Even before activist protests made headlines last summer, the debate over international access to AIDS drugs had become deeply polarized. Health advocates argued that people in developing countries could not afford to buy AIDS drugs at full, industrial-market prices. Pharmaceutical companies countered by defending the importance of patent rights and claiming that the health care infrastructure in many countries could not deliver drugs even if they were provided free.

Unfortunately, there is enough wrong with the international drug and vaccine delivery systems for both sides to be right. In the long run the private sector needs some intellectual property (IP) protection if it is to invest resources, yet respect for IP agreements is ultimately not sustainable unless credible plans for access to life enhancing drugs are put in place.

The reasons for limited access to AIDS drugs in developing countries are many and complex, and the raging debate on this issue foreshadows similar controversy on access to AIDS vaccines. History provides ample reason for concern that when an AIDS vaccine is finally available, it will sooner protect people in rich countries than those in the poor areas of the world where the epidemic is spiraling out of control. Hepatitis B, for example, kills approximately one million people annually, yet the Hep B vaccine, first licensed in the early 1980s, was not purchased by international aid agencies until more than a decade later. Even today, Hep B vaccine is not delivered in many poor countries. Another example is the Haemophilus influenzae type b (Hib) vaccine, which could potentially save half a million children each year - yet it remains unavailable in many countries of the developing world 13 years after being licensed.

Purchase of future vaccines may be even more challenging. With current vaccine research employing expensive new technologies, initial prices of new vaccines against AIDS or any other disease may be significantly higher than those for Hep B and Hib.

But why address the thorny issue of access now, when a licensed AIDS vaccine is still years away? The answer is that a credible plan to purchase and deliver an AIDS vaccine affects critical decisions being made today. Absent a clear plan for purchase of AIDS vaccines for the world's poorer countries, there is little incentive for industry to invest in developing vaccines appropriate for these populations or to build manufacturing plants that can produce them fast enough to meet the anticipated demand. Likewise, other access-related issues also require years of pre-planning if they are to be resolved by the time an effective vaccine is ready.

If the story with AIDS vaccines is to be any different than that of Hep B or Hib, public and private sector leaders must begin working now to design a comprehensive system - from the patent office to the rural health clinic - that can improve vaccine delivery. Many ideas for assuring access to AIDS vaccines have been proposed, and they address multiple stages of the product development and delivery pipeline. These include:

• Delivering existing vaccines: A first step in being able to deliver AIDS vaccines is to do a better job of delivering vaccines that are already available, such as those for Hib, Hep B, and yellow fever. One effort along these lines is the Global Alliance for Vaccines and Immunization (GAVI), which is working to improve immunization systems in developing countries. If it succeeds, GAVI will provide immediate health benefits for the developing world and demonstrate to vaccine makers that the international community is able to effectively purchase and deliver pharmaceutical products.
• New purchasing mechanisms: Novel financing schemes that guarantee a paying market for AIDS vaccines would expedite purchase of these products and therefore provide an incentive for industry to accelerate research on vaccines appropriate for the developing world. There are several worthy proposals that urgently need political support. However, it is important to realize that none of them would, by themselves, secure rapid purchasing of AIDS vaccines for all lower and middle-income populations, and that a range of purchasing mechanisms will therefore be needed.

Another approach is now being widely discussed in U.S. government arenas. One proposal was made by U.S. President Bill Clinton who, in his final State of the Union address, called for a tax credit on the sale of vaccines for malaria, TB, and AIDS. Administration officials hope such a credit would entice more industry research on these products and help promote the sale of vaccines for the developing world. Legislation now pending in the U.S Congress would provide an even broader range of research and access incentives. The Vaccines for the New Millennium Act, introduced by Senator John Kerry and Representative Nancy Pelosi, would create a purchase fund in the U.S. Department of Treasury for vaccines against AIDS, TB, and malaria, and would direct the President to negotiate for creation of a multi-lateral vaccine purchase fund. (See IAVI Report, April-June 2000.) The bill also includes Clinton's vaccine tax credit.

