April 11, 2007

April 11, 2007 – Doctors Without Borders/ Médecins Sans Frontières (MSF) is increasingly frustrated by the crisis faced by people living with HIV/AIDS in Thailand and throughout the developing world who need vital second-line medicines. What is even more disturbing is that this crisis comes at a time when millions around the world still have limited or no access to first-line medicines. MSF urgently seeks to avoid repeating the situation that many people faced in the late 1990s, when unconscionably high prices for antiretrovirals (ARVs) condemned many to death simply because they could not pay for life-saving medicines that were widely available in the developed world.

Since the late 1990s MSF has been providing health services to people living with HIV/AIDS in resource-poor settings, particularly in Africa and Asia. At the time we began our programs, there was a cynical conventional wisdom that poor people would never have access to Highly Active Anti-Retroviral Treatment that was available to people in the developed world. At the time, a year's supply of patented first-line medicines cost between $10,000 and $15,000. Today, the lucky few who MSF reaches are under threat again for similar reasons.

The availability of quality low-cost generic ARVs in early 2001 meant that MSF and others could finally begin treating people with the disease. As a result of this generic competition, a course of first-line treatment for HIV is now less than $150 per patient per year. The use of generic medicines has been critical to the scale up of treatment programs worldwide such as the President's Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund for AIDS, TB, and Malaria. It has allowed more than 1.3 million people to be placed on treatment today, or nearly 25% of the people living with HIV/AIDS needing ARVs in developing countries.

MSF currently provides treatment to more than 80,000 people living with HIV/AIDS in over 30 countries. In one MSF project in Khayelitsha, South Africa, 20% of patients needed to be switched to a second-line regimen after being on treatment for five years because of natural resistance that develops. While the needs for second-line regimens are likely to increase in the coming years, medicines used for second-line therapy are mostly unavailable or unaffordable in developing countries.

The Case of Efavirenz: How a Compulsory License Improved Access to a Crucial Aids Drug in Thailand

In Thailand, issuing a compulsory license has already been shown to increase access to an essential first-line AIDS drug. Efavirenz, marketed by Merck, is recommended by the WHO because it has fewer side effects than nevirapine (which is part of the fixed-dose combination 3TC, d4T, nevaripine, produced by the Thai governmental pharmaceutical company GPO as GPO-vir.) Nevaripine is associated with many toxicities including hepatoxicity, and nearly 20% of patients develop adverse drug reactions to GPO-vir and need an alternative. Efavirenz can also be used to treat people co-infected with HIV and tuberculosis (TB), while nevirapine negatively interacts with TB drugs.

Prior to issuing a compulsory license in November 2006, only those suffering from the most severe side effects received efavirenz. (In contrast, in 2004 efavirenz was the most prescribed first-line ARV in the US, representing 65% of all NNRTI prescriptions.) After the CL was issued, Thai health authorities could purchase a WHO pre-qualified generic form from Ranbaxy, and the price dropped from 1400 baht per patient per month to 650 baht per month (~US $43 to US $20) More than 66,000 bottles were imported on January 5, 2007, which will last for 3-4 months and allow health care providers to treat at the same cost an extra 20,000 patients with efavirenz.

In results released at the 14th Conference on Retroviruses and Opportunistic Infections (CROI) in Los Angeles, MSF demonstrated good clinical outcomes for second-line antiretroviral therapy (ART) in resource-poor settings. This was despite several obstacles, like the lack of access to the best regimens and the fact that patients tended to go on second-line treatment much later than in developed countries. The horrible truth is that patients might die before they even get a chance to switch to a second-line regimen because newer medicines remain unaffordable and largely unavailable in affected countries.

Heat-Stable Lopinavir/Ritonavir: Not for Poor Patients

Lopinavir/ritonavir is a vital second-line therapy needed in our HIV/AIDS programs, and the new heat-stable formulation has a number of advantages in resource-limited settings. Most important is the fact that it does not require refrigeration. For more than a year, MSF has been trying to increase access for our patients and others in the developing world to the new heat-stable formulation of lopinavir/ritonavir, marketed by the Chicago-based Abbott Laboratories as Kaletra/Aluvia.

The heat-stable version was registered for sale in the US in October 2005. In August 2006, Abbott announced a price for the new heat-stable formulation of US$ 500 per patient per year for Africa and least-developed countries. The company also announced a price of US$ 2,200 per patient per year in low-income and low-middle income countries, such as Thailand, which, must be noted, far exceeds what most people there can afford.

