UNTANGLING THE WEB OF ANTIRETROVIRAL PRICE REDUCTIONS

18th Edition – July 2016

www.msfaccess.org PREFACE In this report, we provide an update on the key facets of HIV treatment access. It includes the latest HIV treatment guidelines from World Health Organization (WHO), an overview on pricing for first-line, second-line, and salvage regimens, and a summary of the opportunities for – and threats to – expanding access to affordable antiretroviral therapy (ART). There is a table with information on ARVs, including quality assurance, manufacturers and pricing on pages 19 to 21.

Detailed information on key antiretroviral drugs and fixed-dose combinations is available at:

www.msfaccess.org/utw2016

THE MSF ACCESS CAMPAIGN In 1999, on the heels of Médecins Sans Frontières (MSF) being awarded the Nobel Peace Prize – and largely in response to the inequalities surrounding access to HIV/AIDS treatment between rich and poor countries – MSF launched the Campaign for Access to Essential Medicines. Its sole purpose has been to push for access to, and the development of, life-saving and life-prolonging medicines, diagnostics and vaccines for patients in MSF programmes and beyond.

www.msfaccess.org

MSF AND HIV Médecins Sans Frontières (MSF) began providing antiretroviral therapy to a small number of people living with HIV/AIDS in 2000 in projects in Thailand, South Africa and Cameroon. At the time, treatment for one person for one year cost more than US$10,000. With increased availability of low-cost, quality antiretroviral drugs (ARVs), MSF provides antiretroviral treatment to 247,000 people in 18 countries, implements treatment strategies to reach more people earlier in their disease progression, and places people living with HIV at the centre of their care.

Over the past 16 years, the MSF Access Campaign has been monitoring the barriers to availability and affordability of life-saving ARVs and appropriate formulations, including patent monopolies, prices and lack of generic competition through Untangling the Web and pushing for the uptake of policies that promote access to affordable quality medicines. Due primarily to generic competition, the price of ARVs has dropped by more than 99% over the last 15 years, but the price of the newest drugs, already needed by some people in MSF projects, is prohibitive and a source of great concern both for MSF and national treatment programmes.

PATENT OPPOSITION DATABASE The Patent Opposition Database was launched by the MSF Access Campaign in October 2012 as an online space where civil society can share the resources and tools needed to oppose patents on medicines. The database gathers contributions from around the world. It allows documents to be shared, arguments to be replicated, and new alliances to be forged, with the aim of successfully opposing patents and ultimately improving access to medicines in developing countries. To find out more about patents that block access to essential medicines and what you can do to challenge them, or to contribute by sharing resources, visit: www.patentoppositions.org

Médecins Sans Frontières | July 2016 TABLE OF CONTENTS TABLE OF CONTENTS

2 STATE OF HIV TREATMENT ACCESS Speed up treatment scale-up in Western and Central Africa

4 OPTIMISING HIV TREATMENT

7 PRICING High antiretroviral prices in middle- and high-income countries

11 REGISTRATION Lack of access to dolutegravir in India

12 PATENT OPPOSITIONS AND PATENT LAW REFORM Patent oppositions for hepatitis C Evergreening

14 TRADE AGREEMENTS LDC exemption from pharmaceutical IP extended Colombia: Compulsory licence threat invites US pressure

16 STOCKOUTS Market shaping institutions – what needs to happen Update on the Medicines Patent Pool’s new licences

18 CONCLUSION

19 ANNEX: SUMMARY TABLE OF ALL PRICES

22 REFERENCES

24 GLOSSARY AND ABBREVIATIONS

Untangling the Web of ARV Price Reductions | msfaccess.org/utw2016 1 STATE OF HIV TREATMENT ACCESS

In 2000, when the International AIDS Conference was last held in Durban, South Africa, a basic antiretroviral (ARV) regimen cost over US$10,000 per person per year (pppy), multilateral programmes funding the fight against HIV, TB, and malaria did not exist, and many donors – such as the US government – had yet to provide a single dollar for antiretroviral treatment in resource-limited countries.

