target for vaccine and drug development. It is a “retrovirus”, which uses RNA rather than the usual DNA to encode its genes. This enables HIV to replicate so quickly, with so many genetic variations, that protecting against all the myriad subtypes is a formidable challenge.

The fact that the immune system is HIV’s main target makes fighting it all the harder. The virus employs several biochemical defences against immune attack, such as hiding its surface proteins from antibodies with a cloak of sugar molecules. Once HIV has taken hold in a patient, it inserts itself into the genome of human cells – making it impossible for antiviral drugs to eradicate infection completely, even though they do a good job of keeping symptoms at bay.

According to the United Nations Aids programme, funding for the development of vaccines to prevent HIV infection reached $630m (£339m, €494m) last year – up from $330m in 2000. Much of this comes from public and charitable sources and is channelled through the New York-based International Aids Vaccine Initiative. Seth Berkley, its president, argues that more money is needed to meet “perhaps the toughest public health test of our time”.

When the world is spending $20bn-$30bn a year on Aids, an HIV vaccine would be so cost-effective that expenditure of $1bn a year is justified to develop one, he says: “The problem is that, from the start, Aids has been seen as an emergency – which has given too much short-term and not enough long-term emphasis to Aids research and development.”

There are good scientific reasons to believe that an effective Aids vaccine will eventually emerge. “One is that vaccines can protect monkeys against infection with SIV [the simian version of HIV]. Another is that a few people who are repeatedly exposed to HIV do not become infected, while others manage to hold the infection down with their own immune system without developing Aids,” says Dr Berkley.

There have been more than 70 clinical trials of candidate Aids vaccines and about 30 are still in progress. But almost all are on a small scale. “It is shocking that only one Aids vaccine has gone through a full-scale Phase III clinical trial,” says Dr Berkley. That one, from VaxGen of the US, failed to demonstrate efficacy.

Among the large vaccine manufacturers, Merck of the US and Aventis Pasteur of France are most active in Aids research. Dr Berkley says a Merck vaccine in early-stage trials in the US is “one to watch”.

The human immune system has two arms, one working through antibodies and the other through cells. Almost all the vaccines in clinical trials today are based on cellular immunity. If a dual approach, involving both cellular and antibody-based vaccines, is required to give adequate protection, then another 10 years of development work will probably be needed.

In contrast, the first antiviral drug for Aids, AZT, was approved in 1987. AZT had serious side-effects, the pills had to be taken every four hours and HIV soon evolved resistance to it. But its availability did wonders for patients’ morale. Under pressure from Aids activist groups, drawn originally from the gay community, the pharmaceutical industry accelerated the development of other drugs that worked in different ways to AZT and could be used in combination with it.

“Aids activists in the late 1980s and early 1990s led the way for patient groups in other areas to become involved in clinical trials,” says Nick Partridge, long-serving chief executive of the Terrence Higgins Trust, the leading UK Aids charity. “The activists fought with the drug companies for a while but they soon developed a more collaborative relationship with the industry.”

Since 1996 the benchmark for Aids treatment has been “highly active anti-retroviral therapy” or Haart. This cocktail of three or four medicines is needed because the virus becomes resistant to combinations far more slowly than to individual drugs. “The biggest advance over the past five years has been to lighten the patient’s ‘pill burden’ by combining different drugs in single capsules and developing long-acting versions of them,” says Mr Partridge. “In 1997 it was not uncommon to have to remember to take 20 or 25 pills a day; now the dose might be two pills a day.”

The US Food and Drug Administration has approved 27 HIV products, including new combinations of existing drugs. Most stop the virus replicating by blocking an essential enzyme, though the newest approach is the “entry inhibitor” represented by Roche’s Fuzeon, which stops HIV getting into human cells.

Datamonitor, the business information company, estimates that the total HIV drug market will rise from $6.6bn in 2004 – a figure based on IMS Health sales data – to $12bn in 2015. Morris Paterson, senior Datamonitor healthcare analyst, says only one or two entirely new drugs are likely to enter the market before 2009, though new treatments will be launched at a faster rate after 2010. Products available today will still represent 62 per cent of the HIV market in 2015.

GlaxoSmithKline, which launched the first HIV drug, AZT, still has 38 per cent of the market, with Bristol-Myers Squibb second (22 per cent) and Abbott third (14 per cent). Datamonitor expects all three to have their share cut substantially over the next 10 years, as newcomers and generics enter the market.

According to Dr Paterson, the most promising newcomer is Tibotec, a Belgian pharmaceutical development company bought by Johnson & Johnson of the US in 2002, which has three HIV products in clinical trials. Pfizer could do well with Maraviroc, first of a new category of anti-HIV drugs called CCR5 inhibitors.

Although there is no prospect of a permanent cure for Aids in the foreseeable future, Mr Partridge of the Terrence Higgins Trust believes the drugs industry has done a good job with its HIV research and development. “People who said that Aids activists would drive pharmaceutical R&D away from this field were wrong,” he says. “The reality is that combination therapy is still highly effective for the vast majority of people with HIV.”

THE AGE OF AIDS: FROM OBSCURITY TO EPIDEMIC

■1930/40s: Aids starts in Cameroon, passed from chimpanzees to people. The disease slowly propagates in central Africa, unknown to medical science.

■1959:The earliest known case of HIV infection, identified retrospectively (in 1998) in a long-stored blood sample from the Congo.

■1981: Centres for Disease Control, Atlanta, recognise an unusual cluster of pneumonia cases in gay men.

■1983: Luc Montagnier and colleagues in France discover the virus that causes Aids. This is later identified independently by Robert Gallo in the US and becomes known as HIV.

■1987: Wellcome (now part of GlaxoSmithKline) launches the first anti-HIV drug, AZT.

■1996: New drug combinations, known as highly active anti-retroviral therapy, keep HIV infection under control without unacceptable side-effects.

■2001: First United Nations General Assembly session on Aids produces a big funding commitment from rich countries.

■2005:G8 meeting pledges universal access to Aids drugs in Africa by 2010.