Kofi Annan describes global AIDS epidemic as one of the greatest challenges facing our generation, a global emergency - an unprecedented threat to human development requiring sustained long term commitment and action1. Over 20 million people have died while an estimated 37.8 million are living with HIV/AIDS with 50 per cent being young girls/women. In fact young people (15-24 yr) account for half of all new HIV infections, more than 6000 contracting the virus each day. Last year in poor countries HIV/AIDS killed over 3.1 million, about 8000 every day. Can we check the mortality, stem the spread of the infection, improve the quality and care of those living? Recent experience has shown that while cure remains elusive, there are other approaches with proper leadership that could definitely make a difference to “ …the most globalized epidemic in history"1. Ironically, it is the increasingly globalizing economy that is responsible to at least one critical element of the global efforts to control the pandemic. Keep most of the drugs out of reach of HIV/AIDS patients. Why the focus on drugs? According to Barry Bloom, Harvard School of Public Health, highly active retroviral therapy cuts down death rates in HIV/AIDS patients by 73 per cent2. These drugs are unaffordable to the poor patients and there are far too many of them. In December 2004, only about 12 per cent (700,000 of 5,800,000) HIV/AIDS patients from all developing and transnational countries were receiving anti-retroviral (ARV) treatment1. The relative coverage says it all - about 8-9 per cent in Sub- Saharan Africa and South East Asia and 65 per cent in the Americas. What is more, just 34 high-burden Indian J Med Res 121, April 2005, pp 211-214 Editorial TRIPS, patents & HIV/AIDS drugs 211 countries in Africa and Asia account for over 90 per cent of these. Almost 15 yr since antiretroviral drugs became available, just one of ten pregnant women receives the ART. The ARVs don’t come cheap. Cost estimates vary from US $ 150 to US$ 250 per person per year (ppy), if sourced from generic manufacturers. An estimated US $5.1 billion to US$ 5.9 billion will be needed by the end 2005 toward ART and support cost for the 3 by 5 goal of WHO and UNAIDS1. And this will cover only 3 million people in the low and middle income countries3. The 'low-cost option' estimate of US$ 5.1 billion is based on the US$ 140 ppy negotiated by the Clinton Foundation from a generic manufacturer from India3. It appears that Abbott offers an ARV combination for $500 ppy to all African countries and less developed countries (LDCs), but charges $4336 for the same drug to ten Latin American countries4. Patients in developed countries like the US pay $10,000 to $15,000 annually for the same medication2. The high cost of drugs is due to patent protection. Most of the R&D is done in the private sector and pharma companies hold almost all the patents for the ARVs. It takes an estimated US$ 500 million and 12 to 15 yr to bring a new drug to market5, and the industry needs to recoup the cost. Many commentators consider the TRIPS agreement to be responsible for the current global crisis in the HIV/AIDS drugs. ‘TRIPS’ stands for Trade-Related aspects of Intellectual Property Rights, a global treaty to ensure intellectual property rights within international trade. During 1986-94, industrialized countries led by the US pushed for a global intellectual property rights (IPR) protection system. Earlier, IP regimes were mostly left to 212 INDIAN J MED RES, APRIL 2005 national discretion in both developed and developing countries. Countries like India did not have ‘product’ patent protection for drugs and the total period of patent protection was five years from the date of sealing or 7 years from the date of filling. The objective was to harmonize the way IP is protected around the world by establishing a set of common minimum international rules designed to protect inventors (primarily from the pharma industry). After prolonged and acrimonious negotiations, TRIPS came into force in 1995. As TRIPS rules prohibit ‘copying’ a drug under patent protection (so called generics), during these negotiations, countries like India, Brazil and other poor countries continuously expressed their misgivings about the potential adverse impact of the treaty on the price of medicines, including life saving drugs, a concern shared by several international non- governmental organizations (NGOs) like Medicines Sans Frontieres (MSF), Oxfam, Third World Network (TWN), etc. The simmering debate surfaced in 1997 when the Republic of South Africa modified IP laws to provide cheaper medicines for the alarming HIV/AIDS infected population by invoking what is known as compulsory licensing provisions for patented drugs. The US and the EU threatened trade sanctions against South Africa besides initiating a protracted legal battle. In the light of severe international criticism, the US withdrew the case. About the same time, the US took on Brazil when the Brazilian govt threatened invoking compulsory licence provisions- on two patented drugs. The