HTB

Dollars, commerce, politics and prejudice all present obstacles to scaling up access to treatment in resource poor countries

Graham McKerrow, HIV i-Base

The question of how to scale up access to treatments in poor countries dominated the XV International AIDS Conference in Bangkok and it quickly became clear that different regions, different countries and different organisations would be pursuing their own ways of trying to treat as many people as possible.

There is no one-size-fits-all solution to this enormous task because funding sources, local conditions, infrastructure, culture and needs all vary widely. What suits a middle-income democracy with a free-at-the-point-of-delivery public health service, like Brazil, would not suit a poor but stable country like Uganda, or a country like Cambodia, with political conflict and widespread corruption which make greater government involvement as undesirable as it would be ineffective.

Much of the focus of the conference was on the sharing of experiences of how poorer countries were already treating people. Many of the delegates I spoke to from developing countries were attending their first International AIDS Conference and reported that the information was invaluable. In contrast, delegates from rich nations, many of whom had been to previous conferences, said they found little of value to take home. This was in part because the plenary sessions that in the past have been used to give state of the art overviews of scientific and clinical information were replaced with single-country and single-project reports from the developing world. They didn’t tell other countries how to scale up treatment provision but shared experiences so that individual governments, non-governmental organisations (NGOs) and projects could draw on a variety of experiences around the world.

Treatment activists and others criticised the American $15 billion President’s Emergency Plan for HIV/AIDS Relief (PEPFAR) for being limited to just 15 countries regardless of need elsewhere, and for promoting a conservative morals agenda by emphasising abstinence and faithfulness before condom use in the so-called ABC policy (Abstinence, Be faithful, and “when appropriate” use Condoms). President George Bush has called this a “moral message” and has emphasised the primary importance of abstinence in his policy. Critics at the conference pointed out that abstinence was not an option for many women, some said most women, in the poorest regions. The conference heard particular criticism of the promotion of faithfulness as a prevention method because sexual fidelity to a partner who is positive or becomes positive offers no protection from the virus. Similarly, marriage can put a woman at risk in some regions marriage itself is a high risk factor for contracting HIV. President Bush has said PEPFAR will prioritise funding for faith-based groups. The 15 nations picked by the US are Botswana, Côte d’Ivoire, Ethiopia, Guyana, Haiti, Kenya, Mozambique, Namibia, Nigeria, Rwanda, South Africa, Tanzania, Uganda, Vietnam, and Zambia.

By comparison to PEPFAR, the Global Fund to Fight AIDS, TB and Malaria appeared to be the funding body that could do no wrong, and Fund The Fund, a loose group of activists from several rich nations, made their support clear throughout the week. However, several speakers from countries that have received money from PEPFAR expressed their thanks for the American money, and such gratitude is likely to grow as more of the $15 billion gets through to projects in the chosen countries. The US Global AIDS Coordinator, Randall Tobias, cancelled a speech and a press conference but did finally address the delegates although he made no new announcements. Tobias was dogged by mainly American protesters everywhere he went at the conference. When he did speak it was after a noisy protest and activists continued to hold up placards reading “He’s lying”.

The United States was widely criticised for limiting PEPFAR money to brand name drugs and for supporting the system of patent protection that prevents wider production and distribution of generic drugs.

Only a small audience attended Tobias’s lecture in the main conference auditorium and the demonstrators stood up in front of the stage and broke into cries of “lie, lie” when Tobias played with statistics to claim: “America is the world’s largest contributor to the [Global] Fund – making 36% of all pledges to date.” This overlooked the fact that the US has slashed its support for the Global Fund from $546m this year to a promise of just $200m a year from next year, which is only slightly more than the $180m promised by France. The independent watchdog Aidspan says the US pledge represents just 18% of its equitable contribution according to the wealth of the nation.

