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International Association of Physicians in AIDS Care, January 2000 Journal
Rebecca Voelker
For most in the audience, it was a sight rarely seen at an international AIDS conference. Seated side by side on the dais were representatives from some of the world's major pharmaceutical companies: Glaxo Wellcome, Merck, DuPont Pharmaceuticals, Abbott Laboratories, and Bristol-Myers Squibb.
Not only had they joined the same panel discussion, the topic was not one traditionally associated with the pharmaceutical industry: thinking "outside the box" on ways to improve access to drugs, medical education, and information technologies for people living with HIV and AIDS in the world's poorest countries.
But even as drug company representatives noted their own firms' accomplishments in developing antiretroviral drugs, collecting efficacy data, and ensuring consistent drug supplies, a single, non-scientific term emerged in their talks of advancing treatment--partnership.
Partnership was the operative word at an international conference on healthcare resource allocation sponsored by the International Association of Physicians in AIDS Care (IAPAC). Throughout the Third International Conference on Healthcare Resource Allocation for HIV/AIDS and Other Life-Threatening Illnesses held in Vienna, Austria, October 11-13, 1999, formal panel discussions and informal hallway conversations focused on the need for partnerships, and the undeniable fact that HIV will not be vanquished without the participation of diverse stakeholders in the pandemic.
"We're going to find a solution together," Randy Tressler, MD, of Abbott Laboratories told the 250-plus physicians, drug industry representatives, economists, and activists from some 35 countries who attended the conference. "The part we need to be aware of is that we not stop to fight with one another, but that we look at how we can meet the needs of each of the groups" that are battling the virus.
This third installment of IAPAC's resource allocation conference also pointed squarely at the need for global cooperation, as worldwide gaps between wealthy and poor grow wider.
"While the richest 20 percent of the world's population controls 82.7 percent of global income, the poorest 20 percent has to live with 1.4 percent [of global income]," said Joseph Saba, MD, conference chair and clinical research specialist with the Joint United Nations Programme on HIV/AIDS (UNAIDS). "Developing countries are left with a sad combination of low income and high HIV prevalence. Unless there is some kind of transfer of resources from the North to the South, there is no way we will be able to control this epidemic."
During opening remarks videotaped for the conference, Archbishop Desmond Tutu said industrialized countries have "a moral obligation" to assist resource-poor regions of the world. "We are members of one family," Tutu told conference delegates.
Conference Secretary and IAPAC Executive Director José Zuniga reminded conference delegates that nearly 1.3 billion people worldwide live on less than $1 a day, the World Bank designation of extreme poverty. "Such absolute human deprivation as we are witnessing today explains why upwards of 200 million children under age 5 suffer from malnutrition and anemia, and why 55 percent of the poorest segment of the world's population dies of communicable diseases, compared with 5 percent of the highest income group."
Without better use of resources and reshuffling the deck of global priorities, Zuniga said the "three-headed plague" of poverty, disease, and human isolation threatens to destroy entire populations.
Sidestepping US anti-trust regulations that prohibit them from discussing specifics on pricing and other corporate strategies, pharmaceutical company representatives described partnerships they have embarked on in developing nations and suggested new collaborations they hope could strengthen existing efforts.
As for thinking outside the box, James Sapirstein, RPh, of Bristol-Myers Squibb, said an idea from IAPAC's resource allocation conference held last year in Cancún, Mexico, is taking shape in five southern African countries--Botswana, Lesotho, Namibia, South Africa, and Swaziland. Secure the Future, which was formally launched in May 1999, represents a pledge from Bristol-Myers Squibb of $100 million over five years to fund medical research aimed at helping women and children with HIV/AIDS; assisting community-based organizations (CBOs) and non-governmental organizations (NGOs) in providing services, including home-based care and care for orphans; and expanding capacity-building education programs. [Editor's Note: IAPAC serves as the official monitor of the Secure the Future initiative.]
"Who would have thought a [pharmaceutical] company would have contributed that amount of money to this kind of cause?" Sapirstein said. "It was unprecedented, but we moved it forward in a matter of months."
During the Vienna conference, Bristol-Myers Squibb committed additional resources to IAPAC's God Bless the Child initiative, which asks religious congregations to pledge funds for triple combination therapy for children in resource-poor nations. Soon to be operational in Romania, additional funding is needed to expand the program to South Africa.
IAPAC Board of Trustees Chair Allen Freehling, PhD, of University Synagogue in Los Angeles, announced at the Vienna conference that his congregation has pledged funds for the program, and he challenged pharmaceutical companies to donate antiretroviral drugs. With a handshake before hundreds of conference delegates, Mark Ahn, PhD, of Bristol-Myers Squibb accepted the challenge. Ahn said his company looks forward to building relationships with faith communities and that, after more than 100 years of doing business in South Africa, "we know how to get drugs to the people."