Now, in 2016, 17 million HIV-positive for 2020, referred to as ‘90-90-90’.3 people are receiving lifesaving To meet these targets, the number of THE 2020 UNAIDS antiretroviral therapy (ART),1 and the people on treatment will need to more

STATE OF HIV TREATMENT ACCESS ACCESS OF HIV TREATMENT STATE TARGET: 90-90-90 lowest price for a generic, World Health than double again, since nearly 20 Organization (WHO)-recommended million HIV-positive people are newly By 2020, 90% of all first-line regimen is $100 pppy. eligible for ART under the new ‘treat- HIV-positive people will be all’ recommendation.1 aware of their status; 90% In 2015, the number of people starting HIV treatment surpassed the number At the UN High Level Meeting on of all people diagnosed of new infections in Africa for the HIV in June 2016, governments with HIV will have access to first time. Since 2010, the number of agreed on a global target: reaching sustained ART; and 90% of people receiving ART has more than 30 million people with treatment people on ART – or 73% of doubled.1,2 The push to continue by 2020. Reaching this goal will all HIV-positive people – will ARV scale-up has gained momentum require increased and sustained achieve viral suppression.3 around the UNAIDS global targets support from donors. © Isabel Corthier

Tsandia receives her antiretroviral medicines at the HIV department of the Arua Regional hospital in Uganda.

2 Médecins Sans Frontières | July 2016 STATE OF HIV TREATMENT ACCESS GRAPH 1: GENERIC COMPETITION AS A CATALYST FOR PRICE REDUCTION FOR A FIRST-LINE REGIMEN

riinator roducts eneric roducts 12000

13 10000

8000

6000

4000

US$ per person year 2 2000

0 132 June 00 Sept 01 June 02 June 03 Dec 03 Apr 04 June 05 June 06

Since 2000, MSF has been providing HIV care and treatment to people in developing countries. Today, MSF provides HIV treatment for nearly 250,000 people.

SPEED UP TREATMENT SCALE-UP IN WESTERN AND CENTRAL AFRICA

Although HIV prevalence is lower in worsened by the Ebola outbreak - tests, drug stockouts, out-of-pocket Western and Central Africa than in add to barriers that include limited fees for healthcare, and lack of Southern Africa, over a quarter of access to diagnostic and monitoring decentralised treatment.4 all AIDS-related deaths occur in the region, including 40% of all deaths among children.4

In Central African Republic, HIV prevalence is 5%, but HIV accounts for 84% of hospital-based deaths where MSF works. In Democratic Republic of the Congo, three out of four HIV-positive people who present to the hospital where MSF works are too sick to save.

In 2015, only 1.8 million people (28%) of the region’s

6.5 million HIV-positive people Sam Phelps

were accessing ART.1 Political © instability, inadequate funding and Mohamed (left) is tested for HIV at an MSF mobile clinic in Conakry, Guinea. weak healthcare systems - some

Untangling the Web of ARV Price Reductions | msfaccess.org/utw2016 3 OPTIMISING HIV TREATMENT

COUNTRIES SHOULD IMPLEMENT WHO GUIDELINES

Immediate treatment and a steady WHO has recommended immediate of care that put the patient at the supply of affordable medicines are and lifelong ART for everyone with centre of their treatment.10 essential to curbing the HIV epidemic. HIV: all infants, children, adolescents, Countries should implement the WHO ART lowers the risk of serious illness and adults, including pregnant and recommendations, including ‘test and and death, reduces the risk of breastfeeding women, regardless of start’, routine viral load monitoring developing tuberculosis (TB) by CD4 cell count or disease stage.9 [see below], better drugs (new 65%, and reduces HIV transmission In June 2016, WHO issued new HIV ARVs and once-daily, fixed-dose OPTIMISING HIV TREATMENT OPTIMISING HIV TREATMENT by 96%.5,6,7,8 treatment guidelines, including combinations), adherence support, and In light of the individual and recommendations for new ARV differentiated models of care to facilitate community benefits of HIV treatment, regimens and differentiated models rapid scale-up and quality patient care.10

ROUTINE VIRAL LOAD MONITORING

Access to viral load testing – the gold standard for HIV treatment monitoring – is essential to achieving the 90-90-90 targets. For infants, an early diagnosis can be life-saving – and requires viral load testing. In 2016, WHO recommended point-of-care viral load testing for HIV-exposed infants.10

Since 2013, WHO has recommended routine viral load monitoring for diagnosing HIV treatment failure; the 2015 guidelines recommend viral load monitoring – now with dried blood spot testing – at six and 12 months after starting ART. For stable patients, viral load monitoring is recommended once every year thereafter instead of CD4 cell count monitoring.9,10

