Selection of drugs for hiv/aids care

HIV/AIDS medicines pricing report Setting objectives: is there a political will? Carmen Pérez-Casas Rapport publié le 6 juillet 2000 par Médecins Sans Frontières Document en provenance du site internet de Médecins Sans Frontières Tous droits de reproduction et/ou de diffusion, totale ou partielle, sous quelque forme que ce soit, réservés pour tous pays, sauf autorisation préalable et écrite de l'auteur et/ou de Médecins Sans Frontières et/ou de la publication d'origine. Toute mise en réseau, même partielle, interdite. HIV/AIDS medicines pricing report.
Setting objectives: is there a political will?
Author: Carmen Pérez-Casas, Co-authors: Daniel Berman, Pierre Chirac, T. Kasper, B. Pécoul, I. de Vincenzi and T. Von Schoen Access to Essential Medicines Project Médecins Sans Frontières ABSTRACT

: Ninety five percent of people with HIV/AIDS live in developing countries, and the
vast majority of them do not have access to medicines that are prolonging and improving the lives of
people with HIV/AIDS in industrialized countries. METHODS. This report compares institutional
prices of 10 essential drugs for HIV/AIDS in 8 countries and examines the affect on prices of generic
availability and patent status. Justifications for high prices of originator branded products including
the role of government in R&D, and time-to-approval, are also explored. RESULTS. According to
analysed data, the minimum price for AIDS drugs in the countries studied is, on average 82% less
than the US price. Price differences have significant repercussions. For example, the report points out
that it costs the Brazilian public health system the same amount to treat 1,000 people living with
HIV/AIDS per month as it does the Ugandan government to treat 228 individuals. DISCUSSION.
The widely divergent prices found, puts into question current drug pricing and highlights the lack of
transparency with regard to the relationship between production costs and prices. On the other hand, it
is clear that competition from the generic industry, and international institutions involvement, leads to
dramatic reductions in prices. RECOMMENDATIONS. There are several mechanisms to improve
access to more affordable drugs, even if the country in need is already compliant with the TRIPS
agreement. Available information suggests that it is feasible to bring yearly treatment cost with ARVs
down to US$200 per patient, per year, in developing countries. The conclusion to the report is that the
means to dramatically reduce prices are within reach, but what is needed is the political will to
mobilise resources on a global scale.
Table of contents

References p.19 ANNEXES Annexe Annexe 11. Zidovudine + lamivudine (AZT + 3TC) LIST OF TABLES

Table 1: Priority treatments
accessibility p.7 Table 2: Best price found for drugs produced by reliable manufacturer's, in US$ Table 3: Comparison of 1999 vaccine prices per paediatric dose, US domestic vs PAHO prices Table 4: Comparison of 2000 contraceptive prices, US domestic vs UNFPA prices


Table 1: Institutional price for ceftriaxone 1g vial, in US$
Table 2: Institutional price for ciprofloxacin 250mg tablet, in US$ Table 3: Institutional price for didanosine 100mg tablet, in US$ Table 4: Institutional price for efavirenz 200mg capsule, in US$ Table 5: Institutional price for fluconazole 200mg capsule, in US$ Table 6: Institutional price for lamiduvine 150mg tablet, in US$ Table 7: Institutional price for nevirapine 200mg capsule, in US$ Table 8: Institutional price for stavudine 40mg capsule, in US$ Table 9: Institutional price for zidovudine 100gm capsule, in US$ Table 10: Institutional price for zidovudine/lamiduvine 300/150mg capsule, in US$ A. INTRODUCTION

The lack of access to effective drugs in developing countries is part of a greater HIV/AIDS
public health crisis. Ninety five percent of people with HIV live in poor countries, and the vast
majority do not have access to medicines that could prolong and improve their lives.
In countries hardest hit by the HIV epidemic, life expectancy is 10 years lower today than at
the beginning of the epidemic, and child mortality is expected to more than double in the next
few years. Some 13 million children around the world have lost their mother or both parents
to AIDSThe disease is also decimating young adults, the engine of developing country
economies. In Malawi, for example, nearly a third of the country's school teachers are infected
with HIV.
Since the launch of Protease Inhibitors (PIs) in 1996, triple therapy - 2 Nucleoside Reverse
Transcriptase Inhibitors (NRTI) + 1 PI - has led to a reduction of mortality among people with
AIDS. Triple therapy with 2 NRTI + 1 Non Nucleoside Reverse Transcriptase Inhibitor
(NNRTI) have shown similar levels of efficacy. "Data from the US illustrates that highly
active antiretroviral therapy has reduced AIDS-related mortality by 75% and morbidity by
73% over a period of 3 years".ut the price of these treatments is such that only AIDS
patients from industrialized countries can be treated. Yearly treatment cost ranges between
US$10,000-US$15,000. GDP per capita in developing countries ranges from US$140 to