In developing partnerships, pharmaceutical companies have taken notice of key concepts that UNAIDS has established in its drug access initiative implemented over the past two years in Chile, Côte d'Ivoire, Uganda, and Vietnam. "Experience shows that access to AIDS drugs can best be met when government enters into partnerships with other sectors," said Merck's Jeffrey Sturchio, MD. Another key, Sturchio noted, is that "sustainable solutions are the ones developed by local experts."
Toward that end, the Merck Company Foundation has joined with the Harvard AIDS Institute and the François-Xavier Bagnoud Center for Health and Human Rights at the Harvard School of Public Health to create the Enhancing Care Initiative (ECI). The initiative has launched programs in Brazil, Senegal, South Africa, and Thailand in which teams of local experts from medicine, government, NGOs, CBOs, and other arenas are formed to identify problems and solutions in HIV/AIDS care in their own regions. For example, program leaders in Brazil prioritized access to care for women, while those in Thailand are focusing on home-based care.
With coordination from experts at Harvard, Sturchio said, "We hope ECI will help customize concrete, practical improvements that will advance the quality, delivery, and outcomes of care for men, women, and children living with HIV/AIDS in the developing world."
Headline-grabbing protests have diminished in recent years, but drug makers still are mindful of criticism that their prices impede access to care. To counter their critics, drug industry representatives portray the big picture, pointing to the cost of the healthcare infrastructure needed to deliver HIV/AIDS care. Drug prices, they say, are just one component.
"Is the solution to lower the price of drugs, or to find another way around [the cost of the infrastructure]?" Abbott's Tressler asked conference delegates. Anticipating criticism, but not getting any from activists in the audience, Tressler said drug prices are not necessarily driving the cost of HIV care. "Three times the cost of the drug is how much it costs for the infrastructure to deliver that drug," he asserted.
To cut infrastructure costs, Tressler encouraged governments and private sector industries to join forces to negotiate prices for bundled services and products-testing kits, monitoring equipment, and drugs. He noted that in some developing nations, ministries of health and major industries such as mining and insurance are buying the same products and services independently of each other. "It would be more efficient for them to work together," he noted.
The Pan American Health Organization (PAHO) has used that concept to build a successful immunization program in member countries, where vaccination coverage has reached from 85 percent to 90 percent. A key mechanism of the program's success has been bulk vaccine purchasing negotiated by PAHO and financed through a revolving fund established by the member states, said Rafael Mazín, MD, PAHO's regional adviser on HIV/AIDS issues. According to Mazín, PAHO now is looking at ways to duplicate that success in the purchase of antiretroviral drugs.
"It's an idea that is just taking off," he told conference delegates. PAHO member states recently embarked on setting up a new revolving fund to buy drugs for the treatment of malaria, tuberculosis, leishmaniasis, and insecticides for vector control. After analyzing data on combination antiretroviral therapy and considering the Harvard ECI program's potential to advance treatment in Brazil, Mazín said antiretroviral drugs and reagents to monitor antiretroviral therapy were included in the new fund.
Each member in the fund will pay a fee that goes into a capitalization account and a 3 percent surcharge on the amount of drugs purchased to set up a reserve account. Mazín said reserves of at least $500,000 will be maintained, and PAHO will invest 0.5 percent of the reserves in primary prevention programs in member countries.
"We included ARV therapy as a way to invite member states to incorporate into their guidelines for the management of people living with HIV and AIDS the use of these pharmaceutical products," said Mazín.
In essence, PAHO is creating a new market, which should be good news for people with HIV/AIDS, and for pharmaceutical manufacturers. But the potential for new markets in developing nations raises a host of issues around globalization, patent rights, and trade agreements.
Globalization--the free movement of goods and services across national borders throughout the world--has engendered hopes and fears, said Frans Stobbelaar, a World Health Organization (WHO) economist. "If all goes as we want it, economic development will improve the health status of many people around the world, [as] information and communication will improve knowledge about health and healthcare. Technological change will make unaffordable treatments affordable," he said.
Yet some fear that globalization will threaten health status in some regions of the world, Stobbelaar noted. "There is concern that unequal access to the gains of globalization will increase inequalities in the world, not only between the developed and developing worlds, but within countries."
In terms of bringing antiretroviral drugs and other therapies to poor countries, particularly in the ravaged nations of Africa, debates over patent protection and trade laws have struck a shrill chord. A main point of the debate is interpretation of provisions on compulsory licensing and parallel imports contained in the 5-year-old Trade-Related Intellectual Property Rights (TRIPS) agreement of the World Trade Organization (WTO).