Tobias also misled his audience when he claimed PEPFAR would fund the use of the cheapest, safest drugs regardless of who produced them: “These drugs may include brand name products, generics or copies of brand name products.” In fact, the United States refuses to recognise the World Health Organisation system of approving (“prequalifying”) safe generic drugs and has introduced new bureaucracy that will exclude most generic drugs in favour of more expensive brand name medicines. Critics point out that Tobias is a former Chief Executive Officer of Eli Lilly. In what seemed to be a reference to these new regulations, Tobias said: “America will not have one health standard for her own citizens and a lower standard of “good enough” for those suffering elsewhere. However, if the money is reserved for more expensive brand name drugs this can only result in fewer people being treated than could otherwise be the case.

America’s “AIDS Ambassador” told the conference that PEPFAR would prioritise working with “indigenous organisations” that have the trust of local people. And he indicated his intention to prioritise faith-based organisations by adding: “The fact is that among those indigenous organisations, the Buddhist temples and monasteries, the churches, the mosques and the synagogues are among those who have gone where no one else would go.”

The demonstrations that punctuated Tobias’s lecture prompted both applause and boos from the audience. As he left the auditorium, the demonstrators stood and chanted “Shame. Shame”.

Tobias ducked out of a scheduled presentation on the first day of the conference and his place was taken by Dr Mark Dybul, the Deputy Chief Medical Officer in Tobias’s office, who made a very strong case for PEPFAR by quoting statistics about how much has been achieved with PEPFAR dollars. He, too, was greeted with cheers and boos from the audience. An activist from ACT-UP New York and Health GAP spoke at the delegates’ microphone to criticise the US government for using the conference as a “PR platform”. The speaker asked: “Why is the US government undermining generic drugs? Why has the US government reneged on Doha [the World Trade Organisation agreement that, among other things, allowed greater production of generic drugs]? Why has the US government drastically underfunded the Global Fund?”

Gregg Gonsalves, Director of Treatment and Prevention Advocacy at Gay Men’s Health Crisis, New York, told the same session: “It has been the AIDS community that has been at the front of all progress in the field of AIDS … Professionals are still loath to see PWAs in positions of control; they would rather see us as patients, victims, carriers.” Dybul said the answer was to protest in countries around the world to “mobilise PWAs and bring the community to the table.” Sharonann Lynch from ACT-UP New York and Health GAP, said the key was to make the Country Co-ordinating Mechanisms (CCMs, committees that coordinate each country’s grant applications to the Global Fund) involve PWAs, and to ensure that bilateral donors such as the United States through PEPFAR, use the CCMs.

Also on the first day of the conference, Médecins Sans Frontières (MSF) held a packed three and half hour session on Access to Affordable ARVs: Patents, Prices and Quality. Fernando Pascual, a pharmacist with MSF, said medicines for first line therapy cost 1.5 times more in developed countries than they do in developing countries. Second line drugs cost 26 times more because there is very little generic competition for new second line treatments. The so-called originator companies, those that invent and develop a drug, only cut the prices of their first line therapies after other companies have produced generic versions. Allowing generic competition is a key issue, said Pascual. A UNICEF worker from China emphasised that the key issue was generic production of second line drugs and asked what influence the Clinton Foundation, headed by the former US President Bill Clinton, was having. Pascual responded that Clinton was negotiating prices at country level, which would reduce prices in Rwanda and soon in Mozambique. A representative of the Nigerian Ministry of Health said that PEPFAR had assured Nigeria that they would be funded for buying generic drugs. Rachel Cohen, the US Director of MSF’s campaign for Access to Essential Medicines, responded: “We have to be sceptical of assurances like that from the US government because they have said they will only fund drugs approved by the US government. In our experience, they will have to procure brand name medicines because of PEPFAR regulations. The prices mean that they could treat three times as many people if they were allowed to buy generics.”