Lancet predicted6 that “...if the USA does not withdraw its case, the wrath of the international community will be as furious as in South Africa and make Brazil the moral winner what ever happens”. The prediction proved right and on June 25, 2001, the US withdrew its complaint against Brazil. Some concerns on the TRIPS, patent protection and their impact on global health thus continue to be in the forefront of a global debate since 1985. Some of these include (i) strong patent protection leads to higher drug prices eventually out of reach of people in developing countries; (ii) enforcement of TRIPS provisions will have a serious negative effect on the local manufacturing capacity; ( iii) TRIPS discourages R&D to produce a cheaper source of generic, innovative, quality drugs for poor countries; (iv) TRIPS provisions will not encourage adequate R&D for developing drugs and vaccines for diseases of the poor such as malaria, tuberculosis and HIV/ AIDS. Developed countries led by the US consistently opposed any dilution to the TRIPS provisions. Yet, developing countries like Zimbabwe, India and Brazil supported by international NGOs like the MSF, Oxfam, etc., pushed for discussion on the TRIPS rules and public health. Finally, in 2001 the TRIPS Council agreed to hold a special session on access to medicines. The US primarily took the US Pharmaceutical Research and Manufacturers of America (PhRMA) position7 that patents really are not the issue in access to medicines in poor countries. While these discussions were on, the tragic event of 11 September 2001 of the terrorist attack of World Trade Centre and Pentagon occurred which, some commentators, consider played a crucial role in the final outcome of the TRIPS Council debate in Geneva and the eventual outcome at Doha. Following this attack, the US and Canada perceived bio-terror (anthrax virus) threat and thus a large scale public health emergency which necessitated large supply of ciprofloxacin, a patented drug from Bayer. To bring the price down, Canada granted a compulsory license to a local manufacturer in October 2001 while the Secretary HHS, US threatened Bayer with a grant of compulsory license to a US firm if the company did not meet the demand for price reductions. Bayer was forced reduce the price to half at which it initially offered to supply the drug (See 7 for details). The action of the US was widely criticized: “It is time ..US Government recognized … that public health needs may have to override trade profits, and that putting money into a fund while doing its utmost to prevent life-saving treatments reaching those who need them is duplicitous. The US .. should apply the same standards in defining what is, or not, a public health emergency”8. The Doha Ministerial meeting (9-14 November 2001) is possibly the first time the issue of public health was discussed in close association with a country’s development at every level of the WTO system. The Doha Declaration on the TRIPS Agreement and Public Health9 is also considered the first real victory for the poor countries in the 20 yr 213 history of TRIPS. The Declaration restated and affirmed the right of Member States to take measures to protect public health, clarified certain controversial obligations contained in the TRIPS text and tried to provide assistance to developing countries and LDCs in resolving devastating public health crises like HIV, tuberculosis, etc9. While the Doha round tried to address and clarify several contentious issues in TRIPS, it did not resolve the raging debate on patent protection in the developing world but left the highly contentious issue of compulsory licensing unresolved to date (See 10, 11 for details). A public health crisis of this unprecedented magnitude needs solutions within and outside the TRIPS regime. Solutions for the control of HIV/AIDS need to be found within and outside the TRIPS agreement. While factors other than patent protection play a role, trade ministries and the pharmaceutical industry need to rise above mere profit making and consider the ethical and moral need to provide poor HIV/AIDS patients with life-saving medicines. And access to medicines should have primacy over commercial interests. As a starter, the Doha Declaration and all the TRIPS "flexibilites" for least developed countries should be implemented in letter and spirit (See 10, 11 for details of implementation issues). WTO is not the primary international institution for addressing public health needs of developing countries which makes the role of UN agencies like the WHO and UNAIDS, Global Fund etc., most critical (For discussion, See 7). In a report prepared for the US Congress, Thomas2 proposed some interesting legislative and other options that could be considered by the industrialized countries. A differential pricing system that envisages companies with patented drugs to recover most of the costs in the developed world and at the same time license or sell at lower prices in the poor countries is one such. Perhaps licensing out to a company in developing country for manufacture could be a