Since then, though, Abbott has failed to provide any information in response to MSF's repeated requests for a registration status update. So without registration, these discounted prices only exist on paper. And by withdrawing registration in Thailand in retaliation for the country issuing legally recognized compulsory licenses, patients will ultimately pay the price. When companies have monopoly-like powers over medicines, there are no obligations to register drugs or make them available.

Abbott did agree to sell the medicine to MSF for use in projects in Guinea, Malawi, Ivory Coast, Zimbabwe, South Africa, DR Congo, and Myanmar. But because the drug is not registered in most of the countries where we work, our teams need to go through time-wasting bureaucratic exercises to obtain special authorizations to import the drug.

The Second-Line AIDS Crisis in Thailand

MSF has worked in Thailand since 1976, and began providing ARV treatment to people with HIV/AIDS in 2000. Until recently, MSF was treating thousands of people living with HIV/AIDS at projects in 3 district hospitals and one pediatric program in a provincial hospital. Responsibility for treatment was handed over to the Ministry of Health in late 2006. Today, one MSF project in Mae Sot focuses on providing ARVs to 77 multidrug resistant (MDR) TB patients who are co-infected with HIV. MSF also supplies ARVs for some 260 patients in Bangkok, which includes patients on first-line treatment who are not eligible for the government program as well as patients on second-line treatment.

MSF has witnessed the development of the Thai AIDS treatment program. Generic production is the cornerstone of Thailand's universal HIV/AIDS treatment program. Before generic production, the cost of standard HIV/AIDS treatment in Thailand was more than 33,330 baht per patient per month (US $924), and only 3,000 people were getting treatment. Today, nearly 100,000 people are on ARVs, while approximately 100,000 more require it.

Both the WHO (in August 2005) and the World Bank (in August 2006) predicted dramatically rising drug costs in Thailand because of the second-line crisis. The average cost of second-line regimens in Thailand is estimated at 270,000 baht (USD $6,740), or roughly 14 times more than the average first-line regimen. The World Bank identified the use of compulsory licenses to produce less-expensive generic medicines as a strategy the government could use to address the rising costs associated with continued universal coverage for HIV/AIDS treatment to the estimated 200,000 people who need ARVs.

Since issuing a compulsory license for the heat-stable form of lopinavir/ritonavir, price reductions have already been announced. The Indian manufacturer Cipla announced on March 1, 2007, that a generic heat-stable lopinavir/ritonavir was available at a cost of US $1,560 per patient per year. Then on April 10, Abbott announced a reduced price of US $1,000 for low- and middle- income countries like Thailand only if they renounce the use of compulsory licenses. It is unfortunate that this reduction only came in response to the issuance of a compulsory license and not because of patient needs. It is obvious, though, that the compulsory license could encourage competition among multiple sources of production and help further drive down the price of this critical medicine.

Competition and TRIPS Flexibilities to Address the Second-Line Crisis

In MSF's experience, competition and multiple producers are crucial to improving access to essential medicines in the developing world. While segments of Thailand's population may be able to afford medicines priced at levels comparable to those charged in developed economies, the majority cannot. When companies use monopoly pricing strategies aimed at high income markets in low and middle income countries, then it is important to use safeguards and flexibilities like compulsory licenses. The Doha declaration, signed by all World Trade Organization (WTO) members, clearly states that the TRIPS agreement "does not and should not prevent members from taking measures to protect public health."

It is important to point out once that compulsory licenses are legally recognized means to overcome the barriers created by monopolistic pricing practices. Issuing compulsory licenses does not revoke a patent, as they are time-limited and the patent owner receives a royalty. The Thai government, for example, says they will pay 0.5% royalties for the non-commercial use of the patented medicines.

All governments in the WTO, including the United States, agreed to as much at Doha, clearly stating` that "Each Member has the right to grant compulsory licenses and the freedom to determine the grounds upon which such licenses are granted." The United States has issued five since July 2006, for everything from satellite TV technology to medical devices. Ironically, Abbott Laboratories benefited when they were designated the third party in a compulsory license ordered by the Federal Trade Commission (FTC) in 2005 on the rapid-exchange delivery system for drug-eluting stents (DES).

A number of drug patent disputes are breaking out throughout the developing world, including Novartis' lawsuit seeking to overturn public health protections in India's patent law and Abbott's harsh move in Thailand to withdraw registration of new medicines. These tactics raise the question: What good are the flexibilities built into international trade agreements if countries will be penalized for using them? And with the second-line AIDS crisis already here, all such flexibilities will be needed to provide people living with HIV/AIDS the medicines required for their survival.

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