Pascale Boulet, of the MSF Campaign for Access to Essential Medicines, was keen to nail the myth that companies can hold international patents: patents are granted by National Patent Offices for each country to reward invention and facilitate the disclosure of the invention as a sharing of knowledge. A patent provides the holder with a monopoly in the country where it is granted and the World Trade Organisation (WTO) TRIPS (trade-related aspects of intellectual property rights) agreement ties signatories to making the monopoly last for a minimum of 20 years. One hundred and forty countries signed the TRIPS agreement.

Countries such as Brazil, Thailand and India did not grant patents before the TRIPS agreement so they have generic production of older, first line therapies, but TRIPS means that new drugs are likely to be patented which means that as more people are treated, and as virus develops resistance to the drugs, the world will become more dependent on brand name drugs and producers of generics will be squeezed out of the market.

It should be remembered that the issue of patents can sometimes be a red herring because many of the biggest companies do not file patents in Africa. Equally, it is worth pointing out that manufacturers of generic drugs are not necessarily angels; The Mumbai, India-based company, Cipla, has patented Triomune (lamivudine, stavudine and nevirapine) in South Africa and is seeking patents on the product in 17 other African countries. Treatment activists have expressed outrage.

The good news is that the Doha declaration – a WTO agreement signed in Doha, Qatar – allows signatory countries to issue compulsory licences to protect public health and to “promote access to medicines for all”. Thirty-two of the WTO’s poorest member countries are classified as Least Developed Countries (LDCs) and they do not have to grant or respect patents on medicines until 2016. MSF is urging the countries to take full advantage of this clause in the next 12 years and to work to have it extended after the 2016 deadline.

Boulet explained to delegates how the national authority responsible for patents could issue authorisation to manufacture or import generics without permission of the owner of the patent. Examples of past uses include the UK Ministry of Health buying generic tetracycline from Italy in 1965, and more recently the Indian government importing Kaletra from Thailand.

Boulet highlighted the main concern for the future as being how to ensure sources of affordable medicines and how to tackle the cost of widely patented second line treatments. The main concern for the immediate future was the development of bilateral “free trade” agreements usually between the US and poor nations that threaten existing trade flexibilities by persuading countries to give up their rights to use generic medicines. Cohen cited the example of Uganda, which has been under sustained pressure from the US for several years to amend legislation to introduce respect for patents, even though as an LDC they don’t have to.

Cohen and Pascual talked about how the United States government has rejected the WHO prequalification scheme that approves generic drugs as safe and effective. Instead, the US has published a draft document outlining regulations to approve drugs to qualify for PEPFAR funding. MSF has joined other observers in saying the regulations will make it easier for brand name drugs to get approval from the US authorities and difficult, slow and expensive for generic manufacturers to do the same for their products. Pascual commented: “The WHO prequalification is perfectly good and we don’t need to duplicate approval in this way.”

Dr Selina Lo, MSF’s Medical Coordinator in China, spoke about their project in Nanning City where they have 100 people on ARVs. She said the only fixed dose combinations (FDCs) or combined pills available to them were Combivir and Trizivir but the MSF doctors wanted to be able to use FDCs containing combinations of other drugs. She said they didn’t have access to any second line drugs. Kaletra is registered but not marketed. They want other combinations using 3TC, besides Combivir and Trizivir, and although GlaxoSmithKline has decided to preferentially price 3TC, that doesn’t help provide FDCs for patients – “which is something we will continue to push for,” said Lo. She pointed out the complexity of the problem involving patents when she said that 3TC has 51 patents on it in China alone.

A speaker from Egypt said that because that country officially had a low HIV prevalence most brand name drugs were not marketed there. Pascual said this was a common problem in countries with low prevalence and there was nothing they could do to make private companies market their drugs. He said the best thing to do was to press governments to issue compulsory licences, which allow the production and distribution of generic versions of patented brand name drugs.