Médecins Sans Frontières (MSF) has so far mainly been working on the prevention of
HIV/AIDS, but now recognizes that it is essential to move into treatment that would allow
people to live healthier and longer lives and continue to contribute to their families and
society. Treatment also strengthens preventive efforts by increasing peoples' willingness to
get tested. In turn, once people know their status they tend to adopt safer behaviours. With
increased knowledge about HIV, the stigma surrounding the disease also declines.
However, doctors need drugs to care for HIV-infected people. Without them they are simply
managing decline and death. These drugs must be available, affordable, and properly used.
While rational drug use is still a major challenge, the goal of access to affordable medicines is
an issue of growing concern.
The World Health Organization (WHO) updates and publishes a Model List of Essential
Drugs (EDLevery two years. One of the criteria for inclusion on this list is reasonable price.
A number of clearly essential drugs, including those for treating HIV/AIDS, have not been
included mainly because of their prohibitive cost.
Which drugs are essential for HIV/AIDS in developing countries?
Advanced HIV-disease is a complex syndrome that presents a variety of symptoms and
medical conditions, many of which are manageable with drugs. The classes of drugs most
important to people living with HIV are:
• anti-infective agents to treat or prevent opportunistic infections (OIs);
• palliative drugs to relieve pain, physical and mental discomfort;
• antiretrovirals (ARVs) to limit the damage that HIV does to the immune system and to
prevent mother-to-child transmission (MTCT).
MSF has developed certain criteria, linked both to available scientific data and MSF field experience, for the selection of drugs that are essential for HIV/AIDS care in developing countries. These are: • Drugs effective in the prevention and treatment of life-threatening and frequent OIs (seen in >5% of AIDS patients in Africa, Asia or South America): - tuberculosis; - oesophageal candidiasis; - bacterial infections; - toxoplasmosis; - pneumocystic infections; - cryptococcosis; - cryptosporidiosis-isosporiosis; - penicillinases (South-East Asia). - drugs currently recommended by WHO/UNAIDS for primary prevention of opportunistic infections are isoniazide and cotrimoxazole. • Palliative drugs that significantly improve the well-being of patients such as antalgics and anti-diarrheal drugs. • Antiretrovirals that can be used in drug combination regimens in limited resource settings (which can easily be prescribed and monitored on a clinical basis and with simple laboratory tests). Easy administration is an additional justification to include a specific drug (e.g. AZT/3TC combination, plus efavirenz). • Compounds to prevent mother-to-child transmission (AZT, NVP) and to use as post- exposure prophylaxis (AZT+3TC). Drugs excluded from the priority list are: − Those which are too complex to administer and monitor, or that have limited efficacy. These criteria exclude drugs used for atypical mycobacteria, cytomegalovirus, Kaposi's sarcoma, lymphoma treatment drugs and PIs. − "Third-line" drug choices (e.g. pentamidine) where first- and second-line drugs are included and expected to be effective in the vast majority of cases.