The issue boiled over last summer in demonstrations targeting US Vice President Al Gore, who is co-chair of a US/South Africa Binational Commission charged with handling trade and aid matters. Gore was accused of threatening South Africa, which UNAIDS estimates to have a 13 percent HIV/AIDS prevalence rate, with trade sanctions if the South African government tried to expand access to AIDS drugs through compulsory licensing and parallel imports. The Clinton administration argued that the TRIPS Agreement does not permit the use of these two mechanisms.
Compulsory licensing allows countries, for a variety of reasons that include national emergencies and drug shortages, to direct a patent holder to license the use of its patent to a third party. Parallel imports allow a country to purchase products in regions where they are sold at lower prices, and then re-sell them at home at the lower price without authorization.
During a conference panel that explored the TRIPS Agreement and the effect of patent protection on drug access in developing nations, Thailand's minister of commerce, H.E. Supachai Panichpakdi, gave a methodical analysis of the agreement.
While it gives exclusive rights for the production, use, sale, and importation of products to patent holders, Panichpakdi (who will be the next director of the WTO) said the TRIPS agreement also contains provisions that recognize the needs of poor countries.
For example, Article 8 of the agreement states that WTO members may adopt appropriate measures to protect public health, nutrition, and socioeconomic and technological development. The same article states that appropriate measures may be used to prevent the abuse of intellectual property rights or restraint of trade.
Further, he explained that Article 31 of the agreement allows use of a patent without the holder's permission under strict conditions in extreme emergencies, or in cases of anti-competition practices. "The TRIPS Agreement offers a reasonable approach in balancing the exclusive economic rights of the [patent] holder and the rights of the public at large," the commerce minister told an attentive audience.
Harvey Bale, PhD, of the International Federation of Pharmaceutical Manufacturers Associations, said the TRIPS Agreement's patent protections will provide an incentive for developing nations that have the infrastructure to begin their own research and development programs. He cited the case of a company in India that recently developed and licensed a new, once-a-day formulation of the antibiotic ciprofloxacin.
"These companies now are doing research," Bale said. "To weaken TRIPS would send them back to what they were doing in the past, and that is not good for public health."
Bale also noted that the TRIPS Agreement requires governments to stamp out counterfeiting, which he called a "public health scourge" in many developing nations. "Many products in Africa and Latin America do not work; they're not genuine products," he said.
He also downplayed the importance of compulsory licensing as a mechanism to increase access to treatment. "Compulsory licensing is not a consumer benefit, it is an industrial benefit to help the companies," which still may receive royalties on their products. In some instances, he added, pharmaceutical companies have offered larger discounts on their patented products than the price reductions yielded through compulsory licensing.
Even so, health policy consultant Ellen ‘t Hoen said that extended patent protection may result in price increases that could keep some critically important drugs, such as tuberculosis medications, off of the WHO's essential drug list and render them unavailable in developing countries. The TRIPS Agreement currently provides for a minimum 20 years of protection for new medications. She noted that that is why parallel imports and compulsory licensing are so important, suggesting that an essential medications research agenda should be set. Drugs that are good candidates for compulsory licensing schemes in developing countries should be identified so they can be developed as public health tools, she said.
She also expressed concern, because the TRIPS Agreement is being implemented in different ways in different countries, that industrialized nations where large pharmaceutical companies are based will pressure developing countries to make concessions that are not specifically stipulated in the agreement. Developing nations that do not have the appropriate legislative mechanisms have until 2005 and 2006 to develop those laws and implement the TRIPS Agreement. "Good patent legislation has a balance; it protects the patent holder and the people who need the product," ‘t Hoen said.
But Richard Wilder of the World Intellectual Property Organization pointed out that pharmaceutical companies still would be required to do the legwork involved in obtaining patent protection. "One cannot obtain an international patent; if you want patent protection, you have to go to each and every country, or in some cases regions, in which you want patent protection," he said.
Pharmaceutical companies generally apply for patent protection in about 60 countries when a new product is introduced, Wilder said, noting that his organization has 171 member countries. "My understanding is that few, if any, [companies] apply in sub-Saharan Africa, with the possible exception of South Africa, for patents," he said.
Adrian Otten of the WTO said the TRIPS Agreement does attempt to find balance between the interests of patent holders and product users. Despite concerns that patent holder rights will prevail, he described a "macro way" in which users' rights are upheld in the agreement.