Cohen said there was a problem procuring drugs at reasonable prices for middle income countries where lower prices, also known as differential pricing, announced by the major pharmaceutical companies, were often “virtual rather than real”. Zahedal Islam, head of the MSF mission in Ukraine, said they had 1,000 mothers and children in their programme, and there were no patent barriers in the country which meant that generics (AZT, 3TC and nevirapine) were allowed there. However, because the drugs are not marketed in the country they have to be imported by MSF and shipping and customs costs take the cost of drugs up to the non-discounted rich nation price.

On the Tuesday morning of the conference, a demonstration by the Thai Positive People’s Group demanding an end to the system of patents, greeted the start of a session in the main conference auditorium that asked: “Are Intellectual Property Rights a Barrier to Increased Access to ARVs?” In an appearance that surprised many observers, Hank McKinnell, Chairman and Chief Executive Officer of Pfizer, put the case for patents. He said intellectual property (IP) rights were what allowed companies like his to make enough money to sustain investment in technology. IP drives new research, which creates new treatments, which will help patients in the future, he argued. “We have to ask ourselves what is the balance of treating patients today and in the future.” He said Pfizer would work with “any government anywhere” to give people access to Pfizer medicines, “but we will not negotiate with people whose purpose it is to appropriate our knowledge for sale by others at a profit.”

Walden Bello, Professor of Sociology and Public Administration at the University of the Philippines, undermined McKinnell’s main argument by pointing out that governments, universities and public bodies spend three times as much on research as do the pharmaceutical companies. He said that in the past big pharmaceutical companies – ‘Big Pharma’ in the jargon – doesn’t develop new drugs, it buys them from smaller companies and other sources in order to market them. They spend more on marketing than on R&D. He called on TRIPS to distinguish between life saving medicines and drugs like Viagra “and other toys” which Pfizer should continue to be allowed to market as they do.

Bello said branded medicines retail at 20 to 100 times their manufacturing costs, that the pharmaceutical industry is the most profitable industry in the United States and he listed what the companies’ CEOs were paid and – getting personal – he said McKinnell was highest paid of all on $28m annual pay plus $30m stock options. McKinnell told delegates these figures were inflated but he did not reveal what he was paid.

When discussion was opened to the floor, a French economics professor called for an independent task force to establish industry R&D costs.

Jonathan Berger of the Treatment Action Campaign and the AIDS Law Project at the University of Witwatersrand, South Africa, said it was necessary to amend the TRIPS agreement and to create incentives to develop new drugs while changing how patents were used. Countries should exploit the public health safeguards and flexibilities in the TRIPS agreement and the agreement needed amending so that a single compulsory licence would be enough to ensure production and distribution of generic drugs. He called on countries with manufacturing capabilities to lead the way but added that those without manufacturing capabilities should also have access to generics. The obstacles to scaling up access to treatment were that countries were failing to implement the Doha exemptions to their full extent, and bilateral and regional Free Trade Agreements (FTAs) were being negotiated “all round the world” that limit the possibilities for generic production and distribution. These retrograde bilateral and regional agreements are attracting little public attention, are often highly technical in nature, and are being negotiated in secret. They already affect the nations of the North American Free Trade Association, Caribbean Free Trade Association and the Southern Africa Customs Union, as well as Chile, Jordan, Morocco, Singapore and Australia.

A speaker from an NGO in India said that scaling up access to treatments was a lot more complicated than simply sidestepping patents because India had several thousand pharmaceutical companies including manufacturers of generic ARVs, but only 12,000 people, 1% of those who need treatment, were receiving ART. In countries like India where the basic delivery mechanism for any kind of drug is very weak, producing generics is only the first step towards treating people. Several speakers in other sessions also made the point that, India has 5.1 million people with HIV/AIDS, the largest number of any country other than South Africa, but despite the advantage of a developed domestic generics industry, the Indian government has failed to treat people. The appearance of Sonia Gandhi, head of the country’s Congress party, on the last morning of the conference, suggests that the new government may take the problem more seriously than its predecessor. She acknowledged that “we need to do a great deal more” and added: “I would like to take this opportunity to categorically assert the determination and ability of the government and the people of India to meet this daunting challenge just as effectively as it did in the campaign to eradicate smallpox some decades ago.”