As tests have become more affordable and rollout less complex, more countries have adopted routine viral load as part of national policy. However, implementation still lags far behind; a 2014 WHO study of 122 low- and middle-income countries found that only 22% of people on ART received viral load monitoring.11

MSF began implementing viral load testing in 2012. In Lesotho, Malawi, Mozambique, Swaziland, Uganda, and Zimbabwe, risk factors for having a detectable viral load have been identified, leading to interventions including a child-friendly clinic, community ART groups, and enhanced adherence counselling. Routine viral

load testing has triggered a switch to © Isabel Corthier second-line treatment and enhanced adherence counselling in 10% to 68% People wait to have their blood tested to measure their viral load at the HIV department of Arua Regional Hospital in Uganda. of patients. 12

4 Médecins Sans Frontières | July 2016 OPTIMISING HIV TREATMENT

IMPROVING FIRST-LINE TREATMENT

The 2015 WHO HIV treatment guidelines added recommendations for two alternative first-line ARVs: dolutegravir (DTG), a well-tolerated integrase inhibitor that rapidly lowers HIV viral load and is robust, with very few documented cases of resistance,13 and a lower, equally effective dose of efavirenz (EFV; 400mg vs. 600mg)9 that is better tolerated than the higher dose.14 Before these ARVs become part of a preferred first-line regimen, additional clinical data on their safety

© Ron Haviv/VII Photo and efficacy during TB treatment, pregnancy, and breast-feeding are An MSF outreach worker measures out antiretroviral medication during a home visit needed;9,15 these studies are planned in Dawei, in southeastern Myanmar. or underway.

BETTER SECOND-LINE TREATMENT

As access to viral load monitoring increases, more people in need of second-line treatment will be identified. The WHO treatment guidelines have added two alternative recommendations for second-line ART: a heat-stable, fixed-dose combination (FDC) of darunavir/ritonavir (DRV/r) and a two-drug regimen of raltegravir (RAL; an integrase inhibitor) with lopinavir/ritonavir (LPV/r).10

DRV is a boosted protease inhibitor (PI) with fewer side effects than the other second-line protease inhibitors (although it cannot be used during 16,17,18

rifampicin-based TB treatment). © Julie Remy But access to DRV/r is limited; there is no quality-assured heat-stable Loved Mupandanana is HIV positive, and her first-line treatment for HIV seems to be FDC on the market, and the current failing. At Gombe clinic, in Manicaland Province in Zimbabwe, she is receiving counselling about the need to move on to second-line treatment. price of generic DRV alone is at least three times more than other protease inhibitors, making it costly for wide- spread use. In 2015, MSF provided second-line HIV treatment for 10,200 people.

Continued overleaf

Untangling the Web of ARV Price Reductions | msfaccess.org/utw2016 5 Optimising HIV treatment continued

THE ARV PIPELINE FOR ADULTS

The ARV pipeline includes new drug three TAF-based FDCs (in November improve adherence and significantly formulations and classes. Tenofovir 2015, March 2016 and April 2016). reduce the cost of HIV treatment; alafenamide (TAF), a new prodrug of Stand-alone TAF has been approved interim results from a trial of a long- tenofovir disoproxil fumarate (TDF), in Europe (and filed in the US) for acting injectable combination (rilpivirine is equally effective as the currently hepatitis B treatment only. If Gilead, and cabotegravir) are promising, available version, at one-tenth of the the company marketing TAF, does not although an interaction between dose. TAF is likely to be safer, and register the drug as a single ARV for cabotegravir and rifampicin requires should be significantly less expensive use in HIV, generic manufacturers may further study.20,21,22,23 19

OPTIMISING HIV TREATMENT OPTIMISING HIV TREATMENT to produce than TDF, but data on face complications and long delays New ARV classes include attachment drug interactions between TAF and TB in registering TAF-containing FDCs in and maturation inhibitors; there are also treatment are needed. other countries. new versions of integrase inhibitors and The United States Food and Drug Long-acting, injectable ARVs with non-nucleoside reverse transcriptase Administration (USFDA) has approved monthly or bi-monthly dosing could inhibitors (NNRTI) in development.