"There is the possibility for generic producers to use the patented product without authorization before a patent expires so they can get regulatory approval from public health authorities to get the product on the market as soon as the patent expires," he said. Otten also noted that patent holders have to disclose the details of their invention to obtain protection in the first place. And, he said, conditions for compulsory licensing might be relaxed in areas where anti-competitive practices occur.
Despite the "macro" view, said Otten, "I don't pretend that all of our members think this balance is ideal."
In the meantime, pharmaceutical companies appear to be increasing their efforts to join all stakeholders in solving the considerable funding challenges of HIV/AIDS. "We believe that resolving the issue of HIV is an economic issue," said Sapirstein of Bristol-Myers Squibb. "We have proposed a closed meeting, with all constituents being at the table—not just government, not just the pharmaceutical industry, but also members of the private sector."
The effort is known as Uniting for a Solution, and Sapirstein said the objective of such a meeting is the development of an HIV/AIDS public benefit program that can be adapted for numerous countries of the developing world. In Africa, he noted, private sector companies in the mining, oil, natural resources, insurance, and tourism industries are important partners in developing a model program.
"Our goal with this type of meeting is to have everyone put their cards on the table and come up with the proper cost-benefit analysis to figure out exactly what is the price tag of the solution," he explained. "Once we know the price tag, we can figure out how to fund it; it's a complex subject."
But that scenario still may be years in the future. At the present time, said Ugandan physician Peter Mugyenyi, MD, "We look ridiculous when we tell patients that drugs are available and then we tell them the cost." Even at discounts of up to 75 percent, he said, antiretroviral drugs are unaffordable in most developing countries on the African continent.
Synthesizing one of the most critical messages of IAPAC's conference, Mugyenyi said all developing countries of the world must unite to harness their buying power. "There must be a mechanism to turn us into a buying power to get drugs at an affordable cost."
As a century of remarkable achievement offset by growing inequalities came to a close, Lieve Fransen, MD, PhD, introduced a new world theory that is beginning to take root in the minds of international health and development experts.
The theory goes something like this: As globalization makes the world a smaller place, both the public and private sectors are willing to make investments that benefit the very poorest of countries and those that are further along in their development schemes. Within this framework, health status is becoming a more important part of reducing poverty because the definition of poverty itself is changing.
"We're moving away from income-spending definitions of poverty to [new ones] based on the capacity of the poorest to improve their own condition. So health status becomes as important as income," Fransen, coordinator of the European Union's HIV/AIDS program in developing nations, told delegates at IAPAC's Third International Conference on Healthcare Resource Allocation for HIV/AIDS and Other Life-Threatening Illnesses.
"This New World theory of human and social development thinking suggests that better distribution of health outcomes as well as income is equally instrumental in achieving higher economic growth and higher social capital," she explained. In some quarters, she added, public policy that improves health status and increases productivity is "finally being recognized as a worthwhile investment and not as a drain on the resources of the country."
Fransen told conference delegates that these embryonic shifts in thinking present tremendous opportunities for the development of global "microsolutions" to better the health and economic conditions of developing countries.
One area of particular importance is in increasing official development aid (ODA) and channeling those funds from military purposes to social development. "In the last decade, public ODA has decreased worldwide, and the effectiveness of aid has been seriously questioned," she said. In very poor nations like Bangladesh, Fransen said, individuals may spend at least 10 percent of their income on private health expenses. "For households, resource allocation tradeoffs are very difficult," she said.
Goals for health improvements and poverty reduction that were set five years ago during a social development summit meeting in Copenhagen, Denmark, still are a long way from being met. But Fransen noted that a review summit planned later this year in Geneva "gives us the political and intellectual forum" to debate changes in how ODA is given and invested.
In a presentation about development assistance and debt relief, IAPAC Executive Director José Zuniga echoed Fransen's call for an increase in development assistance funding. "The economic consequences of failing to support these assistance mechanisms is a decelerated pace in achieving the eradication of conditions that contribute to human deprivation and disease, slower than necessary economic growth in developing countries, and potential economic repercussions for industrialized countries."
Zuniga argued that along with increasing support for and retooling development assistance mechanisms, there needs to be immediate attention focused on global trade and investment. Global markets are denying as much as $500 billion of market opportunities annually to resource-limited nations because of barriers to the movements of goods and people and because of the four times higher real interest rate that developing countries are paying compared to developed countries, he said. "The $500 billion loss in market opportunities exceeds development assistance levels, thus it is certainly better for the poor to be able to earn their living than to be put on indefinite international charity," Zuniga said.