There was considerable debate at the conference about how to decide who gets treatment in circumstances where need overwhelms supply. Laura McGough, an historian from Johns Hopkins University in the US, said there were already several rationing methods that controlled who got treatment; she said PEPFAR rations treatment to just 15 countries, the Global Fund rations by programme proposal, in some countries treatment is rationed to state employees, it is rationed by stigma or rationed to people with fixed addresses and family support. She and colleagues evaluated resource allocation decisions taken following four medical discoveries between 1922 and the present day. She told delegates that their recommendations were 1) to encourage public participation in establishing rationing criteria, 2) not to use social criteria as ‘proxy’ for adherence criteria, and 3) to act constitutionally. She concluded: “Each country needs to engage these questions and come to their own conclusions about inclusion criteria.” [1]

Miriam Rabkin of Columbia University, New York, reported on the non-medical eligibility criteria used by different projects in the Columbia MTCT-Plus programme. This initiative provides care and support to women, children, and their family members at 12 MTCT-Plus sites in 8 countries. She said that first there were programmatic criteria that limited resources to women, children, partners and household members, then there were clinical/biological criteria to decide who would be treated and finally it was devolved to each site to decide how to define “households” and other criteria, using community boards to reach decisions. She reported to delegates that no one criterion was used by all sites; some demanded recipients be “within the neighbourhood”, one insisted on a commitment to safer sex, one insisted on a fixed address, and one demanded participants be single or in monogamous relationships (although after discussion this requirement was dropped). Many criteria were abandoned within the first six months. Rabkin said: “Sites are at the ethical forefront of deciding on access criteria and community involvement is essential.” [2]

There was also discussion about the best use of resources to identify and prioritise people who need treatment. Harmony Fusco of the Centre for Infectious Disease Research in Zambia – where fewer than 5,000 patients are on ARVs and the government target is to have 100,000 on treatment by the end of next year – said that to enrol one patient on ART they had to be willing to be tested, willing to undergo clinical and lab investigation and willing and ready to start treatment. She said they found they had to pre-test counsel 72 antenatal patients to enrol one on ART, but they had to pre-test counsel only 3 TB patients to enrol one on ART. “This dramatically cuts enrolment costs,” she said, adding: “It is estimated that 80% to 90% of hospital in-patients are HIV-positive so there are high-yield – if you like to use that phrase – patient populations.” [3]

The scale of the problem of identifying people suitable for treatment was illustrated by Chris Archibald of the Centre for Infectious Disease Prevention and Control, Canada, who said his research showed there are about 32 to 34 million undiagnosed people with HIV. The success of the worldwide battle to combat HIV will rely on population coverage, not just treating people who present “and that requires steps to tackle stigma and prejudice”. This also has implications for prevention because knowing one’s status is the gateway to both prevention and care, he said. [4]

Among dozens of reports from individual projects in poor countries around the world, Frencesca Galletti of the WHO reported on the problem of individual healthcare projects having to care for people over large geographical areas and how this makes it difficult for people to consult their doctors about side effects and illness, to ensure they receive proper monitoring. She reported that in Uganda they are distributing blocked mobile phones that can only ring three numbers of healthcare workers so people can have long-distance consultations.

In a lunch break conversation, Peanh Sinal, Director of the Minority Organisation Development Economy in Kampong Thom, a province of northern Cambodia, described his work with racial minorities, mainly the Kouy people. MSF and other NGOs are treating about 7,500 people with ARVs in Cambodia and about another 20,000 people urgently need ART. Sinal was clear that the main problem in his country was government inaction due to political infighting and corruption, and he said the solution was for the Global Fund to finance the NGOs to increase the number of people being treated.