THE ARV PIPELINE FOR CHILDREN

Only 49% of the world’s HIV-positive children difficult. The price of the pellets children had access to treatment in needs to be reduced so it is at least In 2015, MSF 2015.24 Without treatment, over half on par with the syrup, to encourage supported of all HIV-positive children die before countries to adopt them. their second birthday;25 treating infants treatment for The Drugs for Neglected Diseases when they are less than 12 weeks old 6,800 HIV-positive initiative (DNDi) LIVING study is lowers mortality by 75%.26 looking at the safety, effectiveness pregnant women, Research and development of and acceptability of LPV/r pellet-based and post-exposure paediatric ARVs and FDCs has lagged therapy in infants (>four weeks old) treatment for far behind adult treatment, which has and children, with enrolment having 4,400 babies. severely limited treatment options for begun in Kenya.30 HIV-positive infants and children.

There is a new pellet formulation of LPV/r, which is part of the WHO- recommended first-line regimen for children under three years old.10 In May 2015, the USFDA granted tentative approval for LPV/r pellets for children who weigh >5 kg and are over 14 days old.27,28 This formulation of LPV/r is available to a limited group of low- and middle-income countries through a Medicines Patent Pool (MPP) voluntary licence (VL), although one year after stringent regulatory authority (SRA) approval, it has not yet been made commercially available.

Pellets could replace LPV/r syrup, which

contains 40% alcohol and propylene © Sydelle WIllow Smith glycol, requires refrigeration, and has been described as tasting “horrible”29 – Jennipher Mwamvera is a mother of four and a patient in the prevention-of-mother-to- child transmission of HIV (PMTCT) program in Thyolo, Malawi. all of which have made treating young

6 Médecins Sans Frontières | July 2016 PRICING PRICING

Affordable generic ARVs have made HIV treatment scale-up possible in countries that can access them. Robust competition between multiple generics producers has dramatically lowered the price of first-line antiretroviral therapy over the last decade-and-a-half.

FIRST-LINE REGIMENS Since 2014, there has been a 30% (TDF/FTC/EFV) can be as low as Aurobindo’s generic version of reduction in the price for generic $100 pppy, down from $143 pppy in dolutegravir will have a price of first-line treatment.* If countries are 2014. Prices for first-line treatment $44 pppy,32 which is on par with able to import and use generics, are unlikely to decrease further, since the price of efavirenz 600mg. the price for the fixed-dose of the they are now close to the minimum A fixed-dose combination of DTG WHO-recommended combination sustainable production price, with TDF/XTC should be available of tenofovir/emtricitabine/efavirenz according to experts.31 by the end of 2017.

Continued overleaf

GRAPH 2: THE PRICES OF DIFFERENT FIRST-LINE REGIMENS TODAY

1200 133

1000

800 13 600

400 US$ per person year

200 1 1 12 1

0 Lowest Lowest Lowest Lowest Lowest Lowest Originator Originator generic price generic price generic price generic price generic price generic price price for price for AZT/3TC/NVP TDF/3TC + NVP AZT/3TC + EFV TDF/3TC + EFV TDF/3TC/EFV TDF/FTC/EFV Cat.1 Cat.2 TDF/FTC/EFV TDF/FTC/EFV

* Price reductions may be due in part to currency fluctuations.

Untangling the Web of ARV Price Reductions | msfaccess.org/utw2016 7 Pricing continued

GRAPH 3: THE EVOLUTION IN PRICE OF DIFFERENT FIRST-LINE REGIMENS PRICING

FFF 1 illonce a day FF 1 illonce a day F 1 illtice a day 1 illonce a day

600

500

2 400 1

300

200 1 US$ per person year 1 100 1

0 June 07 June 08 Dec 09 June 10 June 11 June 12 June 13 June 14 June 16

HIGH ANTIRETROVIRAL PRICES IN MIDDLE- AND HIGH-INCOME COUNTRIES

According to UNAIDS, 70% of all not included in voluntary licensing High-income countries such as the HIV-positive people will be living in agreements, and/or have not used US are struggling with spiralling middle-income countries by 2020.33 TRIPS flexibilities such as compulsory costs of patented medicines, including ARVs. In the US, the Several ARVs are still on patent in licences.* Instead, they must pay combination of TDF/FTC/EFV (sold middle-income countries. Some high prices to originator companies under the brand name Atripla) costs lower- and upper-middle-income for patented drugs on a case-by- nearly $30,000 pppy35 versus $100 countries where patent barriers on case basis or under ‘tiered pricing’ pppy for Indian generic versions. key ARVs remain cannot produce or schemes that are not based on a buy generic ARVs, because they are realistic concept of affordability.34