Which drugs are priorities? Where should the battle be focused?
There are two categories of drugs for which efforts should be mounted in countries most affected
by AIDS:
1. old drugs for which the availability of cheap generics is limited;
2. drugs under patent in countries where pharmaceutical product patents are in force.
Drugs for prevention
Palliative care
and/or treatment OIs
No price-linked cotrimoxazole
anti-inflammatory drugs carbamazepine/amitripty 1st line TB drugs 1st line antibiotics miconazole or nystatin diazepam loperamide non-morphinic antalgics (tramadol) generics
ceftriaxone itraconazole pyrimethamine-sulfadiazine-calcium folinate First patent still
didanosine (ddI) valid in country
of origin
lamivudine (3TC) nevirapine (NVP) stavudine(d4T) zidovudine (AZT) AZT/3TC combination This report presents a limited comparative analysis of drug prices and patent status in a few selected countries. The role that the public sector has played in the discovery and development of each product is also reviewed, as is global revenue for each of the branded products. 1 In the US, albendazole benefits from exclusive marketing rights as an orphan drug until 11 June 2003. B. METHODOLOGY This report examines drugs that are patented in many countries, such as ciprofloxacin, didanosine, efavirenz, fluconazole, lamivudine, nevirapine, stavudine, zidovudine and zidovudine plus lamivudine. It also looks at ceftriaxone, which is no longer patented in most countries, but still remains expensive. For each drug listed, a comparison is made between its US price and its price in the eight countries where data was collected. These countries were chosen to exemplify the impact on prices when generic alternatives to originator brand products are available. Comparing prices between countries is inherently difficult because of: the problem of comparing official exchange rates and real currency values; differences in pharmaceutical distribution channels (private versus public sector, retail versus wholesale); different strengths and pharmaceutical dosages; price fluctuations over time, etc. Prices used in this study are defined as "institutional prices" meaning the non-commercial price (amount paid for a drug by a public or non-profit institution and/or NGO). Whenever possible, prices are expressed to the first decimal point, for ease of comparison. The institutional price is only part of the picture. Many people access drugs through the private sector and pay higher prices. For example, in South Africa, most people buy their daily dose of fluconazole from the private sector where it costs US$21.4, instead of the public tender price of US$ 4.1 used in this report. Annexes 2 to 11 at the end of the document present the following information for each drug: therapeutic class, indication, inclusion on WHO's Essential Drug List or argument for future inclusion, patent status, world sales of the originator's brand drug and examples of alternative sources of supply. C. DATA PRESENTATION

Table 2 summarizes the findings for each country and drug. Complete data for each drug is
presented in the annexes. Prices presented are not necessarily the lowest found in each
Table 2: Best price found for drugs produced by reliable manufacturers, in US$
Ceftria- Ciproflo- Didano- Efavi- Flucona- Lamivu Nevira- Stavu- Zidovu- Zidovu-
200 mg 150 mg 200 mg 40 mg 100 mg +lamivu-
capsule capsule capsule capsule capsule N/A N/A 0.5
2.3 N/A 0.8
0.05 0.8 3.3
4.3 2.4 0.7
1.8 0.05 2.3 3.4 0.6
2.4 N/A 4.2 0.4 3.9
N/A 0.6 0.5
0.6 0.2 0.9
1.7 0.06 0.7 2.7
2.5 3.5 0.4 0.2 2.3
1.3 N/A *1.3 1.6 *4.7 3.1 0.7 3.7 N/A 3.40 1.8 4.4 12.2 4.5 4.9 4.9 1.7 9.8 (wholesale price) Price differential: US vs best price Price 98% 72% 48% 98% 89% differential: US vs best price (%)
Prices of drugs produced by a manufacturer other than the originator of the brand drug are
highlighted in bold.
N/A indicates that prices were not available at the time this report was written.
* non-institutional prices
1. Different prices in different countries
The minimum price in the developing countries studied is, on average, 82% less than the US
price, as a result of the availability of generic products. If we exclude efavirenz from this
calculation, for which no generic was identified, and nevirapine for which only one generic was
identified, the average reduction is of 90%. Therefore, in most cases, even if prices were
reduced by 85% (as has been offered by some pharmaceutical companies), they would still not
be lower than the prices currently offered by generic producers.
There are also remarkable differences in the prices charged for originator's brand drugs in
different countries. For example, Diflucan®'s price (Pfizer's 200 mg fluconazole capsule) in
Thailand is nearly 49% less than in Guatemala (US$6.2/US$11.9). Another example is
Rocephine® (Roche's 1 g ceftriaxone vial) which is 33% less expensive in Colombia than in
South Africa (US$7.2/US$10.9).
It is clear from this report that for many treatments companies sell the same product at very
different prices in different countries. The existence of market monopolies is the single most
important determinant of these differences.
Other factors influencing national prices include: tariffs and taxes, price controls, government
price negotiations and mark-ups.
2. Impact of competition on prices
Fluconazole is not patented in Thailand. Before fluconazole was produced as a generic in 1998, Pfizer sold it for US$7. per 200 mg capsule. Three Thai companies began production and Pfizer dropped its price to US$3.6, even though generic companies were charging much less. For example, in August 1999, Biolab was charging US$0.6. After initially responding to generic competition, Pfizer increased its price in Thailand back up to US$6.2 in March 2000, while Biolab's price decreased to US$0.3 (20.7 times cheaper than Pfizer's price). This dramatic price reduction means that fluconazole is now readily available to patients. Solely because of the price change, cryptococcal meningitis has become a treatable illness in Thailand. Multinational companies have had to contend with similar competition from Cipla in India. Glaxo Wellcome's lamivudine (3TC) 150 mg tablet costs 78% less in India than in the US. This is their lowest price identified in this report. One of the most striking examples of what is possible comes from Brazil. Locally produced ARVs are sold at a fraction of their global prices. A generic form of zidovudine is 14 times cheaper in Brazil than in the US Graph 1. Prices of Brazilian Antiretrovirals
Price stability without generic competition
Average reduction: 9% (without IDV in 2000 when it was generic) Source: UNAIDS, Brazilian Department of Healthvi,vii Graph 2. Prives of Brazilian Antiretrovirals
Price reduction from generic competition
Average reduction: 79% 0 AZT, 100mg AZT 300mg ddC, 0.75mg ddI, 100mg d4T, 40mg 3TC, 150mg
Source: UNAIDS, Brazilian Department og Healthvi,vii 3. Current cost of treatment regimens