While MSF tackled the lack of generic versions of second line therapy, there needs to be emphasis on the dangers of treating people with multiple complications with only first line therapy. There will be treatment failure, people will get ill and die, and this could lead to demoralisation of patients and carers. We risk repeating the errors of the AZT monotherapy experience in the West a decade ago when information about treatment failure was kept from people for fear that it would take away hope; but leaving people with false hopes based on unrealistic expectations can only lead to disenchantment and future mistrust of treatment, healthcare workers and information providers. It is important that current FDC and MTCT programmes include information about adherence, resistance and side effects.

In one of the few presentations on human rights – a key part of so many aspects of the battle against HIV – Ronald Labwayii of Livelihood International in Kampala, Uganda, presented research that showed that there is a hidden epidemic throughout Africa among people who have homosexual sex. The research reveals huge levels of official and unofficial discrimination and violence against men who have sex with men (MSM) and women who have sex with women (WSW) throughout the continent with the exception of South Africa. They found high levels of rape in police stations, violence in correctional institutions, and sexual abuse of boys and girls. They also found that in Senegal, for example, the mean age of first sexual experience was 15 and one third of the sample said their first sexual partner was a member of the family. Condom use in all circumstances was very low. He concluded: “AIDS is fuelled by violence against MSM, and prejudice against MSM,” and yet in most of Africa there are no education, prevention or care projects appealing to sexual minorities. A delegate speaking from the floor said the same problems affected MSM in eastern Europe.

If Africa made its presence felt four years ago at the Durban conference, this year at Bangkok it was noticeable that there were many more delegates from neighbouring Asian countries including China, as well as from central Asia, Eastern Europe and the Russian Federation. This reflects the growing concern about HIV in these countries and also demonstrates the importance of alternating the International AIDS Conference between developed and developing countries. Finally, there was a graffiti wall in Bangkok and among the jokes and anger, one anonymous delegate had written: “Where is the Middle East and North Africa in the fight against HIV/AIDS?” and very small writing in a different hand next to it had added: “I live there. AIDS crisis coming soon.”

References:

  1. McGough LJ, Reynolds SJ, Quinn TC et al. Which patients first? Setting priorities for antiretroviral therapy where resources are limited. XV Intl AIDS Conference, Bangkok. Abstract WeOrB1277.
    http://www.iasociety.org/Default.aspx?pageId=11&abstractId=2171277
  2. Rabkin M, Tonwe-Gold B and El-Sadr W – Non-medical eligibility criteria for pilot HIV/AIDS treatment programmes in resource-poor settings: The Columbia University MTCT-Plus experience. XV Intl AIDS Conference, Bangkok. Abstract WeOrB1278.
    http://www.iasociety.org/Default.aspx?pageId=11&abstractId=2173489
  3. Fusco H, Chi B, Sinkala M et al. Cost and enrolment implications of different target populations in the rapid scale-up of antiretroviral treatment programmes. XV Intl AIDS Conference, Bangkok. Abstract WeOrB1281.
    http://www.iasociety.org/Default.aspx?pageId=11&abstractId=2173922
  4. Archibald CP, Alexander P, Gatali M et al. Undiagnosed HIV infections: The rate-limiting step for the 3 by 5 Initiative? XV Intl AIDS Conference, Bangkok. Abstract WeOrB1282.
    http://www.iasociety.org/Default.aspx?pageId=11&abstractId=2175838

Links:

Professor Walden Bello
http://www.zmag.org/bios/homepage.cfm?authorID=113

Jonathan Berger
http://www.alp.org.za/view.php?file=/about/bios/20020627_bergerj.xml

MSF
http://www.accessmed-msf.org/index.asp

Randall Tobias
http://www.state.gov/s/gac/rl/rm/2004/34366.htm

Gay Men’s Health Crisis
http://www.gmhc.org/

Pfizer
http://www.pfizer.com/main.html

Links to other websites are current at date of posting but not maintained.