Fransen, Zuniga, and other key conference presenters also agreed that shifting the view of products used to fight AIDS, malaria, tuberculosis and other communicable diseases from market-based commodities to international public goods is another important area for action. Fransen told conference delegates that the development of these public goods should be supported by direct investment from the international community. Medications and vaccines for these diseases currently attract little in investments because they are not viewed as profitable.
But international investment in these medications and vaccines as international public goods produces a worldwide benefit, Fransen said. In the future, solutions for such issues as the thinning ozone layer, global climate change, and drug trafficking may be found in the same way, she added. "This is global housekeeping, it's ensuring an adequate provision of global public goods."
But while conference delegates devoted much of their attention to the suffering from lack of resources in Third World nations of Africa and Asia, one speaker reminded them of crumbling health and economic conditions much closer to the conference venue of Vienna.
"Up to the 1970s the health status of the East European countries was comparable to that of the West, indeed in the 1970s life expectancy was higher in East Germany than in West Germany," said Alan Whiteside, PhD, of the University of Natal in Durban, South Africa.
But freedom in Eastern Europe has come at a cost. The fall of communism and its strong central control has led to shortages of consumer goods, poor quality in manufacturing, unstable employment, and health status that has deteriorated substantially in the past decade. In comparing Eastern European nations with those in the West, Whiteside said the tuberculosis rate in the Russian Federation is 75 cases per 100,000 population, 67 per 100,000 in Moldova, but 10.7 per 100,000 in the United Kingdom.
In the Ukraine, from 1987 to 1994, Whiteside said mass HIV testing was performed on a wide range of population groups-people leaving or entering the country, suspected drug abusers, prostitutes, pregnant women, and those in the military. Of 40 million tests, 398 were positive; 183 of those who tested positive were Ukrainians.
"Ukraine was not experiencing an epidemic of HIV but rather there were sporadic occurrences, mainly among non-Ukrainians," Whiteside noted. But in 1995-96, the picture was changing. In surveillance, infected Ukrainians numbered 1480 compared with only 20 non-Ukrainians who tested positive. The route of transmission now is predominantly intravenous drug use. Whiteside said that in some regions of the country where drug use rates are high, up to 18 percent of intravenous drug users are HIV-infected.
Increasing rates of HIV infection and other sexually transmitted diseases in Eastern Europe, Whiteside said, reflect behavior in a risky environment rather than the impact of individual risk behaviors alone. Society as it operated under communism, he observed, has not yet been replaced with a "civil" society in which economies, employment, and lifestyles have stabilized. The spread of HIV in the region generally is confined to intravenous drug using populations. But if the virus spreads further, Whiteside warned conference delegates, "I fear for the future of Eastern Europe."
Given the high-risk environments that exist not only in very poor African nations, but also within an hour's flight time from Vienna, conference speakers said stakeholders in the pandemic must find better ways to use existing resources.
Mike Youle, MD, of the Royal Free Hospital in London, pointed out that over the next decade, cost would not be the only barrier to obtaining the benefits of combination antiretroviral therapy. "Resistance [to ARV drugs] will be a major challenge," he said. "The virus you caught in 1989 is not the same virus you catch in 1999." As a result, clinicians will have to consider more innovative therapies—for example, using hydroxyurea to maximize the effect of nucleoside drugs, using ritonavir to push the effects of indinavir, or possibly using interleukin-2 alone.
"Resistance and cost are the scientific enemies, but apathy and inequity are the political enemies," Youle told conference delegates.
While clinicians struggle with issues of optimal therapy, non-government organizations (NGOs) and AIDS service organizations (ASOs) are beginning to consider a business-oriented approach in their operations to boost quality and avoid duplication of effort.
Joseph Scheich of the Amsterdam-based Global Network of People Living with HIV/AIDS (GNP+) said NGOs and ASOs "need to adopt a concept of joint ventures and strategic alliances." Recently, during a large conference held in Warsaw, Poland, Scheich said his organization partnered with the International Community of Women Living with AIDS. "We formed an alliance that was very successful in terms of fund-raising capacity," he explained. "Together, we were able to raise funds that we would not have been able to separately. Together, we had a more attractive package than if we had worked alone."
Some of that sentiment can be extended to the pharmaceutical industry. Peter Young, president and CEO of US-based AlphaVax, said the industry has done "excessively well" in producing new treatments for HIV/AIDS. "A number of companies should be individually applauded on their policy initiatives and the leadership they've taken," he said.
"But the corollary is that strengths reflect weakness, and that leadership also reflects a fragmented industry approach," Young said. "Each company tends to act in solitary fashion on these policy initiatives rather than fashioning a more unified approach."