Example 1: sexually transmitted diseases

Treatment of gonorrhea with ciprofloxacin, indicated when there is resistance to first-line
antibiotics, is not very expensive on an individual basis because it is administered in a single
dose (500mg/adult). Nonetheless, when only the originator's brand drug is available,
treatment can be eight times more expensive than in countries where Bayer does not have a
monopoly. For example, in South Africa the public tender cost of Ciproxin® (Bayer's
ciprofloxacin, 2 x 250mg tablet) in 1999 was US$ 0.8 as compared with US$ 0.1 (2x250mg
tablet) in Guatemala, where non-proprietary ciprofloxacin was acquired in the 2000 public
tender from a well-known alternative manufacturer (Ranbaxy).
Example 2: Cryptococcal meningitis secondary prophylaxis (fluconazole 200 mg daily)

Nowadays, it costs an HIV/AIDS patient living in Thailand US$9 per month to prevent
cryptococcal meningitis, a life-threatening disease. But if this person happens to be in South
Africa, he/she will pay US$123 per month for the same product supplied by the public sector
(nearly 14 times more). To purchase this same drug from the private sector would cost 71.4
times more.
Example 3: antiretroviral therapy using a combination of ddI 400 mg + d4T 80 mg daily

In Brazil, where these two antiretrovirals are produced locally as generics, the total monthly
cost of dual therapy combination is the cheapest at US$78 per month, followed by Thailand,
where both products are also available locally as generics, at US$96 per month. In Uganda,
where no generics are available, the total cost comes to US$342 per month, that is 4.4 times
more than in Brazil, and 3.5 times more than in Thailand.
In other words, it costs the Brazilian public health system the same amount to treat 1,000
people living with HIV/AIDS per month as it does the Ugandan government to treat 228
people living with HIV/AIDS per month (excluding the cost of diagnostics and other
Example 4: AZT/3TC 600/300 mg + NVP 400 mg daily