Yet another idea comes from Harvard economics professors Jeffrey Sachs and Michael Kremer, who proposed a system of purchase pre-commitments for HIV, TB and malaria vaccines. Countries would pledge to fund purchase of these vaccines when they become available, and an international body would enter into negotiations on vaccine purchase and pricing. The Sachs/Kremer proposal calls for funding of individual country accounts that would give developing countries a role in deciding whether or not to purchase vaccines for their populations.

Each of these purchasing proposals raises the question of credibility. Will industrial-world governments keep their pledges to purchase vaccines for lower income countries once a product is available? Will developing world government leaders take advantage of low interest loans or specially created accounts to buy AIDS vaccines? Perhaps legally binding commitments can strengthen government commitments. Ultimately, sustained political pressure from health leaders, advocates, and the public will be needed if such new purchase mechanisms are to be effective.

• Market based (or tiered) pricing: Differential pricing is a common practice in many industries, from airlines to vaccines. Vaccine buyers in industrialized nations are generally charged a "market" price that factors in R&D costs and profit, while purchasers in middle income countries and buyers for the poorest countries are offered much lower rates. Yet, although market-based pricing will be essential if AIDS vaccines are to reach poor countries, some vaccine makers have concerns about this approach. Some politicians in the U.S. have questioned why their constituents pay what they see as a premium price for drugs. With the pharmaceutical industry under growing scrutiny in the U.S., simultaneous multi-tiering of prices for an AIDS vaccine may be politically difficult.

• Intellectual property agreements: Agreements between funders, researchers and vaccine manufacturers early in the vaccine development process can accelerate access to a licensed vaccine. For example, in its vaccine development partnerships, IAVI has secured commitments from biotechnology companies that will help a successful vaccine be distributed in lower income countries at a reasonable price. Should a company decline to produce the vaccine for lower income countries in reasonable quantity at a reasonable price, IAVI has certain rights to contract with other manufacturers to make the vaccine available in those countries.
• Manufacturing plants: The production capacity of vaccine manufacturers dictates how many people receive a vaccine, and how soon. Difficult decisions about plant size need to be made relatively early in the research process, even before vaccines have been licensed for use. Private sector vaccine makers typically design a plant to meet the immediate need in industrialized markets; only years later, when that initial demand is met and companies have recouped their investment and made a profit in industrial country markets, is the vaccine produced for the developing world and sold at much lower ("marginal") cost. The public and non-profit sector could promote expanded vaccine production capacity by guaranteeing to purchase vaccines at an attractive price, or by helping to finance construction of manufacturing facilities, in exchange for promises of early bulk sales of vaccine at very low prices.

• In-country demand and infrastructure: In a 1999 report, the U.S. General Accounting Office identified factors limiting availability of vaccines to children in developing countries, including inadequate health care infrastructure and insufficient information about disease burden and the cost-effectiveness of vaccines. With respect to AIDS vaccines, such issues must be addressed quickly if these products are to be made widely available immediately after licensure. Concerns about health care infrastructure are especially complex given that AIDS vaccines will initially need to be provided outside of the existing childhood immunization system, and to target the sexually active teenagers and adults most urgently in need of protection from HIV.

Each of these proposals raises questions that need attention. How will an AIDS vaccine purchase and delivery system work if a series of different vaccines are licensed over several years? With nearly six million new HIV infections annually, how will public health agencies decide whether to purchase a vaccine that is 30% effective if they believe that a vaccine with 60% efficacy is two years down the road? What standards will be used to set prices of an AIDS vaccine, knowing that a high price could drain precious resources but a very low one could slow vaccine production and dampen research and development on improved vaccines? How can advance promises to purchase AIDS vaccines be made credible to vaccine manufacturers?

At this stage in AIDS vaccine research, access may seem like a distant problem. Yet if the international community does not quickly and comprehensively address access issues, the result will be an AIDS vaccine that benefits a lucky few but fails to bring the international epidemic under control. The complexity of the issues, and the immediate positive effects that credible vaccine purchase and delivery plans would bring, mean that tackling the access challenge should be a top priority today.