Despite relatively rapid successes in new HIV/AIDS product development, Praphan Phanuphak, MD, PhD, of the Thai Red Cross Society's Program on AIDS questioned why more pharmaceutical companies in different parts of the world are not involved in the effort. After all, Young noted that new products with greater clinical efficacy and lower cross-resistance with existing drugs have become more challenging to develop. But of all the nations where pharmaceutical companies are located, Phanuphak said only Switzerland, the United States, and the United Kingdom have companies producing HIV/AIDS drugs.
But the reality is that price controls and import fees keep many companies out of the HIV/AIDS product market. "It's not a lucrative market, and it's too controversial to take the risk," said James Sapirstein, RPh, of Bristol-Myers Squibb. Effects of the poor financial profile are compounded, Sapirstein said, when governments in poor nations that could copy drugs because they do not have patent laws enforce policies not to reimburse for those compounds.
"Sometimes we wonder who is on whose side," he said. "Do the people who govern really care about their citizens?"
Citing figures from the Joint United Nations Programme on AIDS (UNAIDS) and other sources, Jeffrey Sturchio, MD, noted that in 1996, $141 million was spent on HIV/AIDS in sub-Saharan Africa. Yet according to one estimate, the developed world will spend $40 billion on the war in Kosovo and subsequent reconstruction work. "There is not enough money in all the pharmaceutical companies in the world to address that disparity," he said.
Sturchio cited another figure of $17 billion in aid and development assistance that went to Africa in 1996. In terms of the $141 million spent on HIV/AIDS, "less than 1 percent of all foreign aid to Africa in 1996 went to HIV/AIDS," Sturchio said. "The problems we've been discussing could be addressed more effectively by redirecting some of that $17 billion."
Discussions of better ways to use existing resources are incomplete without examining the lack of palliative care for patients with HIV/AIDS. One of the reasons that healthcare systems in industrialized nations neglect palliation, said Eric van Praag, MD, of the World Health Organization (WHO), is that it is not taught in medical schools. With a few exceptions in Canada, the United Kingdom, and Australia, said van Praag, "there is no chair for this in the universities, and there is no funding. The medical attitude, and it is a strong viewpoint, is that palliation means an admission of failure."
Palliative care is overlooked in developing nations because basic care is often difficult to provide, or medical professionals still view AIDS as an illness they are not responsible to treat. Donors often earmark their investments for prevention, van Praag said, because to put money into care "is like feeding a bottomless pit." And since palliation does not have a cost-benefit profile, it is close to impossible to put it high on the agenda of HIV/AIDS needs.
But now that the populations of many industrialized countries are aging, palliation is getting more attention. For example, he said, some health maintenance organizations in the United States are beginning to pay for limited amounts of palliative care. Even so, AIDS palliation is unique because patients who are very sick are not necessarily terminally ill. Medical needs in palliation for AIDS may also focus more on relief from pain, diarrhea, constipation, nausea, vomiting, and anorexia than in care for patients who do not have AIDS.
Despite strong attitudes against palliative care, van Praag said it should be discussed when HIV diagnoses are first made. "When done well, this is discussed with patients and their families so they can plan for the future and the day when palliative care and associated services will be needed," he said.
He added that the need for palliative care and how to get funding for it is addressed in meetings that WHO holds every two years with physician and nursing groups, including IAPAC, meant to examine better ways to provide humane medical care.
After a decade of research, only one candidate-the gp120 HIV vaccine-has reached Phase III clinical trials. The verdict on gp120's efficacy is not due for another two to three years, but experts warn that countries with large high-risk populations face serious consequences if they fail to start planning a vaccine strategy.
"To plan or not to plan, this is the question," said Anita Alban, an economist with the Joint United Nations Programme on HIV/AIDS (UNAIDS). "You have to understand that not planning for a vaccine will cost thousands of lives and [great setbacks in] human development."
During IAPAC's Third International Conference on Healthcare Resource Allocation for HIV/AIDS and Other Life-Threatening Illnesses, Alban sketched out scenarios in vaccine planning. Using background information from three African countries, she forecast spending and infection estimates in a composite country with a population of 26 million, including 1.5 million who are HIV-infected and 85,000 with AIDS.
In the first scenario, a useable vaccine becomes available in 2004, when $8 million to $11 million is spent on HIV/AIDS care in the country and $30 million goes toward prevention. But the country takes no immediate action, waiting to learn from the experience of neighboring nations. By 2007, she estimated, the country's population increases to 26.3 million, 1.7 million are HIV-infected, and 90,000 have AIDS. Costs for care increase to between $9 million and $12 million, and prevention costs rise to $31 million.