* The World Trade Organization’s Trade-Related Aspects of Intellectual Property (TRIPS) Agreement can and should be interpreted in light of the goal “to promote access to medicines”. Legal safeguards include (but are not limited to) enabling networks of people living with HIV/AIDS to challenge patent claims before and/or after they are granted; the right to examine patent claims strictly and reject new use and/or new forms of known medicines; the right to register generic versions of patented medicines; the right to issue compulsory licences (CLs; these allow countries to import or locally produce generic versions of patented medicines without the patent holder’s consent); and the right to import and resell lower-priced medicines from other countries instead of paying higher prices for them – also without consent from the patent holder (called parallel importing).

8 Médecins Sans Frontières | July 2016 PRICING

SECOND-LINE REGIMENS

Boosted protease inhibitors are the Although LPV/r must be taken twice Prices for boosted protease inhibitors backbone of second-line regimens. a day, it can be dose-adjusted for use are especially high in middle-income The lowest-priced generic second- with rifampicin-based TB treatment. countries, since many of them have line regimen, zidovudine/lamivudine LPV/r is still more expensive than patent barriers and are excluded from (AZT/3TC) and atazanavir/r (ATV/r), is ATV/r, at $243 pppy versus $213 voluntary licensing agreements. In now priced at $286 pppy. Since 2014, its designated Category 2 countries,* pppy [see graph 4]. The price of the price has dropped by 11%, from AbbVie charges higher prices for LPV/r generic LPV/r is 5% higher than $322 pppy. than in least-developed countries the originator product, because the (LDCs): $740 pppy (which has not Switching to second-line therapy originator company, AbbVie, has been changed since 2012), compared to nearly triples the price of treatment consistently undercutting generic $231 pppy in LDCs [see graph 4]. In [see graph 5]. Currently, there competition with slightly lower prices. Malaysia, prices for LPV/r were quoted are two WHO-preferred boosted above $3,500 pppy in 2014.36 The For several of the newer second-line protease inhibitors for second- originator price from Bristol-Myers options, current demand is low. The line regimens, ATV/r and LPV/r; Squibb (BMS) for atazanavir– which one alternative boosted protease price of generic versions has not yet must be used with ritonavir (RTV) – is inhibitor, darunavir+r (DRV+r); and come down, and only a few $816 pppy; AbbVie’s originator price an alternative, twice-daily two-ARV producers have entered the market. for RTV is set on a “case-by-case” basis. regimen, the integrase inhibitor DRV is much more expensive than The lowest originator price for RAL is raltegravir (RAL) plus LPV/r.10 ATV/r or LVP/r, and it is not available $675 pppy; the lowest-price generic as a fixed-dose combination with A generic, fixed-dose, heat-stable version is $973 pppy [see graph 6]. ritonavir (RTV or r). Darunavir is formulation of ATV/r is available. It has Currently, RAL is taken twice daily, available from the originator for fewer side effects than LPV/r, although however, Merck plans to submit it cannot be used during rifampicin- $663 pppy; generic versions are data to the USFDA and the European based TB treatment. Because of supply $1217 pppy, since the current low Medicines Agency (EMA) to seek problems with LPV/r, an increase demand prevents companies from approval for once-daily RAL.37 RAL in demand for ATV/r is expected, being motivated to commercialise it can be dose-adjusted for use during hopefully leading to lower prices. in low- and middle-income countries. rifampicin-based TB treatment.38

GRAPH 4: THE EVOLUTION IN PRICE OF BOOSTED PROTEASE INHIBITORS FOR SECOND-LINE REGIMENS

oest eneric r riinator rice or at 1 r oest eneric r riinator rice or at 2 r

1200

13 1000 1

800

600 400 23 US$ per person year 3 231 200 213

0 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

* Albania, Armenia, Azerbaijan, Belarus, Bolivia, Bosnia and Herzegovina, China, Colombia, Dominican Republic, Ecuador, El Salvador, Fiji, Georgia, Guatemala, Guyana, Honduras, India, Indonesia, Jamaica, Jordan, Kazakhstan, Kyrgyzstan, Macedonia, Marshall Islands, Micronesia, Moldova, Mongolia, Montenegro, Nicaragua, Pakistan, Papua New Guinea, Paraguay, Peru, Philippines, Serbia, Sri Lanka, Suriname, Syria, Tajikistan, Thailand, Tonga, Turkmenistan, Ukraine, Uzbekistan, Viet Nam.