In Brazil, the AZT/3TC combination is produced locally (NVP will be produced by the end of
this yea cost of triple therapy is around US$192, while in Thailand, where
none of these are available as generics, the total cost comes to US$348 (1.8 times more
In other words, it costs the Brazilian public health system the same amount to treat 1,000
people living with HIV/AIDS as it does the Thai government to treat 552 people living with
HIV/AIDS (excluding the cost of diagnostics and other expenses).
The availability of cheaper drugs had enabled the Brazilian Government to provide
antiretrovirals to more than 80,000 citizens by the end of 1999, which led to a more than 50%
drop in AIDS-related mortality between 1996 and 1999.n 1997 there were 580,000 people
living with HIV/AIDS in Brazil.n this middle-income country, this allowed the
government to save more than US$472 million on hospitalisations and treatment for
opportunistic infectiThis demonstrates that when ARVs are
available at affordable levels, in addition to the high social cost of not providing them there
are real financial costs. It can become more expensive for a government not to offer ARVs
than to provide them, because of the high cost associated with caring for people with AIDS.
4. Previous international procurement initiatives
Similar price differentials have been recorded in other areas. For example, through concerted international efforts, prices of vaccines essential for the prevention of infectious diseases, which constitute a huge burden on developing countries, were brought down without affecting quality (table 3). A further example is that of contraceptives (table 4). Table 3: Comparison of 1999 vaccine prices per paediatric dose
US domestic vs PAHO Prices
Measles Recombinant Hib
(Oral Polio
Hepatitis B (10-dose
(1-dose vials) vials)
US private sector (catalogue) price/dose* (1-dose vials) US government (CDC) price differential: US private vs public sector PAHO price per dose price differential: US government vs Source: PAHO (Pan-American Health Organization), WHO - 1999 Table 4: Comparison of 2000 contraceptives prices US domestic vs UNFPA prices
Oral contraceptives Injectable contraceptives
0.14-0.23 per cycle price differential US retail Source: UNFPA, 2000 PUBLIC INVOLVEMENT IN RESEARCH AND DEVELOPMENT
Pharmaceutical companies claim that high prices are necessary to fund research and development, yet the data presented confirms that for five of the six ARVs analysed (see annexes 4, 7, 8, 9 and 10), public funding played a significant role in drug discovery and/or clinical research. The Pharmaceutical Research and Manufacturers of America (PhRMA), an industry group, estimate that private industry finances 43% of drug development.important role played by national governments is evidenced by the fact that patents for important AIDS drugs are in the hands of the US government. This is the case for two drugs covered in this report: didanosine and stavudine (annexe 4 and annexe 9 respectively). Besides research and development, long time-to-approval is another justification for high prices cited by industry. However, antiretrovirals have the shortest time-to-approval of any class of drugs: a mean of 44.6 months, half the industry average of 87.4 months.clinical trials for these drugs is further reduced by heavy government sponsorship: more than a third of patients enrolled in US trials participated in trials funded by the US government. Whatever the true investment of the pharmaceutical industry in researching and developing antiretrovirals, these drugs have earned the companies consistent revenue. Between 1997 and 1999, Glaxo Wellcome's sales for AZT, 3TC, and Combivir® (a one-pill combination of AZT and 3TC) totalled more than US$3.8 billion. Bristol-Myers Squibb sold more than US$2 billion worth of d4T and ddI over the same period. E. DISCUSSION