better option as local manufacturing would ensure sustainability and lowest price besides strengthening local technical competence12. In 2001, GlaxoSmithKline Plc handed over rights to its AIDS medicines to Aspen Pharma Care in South Africa13. In exchange, Aspen will pay 30 per cent of net sales to one or more NGOs fighting HIV/AIDS in South Africa. The UK Government has recommended to the WTO to explore means by which voluntary licensing could be made more wide spread to promote access to medicines14. Another option put forth by Yale economist Jean Lanjouw envisages market segmentation wherein drug companies choose whether to procure or enforce patents in either the developed or the developing countries2. This policy takes advantage of the US patent laws that require pharma companies that perform R&D in the US to seek the so called ‘foreign filing license’ from the USPTO before filing foreign patents2. It should also be possible for all the players- government, industry, UN agencies and donors to sit across and negotiate patent and royalty issues for ensuring availability of HIV/AIDS drugs in poor countries. The MSF has also proposed 15 (i) encouraging generic competition; (ii) differential pricing of drugs; (iii) adopting TRIPS safeguards into national legislation; (iv) creating high volume/high demand through global/regional procurement; and (v) encouraging local production through voluntary licensing and technology transfer. But even at the 'low- cost option'3, there is still a short fall of US $ 3.5 billion to scale up ART access to 34 hardest hit countries1 even at the first line treatment. There should be a thrust for encouraging R&D in both the private and public sectors. The pharma industry considers R&D on drugs for diseases of the poor to be uneconomical. Steps as supporting R&D in selected diseases, tax credits on R&D spend and similar incentives to encourage industry participation should be stepped up. Efforts already on to set up public-private partnerships wherein the pharma works closely with public sector institutes for the discovery of new drugs, vaccines and diagnostics for HIV/AIDS should be further strengthened. In the long term, at the global level, there is an acute need to put in more money for R&D. According to the Global Forum for Health Research16, the global expenditure on R&D on health is quite inadequate. Of the US$ 105.4 billion spent on health R&D in 2001, SATYANARAYANA: TRIPS, PATENTS & HIV/AIDS DRUGS 214 INDIAN J MED RES, APRIL 2005 the total private sector investment was as much as 56 per cent, with the Private-for-Profit sector accounting for almost 50 per cent underlining the need for enhanced investment for health R&D both in the developed and developing countries. The R&D spend by the public sector in poor countries was a miniscule 2.4 per cent. This is especially significant as drug R&D targeted at infectious diseases has virtually ground to a halt; drug companies are simply not interested in R&D for diseases that abound in developing countries17. Of the 1,223 new drugs approved between 1975 and 1997, just 1 per cent (13 drugs) specifically target tropical diseases18. Annan says1 that if there is one lesson that the 20 yr old epidemic has taught, it is: “…we can make a difference; we can prevent new infections and we can improve the quality of care and treatment for people living with HIV”. Availability of affordable anti-retrovirals should be the heart of future global strategy. And the time to act is now. K. Satyanarayana Chief, Intellectual Property Rights Unit Indian Council of Medical Research New Delhi 110029, India e-mail: kanikaram_s@yahoo.com References 1. Report on the global AIDS epidemic (Geneva,WHOUNAIDS) 2004. 2. Thomas JR. HIV/AIDS drugs, patents and TRIPS agreement: Issues and options. CRS Report for the US Congress July 2001. 3. Gutierrez JP, Johns B, Adam T, Bertozzi SM, Torres Edejer TT, et al. Achieving the WHO/UNAIDS antiretroviral treatment 3 by 5 goal: what will it cost. Lancet 2004; 364 : 63-4. 4. 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Marquette Intellect Prop Law Rev 2004; 8 : 211-50. 12. t’Hoen E. Affordable medicines for developing countries. WHO/WTO Workshop on differential pricing and financing of essential drugs (Hosbjor, Norway, 8-11 April, 2001). 13. Glaxo gives up right to drugs in South Africa. Reuters New Media, October 6, 2001 (www.aegis.org; accessed on March 21, 2005). 14. Access to medicines in the developing world. Postnote July 2001 (Parliamentary Office of Science & Technology, UK) (www.Parliament.uk/post/home.htm. Accessed on March 21, 2005). 15. T’Hoen E Moon S, Pecoul. Pills and pocketbooks: Equity pricing of essential medicines in developing countries. WHO/ WTO Workshop on Differential pricing and financing of essential drugs, Hosbjor, Norway, 8-11 April, 2001. 16. Monitoring financial flows for health research , vol 2. Geneva: Global Forum for Health Research; 2004 17. Pécoul B, Chirac P, Trouiller P, Pinel J. Access to essential drugs in poor countries. A lost battle? 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