If the country immediately used the vaccine, Alban's projection showed that by 2007 there would be no increase in the number of HIV-infected people. But there would be 90,000 AIDS cases, the same as if nothing had been done, because those cases would represent infections that occurred many years in the past. Costs for care would increase to between $8.5 million and $11.5 million, and prevention costs would rise to $33 million.
Accounting for the time it takes HIV disease to progress to AIDS, Alban said costs for medical care will not change for eight to 10 years following the introduction of a vaccine. If access to care remains the same, she said that costs for medical care might decrease very slowly. The need for planning is so acute, Alban stressed, because countries will not simply be able to transfer the amount they spend on care to what will be needed for vaccine. In addition, countries may have to spend more on prevention when a vaccine is introduced. Because efficacy may not be 100 percent in the beginning, stepped up prevention efforts could be needed to ward off complacency that everyone is safe regardless of risk behaviors.
Alban estimated that it might take five to 10 years for countries to be able to shift resources from providing care to distributing vaccine. "This is going to mean hard work and hard preparation and investment," she said.
But financial planning is not all that is involved. "Who's going to have the vaccine first, second, and third?" she asked, describing difficult priorities. Would commercial sex workers be immunized first, for the greatest effect in stemming the spread of infection? What about those who can pay for the vaccine out-of-pocket? What about children and women of childbearing age?
Because of limited resources and high start-up costs, Alban said a country of 26 million may only be able to provide vaccine for 200,000 people. How will the remainder react if they cannot obtain the vaccine, and their country has no strategic plan for how it is distributed? "I don't know, civil war or something like that," she said. "There is a great, great need for master strategic plans on vaccine."
A great need also exists to focus vaccine research on HIV subtypes dominating high-prevalence countries in Africa. "One concern I have is that the gp120 vaccines, which are aimed at producing antibodies, may be very type specific," said José Esparza, PhD, who leads the UNAIDS vaccine team. He pointed out that a gp120 vaccine being tested in the United States is bivalent, containing two subtype B viruses from syncytial inducing and non-syncytial inducing virus. In Thailand, a bivalent gp120 vaccine containing virus from subtypes B and E is under study.
"According to the science we know today, an effective gp120 vaccine against clade B or E may not be effective against clades A, C and D that are prevalent in Africa," Esparza explained. "This is a major problem."
Despite the overall paucity of vaccine research for reasons ranging from scientific difficulty to fears of liability or poor investment returns, the European Union (EU) has stepped up its efforts in pushing for the availability of an efficacious vaccine. In meetings with various partners, including the World Bank, countries, and private industry, an EU leader told conference delegates that the private sector must take a more active role.
"We need the private sector and the countries to be involved," said Lieve Fransen, MD, PhD, principal administrator of health, development, and HIV/AIDS issues for the European Commission, which carries out the EU's HIV/AIDS Programme in developing nations.
During EU strategy-building meetings, Fransen said it has become apparent that vaccine research and strategies for rapid, widespread vaccine distribution must be tackled simultaneously. "We must accelerate the process and do it concomitantly rather than sequentially," she said. "If we do it sequentially, we will end up with a vaccine that is not widely available, and that is accessible [in developing countries] only 10 to 15 years later."
In recent months, Fransen said, the EU has developed a 10-point strategy that includes increased funding for biomedical research for an HIV vaccine, discussions on intellectual property rights, and analyses of potential vaccine markets and how public funds should be invested in them. Additional aspects of the strategy include working with analysts to help countries plan vaccine distribution priorities, and investigating whether HIV vaccine makers may be accorded the same incentives as orphan drug manufacturers.
Several critical industrial issues must be addressed to ease the way for a viable HIV vaccine in reaching markets in developing nations, said Seth Berkely, MD, president of the International AIDS Vaccine Initiative (IAVI). Even though poor vaccine quality has shut down local production in many developing countries, Berkley said it must be revitalized. "They have enormous capacity potential, especially in countries like China and India," he said.
He also explained vaccine markets' financial realities. "The vaccine market is about $3 billion to $4 billion, versus $300 billion or more for medical drugs," Berkley said. " The difference in prices for the most wealthy countries versus the poorest markets for the same vaccine is 70-fold. That's extraordinary. Only 14 percent of vaccine is sold in high-profit markets, but that makes up 75 percent to 80 percent of the actual market value. That's why vaccines for developed countries are really where the big profits are," he explained.
Given the lack of financial incentive, what conditions might lure vaccine makers into collaborations with the public sector in developing countries? Berkely ticked off a few essentials: clear decision-making paths; implementation of decisions in a set time frame; firm, long-term commitments; confidentiality, and protection of intellectual property.