Currently there are approximately 32.3 million cases of HIV/AIDS in developing countries
(95% of global estimate of 34.3 million). More than 2.5 million people die each year from the
disease. The introduction of antiretrovirals has dramatically reduced mortality in wealthy
countries, but the course of the disease has not been significantly altered in poor countries.
There are diverse factors that affect access to medicines: quality of diagnosis, accurate
prescribing, selection, distribution and dispensing of medicines. But one of the most
significant barriers to access is the price of drugs. Currently, in most poor countries the prices
of HIV drugs condemn people with AIDS to premature death.
This report compares a wide range of prices of brand name and generic drugs both between
and within countries. The widely divergent prices for the 10 selected products put into
question current pricing practices and highlight the lack of transparency with regard to the
relationship between production costs and prices.
A series of factors influence prices:
1) Monopoly rights. When multinational drug companies have exclusive marketing
rights, they tend to demand maximum possible prices, catering to country elites and leaving their drugs out of reach of the vast majority of people living in developing countries. There are no links between prices and public health needs or buying power. 2) Generic production. The presence or absence of generic competition in the market is
a key determinant of pricing levels. Competition brings down prices dramatically. The example of Brazil is the most striking in the report. However, there are some exceptions, data also point to situations (such as with fluconazole in Thailand) in which multinational companies sometimes choose to sell patented products at a steep premium, even when they are faced with aggressive, low-priced competitors. 3) Price/cost disconnect. The ability of generic manufacturers to charge extremely low
prices shows that prices of branded products bear no relation to production costs. From the data, we see that generic manufacturers, which must turn a profit to survive, are able to sell medicines at a fraction of the price of branded products. In order for developing country governments to address their acute AIDS crises, it seems appropriate to attempt to facilitate access to low-cost, quality generic production. As they are now, research and development costs should be borne by wealthy countries. 4) Internationally co-ordinated programs. The report includes historical data from
vaccine and contraceptive procurement models in an effort to demonstrate what is possible when international organisations, national governments and pharmaceutical companies work together to meet priority health concerns (oral contraceptive prices are 130-240 times cheaper in poor countries than in the US). Is the current UNAIDS initiative with five pharmaceutical companies to reduce prices by five times a response of adequate magnitude to the current pandemic? Mechanisms to reduces the cost of HIV/AIDS treatment: 1) Role of generics. The most recent patent of all products in this report was granted for
efavirenz on 17 August 1992, before many developing countries put their patent systems into effect. This means that practically speaking, generic versions of all of these products could be made available today in a significant number of developing countries; countries only need to identify quality affordable suppliers and register these products with regulatory authorities. However, patent status is a national issue and needs to be researched on a country-by-country basis. 2) Intellectual property rights: public health safeguards. Since the creation of the
World Trade Organization (WTO) in 1994, and the completion of the Trade Related Aspects of Intellectual Property Rights (TRIPS) Agreement, more and more countries (WTO had 137 member states as of 14 June 2000xiiare obligated to grant 20 year patent protection for drugs. According to the TRIPS agreement, this minimum standard must be enshrined in national law by 2006 in all signatory countries. Developing countries had a deadline of January 2000, with some exceptions, while least developed countries have until 2006 to change national laws. In practical terms this means that poor countries will soon lose access to affordable life-saving medicines unless they write TRIPS safeguard provisions into their national laws. Three safeguards are paramount: One element of TRIPS that is designed to mitigate the negative consequences of
granting monopoly rights is compulsory licensing (article 31). According to this
article, WTO member states may allow the use of a patent by a third party without the
owner's consent. There are no limitations within TRIPS regarding the grounds for
issuing a compulsory license, only conditions to be fulfilled. For instance, a potential
user must make efforts to obtain a license on reasonable commercial terms before a
government can issue a compulsory license. However, even this condition can be
waived "in cases of national emergency, other circumstances of extreme urgency,
public non-commercial use (…)".xiii In any case where compulsory licenses are
granted for medicines, all normal safety, quality and efficacy standards would be
A second critical safeguard is parallel imports, which is based on the principle of
exhaustion of rights (TRIPS article 6). When enshrined in national law, this allows
cross border trade in a patented product without the manufacturer's permission.
Parallel imports allow countries to import brand name products from countries where
they are sold by the patent holder or licensee at lower prices.
Finally, national laws should include "Bolar" provisions. This allows generic
manufacturers to begin preparing generic production and completing regulatory
procedures before patents expire so that upon expiration they can immediately begin
selling their products. This provision means that less expensive generic products can
be available much more rapidly after patents expire.