Continued overleaf

Untangling the Web of ARV Price Reductions | msfaccess.org/utw2016 9 Pricing continued

SALVAGE REGIMENS PRICING

There is an urgent need for more + ETV), in countries that fall into the $1,217; this does not include the ritonavir affordable third-line, or salvage regimens select group eligible for access pricing it must be used with. At the same time, for people that have acquired resistance from originators (but many countries the access price from the originator has to first- and second-line treatment. are paying much more). This represents dropped by 17%, from $810 to $675. Low volume and high prices from both nearly an 18-fold increase over the lowest A quality-assured generic RAL is priced at originator and generic companies keep first-line prices, and nearly a seven-fold $973 pppy, but it is still more expensive increase over the most affordable these medicines out of reach. than the originator version, which has second-line regimen [see graph 5]. The lowest price for a salvage regimen stayed at $675 since 2011. The originator today is $1,859 pppy, for darunavir+r, Since 2014, the price of generic DRV price for ETV has stayed at $438 since raltegravir and etravirine (DRV+ r + RAL has increased by 10%, from $1,095 to 2011 [see graph 6].

GRAPH 5: PRICE COMPARISONS OF FIRST-LINE, SECOND-LINE AND POSSIBLE THIRD-LINE TREATMENT REGIMENS

2000

1, 1500 x 1. x .

1000

x 2.

500 US$ per person year 1 2 0 Lowest generic price Lowest generic price RAL+DRV+r+ETV TDF/3TC/EFV AZT/3TC+ATV/r First-line regimen Second-line regimen Third-line regimen

GRAPH 6: PRICES FOR THIRD-LINE ARVS

600 oriinator rice 00 oriinator rice 600 eneric rice 00 eneric rice 100 oriinator rice 2000

1750 12

1500

1250 121 1 1000 13 3 1 750 3 500

US$ per person year 3 250

0 June 11 June 12 June 13 June 14 June 15 June 16

10 Médecins Sans Frontières | July 2016 REGISTRATION REGISTRATION

In many countries, marketing authorisation for promising new ARVs can take several years; this type of regulatory lag forces people living with HIV/AIDS to wait for life-saving medicines. National Drug Regulatory Authorities (NDRAs) do not always have the resources to ensure timely registration of more affordable generic versions of new ARVs, and/or fail to prioritise them.39

Pharmaceutical companies don’t Collaborative or regional registration new drugs for neglected diseases, ARVs often prioritise registration in low- processes have reduced the time to for paediatrics, and salvage regimens. and middle-income countries. Some registration for some products in In addition, the Indian NDRA should originator companies shift the some participating countries. These prioritise new ARVs, FDCs, and child- responsibility for filing registration collaborations should be considered friendly formulations, taking note of, dossiers in high-burden developing by national regulatory authorities to and relying on WHO guidelines and/or countries to generics companies that reduce the considerable workload Expression of Interest from the have signed voluntary licences. associated with reviewing registration WHO prequalification programme.* dossiers. For example, in East Africa, Another delay is the WHO In some countries, generics companies a pilot of the African Medicines prequalification programme, which has are able to register generic versions Registration Harmonisation Initiative been essential for reviewing the quality, of medicines, but in others, when has reduced the time to registration safety, and efficacy of generic ARVs that originators don’t register their ARVs by 50% in Burundi, Kenya, Rwanda, aren’t always reviewed or approved by before generics companies do, it may Uganda, and Zanzibar.39 cause significant delays, or become an a stringent regulatory authority (SRA). absolute barrier to treatment access. India’s lack of intellectual property In 2013, the median wait for WHO (IP) barriers and historically efficient prequalification was 15.1 months.39 Countries have different regulatory regulatory pathway made it possible pathways, priorities, rules, for generics companies to produce and requirements, legal frameworks, register more affordable medicines for capacities, and timelines, and some developing countries. But availability 97% of the do not have NDRAs. There is no of new quality-assured generic ARVs medicines MSF uses ‘essential documentation package’ and FDCs from India is starting to be to treat people with to streamline the registration process delayed. This is partly because India’s across all NDRAs in developing criteria to waive phase III clinical trials HIV are generics countries, and country-level are restrictive in certain cases. These made in India. bureaucracy can delay registration. criteria need to be expanded to include