"None of these are characteristic of the public sector," he observed. "The public sector has to work in open situations, and this makes collaboration difficult."
But Peter Young, president and CEO of AlphaVax, which receives IAVI funding for development of its HIV vaccine candidate, said changing conditions and attitudes may make collaborations more likely. He said some industrialized nations have begun to accept price breaks for developing nations, even if they do not openly call for price differentials. He also said that more "enabling" infrastructures for clinical trials of vaccine candidates are being developed. "This was something the industry couldn't do for itself," he said.
But he also advised the public sector in developing nations to find ways to create market environments where profits are possible but not guaranteed at set levels. If a fixed profit is established, he said, there is no incentive to distribute the product to as many people as possible.
"The last thing you want to do is to sterilize competitive risk in the private sector," he said. "Make [companies] compete on product profile and price. They thrive on beating each other to death—let them do it on your behalf."
Without widespread use of an effective HIV vaccine and because of infection rates that are ravaging great proportions of the global population in impoverished countries, HIV/AIDS public health policy experts are calling for entirely new approaches emphasizing prevention.
Attention in recent years to dramatic recoveries attributed to triple-drug therapy "perpetuates the impression that you can just take a pill and get well," said Rafael Mazín, MD, the Pan American Health Organization's (PAHO) regional AIDS advisor. "We must create a culture of prevention," Mazín told delegates at IAPAC's Third International Conference on Healthcare Resource Allocation for HIV/AIDS and Other Life-Threatening Illnesses.
For example, he noted that only 2 percent to 3 percent of national AIDS program spending in the Americas is devoted to prevention. Part of the reason that prevention still takes a back seat to treatment as the pandemic approaches its third decade is that evaluation of the benefits from prevention remains an extremely complicated endeavor.
In the time since AIDS was discovered, the developed world's emphasis on outcomes has driven choices in medical care. Therapies that are not proven in randomized, controlled trials are not widely used or reimbursed, and the effects of drug treatment are easier to evaluate in controlled clinical trials than are the effects of prevention programs.
Steven Forsythe, a lecturer at the Liverpool School of Tropical Medicine, said cost-benefit analyses that evaluate the cost of prevention per HIV infection prevented are the most effective evaluation tool that economists can use when trying to influence policy makers who will determine the implementation of prevention programs.
"Cost-benefit analyses are the most complex, but they are the most useful," Forsythe said.
"This is a difficult issue," said Stefano Bertozzi, MD, PhD, of Mexico's National Institute of Public Health. "AIDS causes other problems that cannot be captured by determining the cost of a life saved. There are many disruptions in society, and we have to come up with other ways to measure all of those other things." For example, he said, just looking at gross domestic product (GDP) growth as an indicator of the impact of AIDS on a country is a mistake. "When you look at how life expectancy is cut, it brings the issue to life," he said.
When prevention programs are implemented and HIV prevalence reductions subsequently are reported, it still is difficult to quantify the impact of the program, compared with other variables that may have caused changes in risk behaviors. "We would all like to set a goal," in reducing new infections, said John Stover of the US-based Futures Group. "But we don't know how many condoms or behavioral sessions we will need to achieve our goals."
Lieve Fransen, MD, PhD, coordinator of the European Union's HIV/AIDS program in developing countries, urged resource-limited nations to begin looking at HIV control in terms of treating other sexually transmitted diseases (STDs). She described striking results from two community-based intervention trials in Africa that are the subject of a new book published by the European Commission, "From Knowledge to Practice: STD Control and HIV Prevention."
"STDs were neglected for a long time in the developing world, until HIV came along," Fransen said. But even though evidence exists to show that treating STDs can reduce HIV incidence, "we see STDs slipping away from the agenda," she said.
In one of the trials, STD case management was carried out in eight villages in Mwanza, which is located in northwestern Tanzania. During a 2-year period from 1992 to 1994, new HIV infections were reduced by 38 percent. The other trial, which implemented the STD intervention in five communities in the Rakai district of Uganda from 1994 to 1996, produced no reduction in new HIV infections.
Reasons for the different outcomes are discussed in the book, but Fransen said the intervention in Mwanza was effective and affordable. In a population area of about 150,000 people, the cost for treatment of each STD case was about $10, which resulted in a per capita cost of about 39 cents. She said that 252 new HIV infections were prevented each year of the intervention, resulting in a cost of about $218 per infection prevented.
Since the cost of prevention is less than that of future treatment costs, Fransen said she is left with one nagging question: "why is it not being done?"
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Copyright © 2000 - International Association of Physicians in AIDS Care. All rights reserved. http://www.iapac.org
This information is designed to support, not replace, the relationship that exists between you and your doctor.