1. Governments from both developed and developing countries, WHO, UNAIDS, NGOs, with the input of both proprietary and generic pharmaceutical companies, should work together to find sustainable solutions for countries that do not have adequate access to life-saving and other key medicines. 2. International comparative price studies should be carried out by international organisations such as WHO or UNAIDS on an ongoing basis to give developing countries the tools to spend their health budgets more effectively. They should include both raw material and finished product prices, taking into account internationally recognised quality standards. The UN agencies were given a mandate to undertake this activity in a WHA resolution that was adopted in May 2000.xiv 3. Least-developed countries should take advantage of the transitional period allowed within the WTO agreements. They are not obligated to change their national laws to be compliant with TRIPS until 2006. When new laws are drafted, ministries of health should be involved in the process, and should seek advice and counsel from United Nations specialised agencies including WHO, which has a mandate to provide technical assistance on this issue. 4. In countries in which patent protection presents a barrier to access to medicines, international organisations should actively support countries' efforts to improve access. This can be achieved through the following means: Þ the government, or an individual or organisation can request a voluntary
license. This will allow life-saving drugs to be supplied by the generic industry
(through imports or by local production), and will bring prices down;
Þ if a voluntary license cannot be obtained then a compulsory license can be
granted by national governments; Þ also, if a required drug is patented in the country, and it is sold in other countries by the same company at a lower price, parallel importing from a
second country is an option to be considered.
5. UN organisations (WHO or UNAIDS) should support national governments by beginning international procurement of AIDS drugs. They should immediately put out tenders to the proprietary and generic industry for mass procurement of opportunistic infection and anti-HIV medicines. National governments would then be able to access low cost medicines to support their national AIDS programmes. The UN should use previous vaccine and contraception procurement projects as a guide. 6. Technology transfer should be supported by international organisations and national governments as a way to guarantee a sustainable production of affordable medicines. For those countries with considerable production experience, the goal should be to begin producing primary materials in addition to formulating products. 7. According to initial information, the five company/UNAIDS initiative would reduce antiretroviral prices byxv the cost of antiretrovirals down to US$2,250 per year, per patient. This sum is still far too expensive for the vast majority of people living in developing countries. However, generic manufacturers in Brazil and Thailand are confident of their ability to produce antiretrovirals that would result in a yearly triple combination price of US$200. This cost level will make it possible for developed countries, international organisations and donor agencies to contribute significantly to increasing access to combination therapy, and for developing countries to make allocations within their national budgets. CONCLUSION
While antiretroviral treatment has reduced AIDS-related mortality by over 70% in developed countries, these revolutionary therapies have been denied to people in developing countries. Unless these treatments are made more widely available, HIV/AIDS will continue cutting a broad swath through many developing countries. If the price of combination therapy were reduced to US$200 a year, millions of people would have access to drugs that can prolong their lives. This is feasible according to information from generic producers and historical experiences from vaccine and contraceptive initiatives. Although there are additional costs associated with treating people with HIV/AIDS, price reductions of this scale would allow developing countries, in partnership with developed countries, international organisations and donors, to tackle the problem of providing care for people with HIV/AIDS. The means to accomplish this are available. What is needed is the political will to mobilise resources on a global scale to combat this pandemic. As an organisation that cares for people with AIDS, MSF believes that the time has come to respond to the ethical imperative to provide treatment to people who are in need. i Report on the global HIV/AIDS epidemic, UNAIDS, June, 27, 2000 ii Hirschel B. & Francioli, P. Progress and problems in the fight against AIDS, New England Journal of Medicine, 3338, 906-908. 1998 iii Human development report 2000: human rights and human development, UNDP, 29 June 2000. iv WHO Model List of Essential Drugs December 1999 : v K. Myhr, Pharmaceutical pricing: Law of the jungle, K. Myhr, June 2000 (unpublished) vi B.Sam, UNAIDS, quoted in WHO-Health Technology and Pharmaceuticals, Revised Drug Strategy, vii Unpublished data from the Brazilian Department of Health. viii Human development report 2000: human rights and human development, UNDP, 29 June 2000. ix PhRMA, 2000 Industry Profile, p. 23. Available at Hhttp://www.phrma.orgH. x Kaitin, K & Healy E. The new drug approvals of 1996, 1997, and 1998: drug development trends in the user fee era, Drug Information Journal, Vol. 34, pp. 1–14, 2000. xii xiii Velasquez G. & Boulet P. Globalization and Access to drugs. Perspectives on the WTO/TRIPS Agreement, Health Economics and Drugs DAP series n° 7. Revised. Geneva, Switzerland, WHO 1999. xiv HIV/AIDS: confronting the epidemic, WHA53.14, Resolution of the World Health xv This calculation is based on the often-cited US$ 15,000 price for a three drug antiretroviral combination.


Biochem. J. (2012) 443, 549–559 (Printed in Great Britain) First identification of small-molecule inhibitors of Pontin by combiningvirtual screening and enzymatic assay Judith ELKAIM*, Michel CASTROVIEJO†, Driss BENNANI*, Said TAOUJI‡, Nathalie ALLAIN‡, Michel LAGUERRE*,Jean ROSENBAUM‡, Jean and Patrick LESTIENNE*Molecular Modeling Group, IECB-CNRS-Universit´e de Bordeaux, UMR 5248, 2 rue R. Escarpit, F-33607 Pessac, France, †Platform Protein Expression and Purification, CNRS, UMR5234, 146 rue L. Saignat, F-33076 Bordeaux Cedex, France, and ‡Physiopathologie du Cancer du Foie, INSERM U1053-Universit´e de Bordeaux, 146 rue L. Saignat, F-33076 BordeauxCedex, France

HIGHLIGHTS OF PRESCRIBING INFORMATION Suicidal Behavior and Ideation (5.1) These highlights do not include all the information needed to use Patients should be advised that VIMPAT may cause dizziness VIMPAT® safely and effectively. See full prescribing information and ataxia. (5.2) for VIMPAT.