BARRIERS TO UNIVERSAL ACCESS TO GENERIC DOLUTEGRAVIR FROM INDIA The pharmaceutical company ViiV has granted voluntary for registration in India. As a result, the responsibility licences (VLs) for the integrase inhibitor dolutegravir for registration is now with Indian producers that have (DTG) to several Indian generic companies through developed generic dolutegravir. They will need to do the Medicines Patent Pool (MPP). The VLs will not local clinical trials, as per the Indian NDRA requirements result in universal access to the drug, since a number of for new drugs, which will lead to a significant delay high-burden countries are excluded from the territories in the availability of affordable generics across the that can import the generic version from India. developing world. In the meantime, patients in India In India, generic DTG will only be available on the who have exhausted other treatment options are left public market or to non-governmental providers, without access to DTG, since ViiV has been dragging its leaving a number of patients with drug resistance feet to provide the medicine via compassionate use. who need immediate access without any source To ensure open generic competition in the future, from Indian pharmacies. a patent opposition for DTG has been filed in India, Although DTG has been registered in many other by and on behalf of people living with HIV, and countries, ViiV, the originator company, has not filed supported by MSF.

* These include: dolutegravir (DTG) singles and FDCs, including tenofovir/lamivudine/dolutegravir; a low-dose (400mg) efavirenz FDC and heat-stable darunavir/ritonavir Priority pediatric formulations for HIV include: lopinavir/ritonavir pellets or sachets; abacavir/lamivudine/lopinavir/ritonavir (ABC/3TC/LPV/r) zidovudine/lamivudine/lopinavir/r (AZT/3TC/LPV/r) pellets or sachets for children over three years old and lamivudine/abacavir/efavirenz (3TC/ABC/EFV 75/150/150mg) dispersible tablets for children ages 3-10 years.

Untangling the Web of ARV Price Reductions | msfaccess.org/utw2016 11 PATENT OPPOSITIONS AND PATENT LAW REFORM

INDIA, THE ‘PHARMACY OF THE DEVELOPING WORLD’, IS UNDER PRESSURE TO DROP ITS PUBLIC HEALTH SAFEGUARDS

Indian generics comprise 76% of of Intellectual Property Rights [TRIPS]). pressure – led by the multinational the ARVs used in low- and middle- India’s national patent laws include pharmaceutical lobby – to change its income countries and more than public health safeguards such as national intellectual property laws and 97% of those used by MSF in its stringent patentability criteria, and the policies, or sign free trade agreements treatment programmes.31,44 India opportunity to file legal challenges to that will dismantle them. Over the last encouraged generic competition for patents before and/or after they are two years, pharmaceutical industry- decades, since it did not introduce granted (called pre-and post-grant led pressure from the US has been patent oppositions). patents for pharmaceuticals until escalating. India must reject the 2005 (when it had to comply with India has fought off numerous demands to grant patents more easily, international trade rules under the challenges to its public health as well as TRIPS-plus rules that the World Trade Organization [WTO] safeguards, but it has been under United States is trying to force upon Agreement on Trade-related Aspects excessive external and domestic India’s Ministry of Commerce. PATENT OPPOSITIONS AND PATENT LAW REFORM REFORM LAW OPPOSITIONS AND PATENT PATENT

PATENT OPPOSITIONS FOR HEPATITIS C

Patent oppositions have been used when patent has applied for WHO prequalification for their generic claims do not meet national patentability criteria, version of the drug. and when a patent directly blocks or delays access In India, one critical sofosbuvir patent has been to essential medicines. recently granted, reversing its prior rejection in 2015. Worldwide, an estimated 150 million people This decision is now under appeal. If upheld, the have chronic hepatitis C virus infection; without patent will block additional competition from the treatment, they are at risk of developing liver Indian generics companies that do not want to sign 45 failure and liver cancer. a voluntary licence with Gilead, leaving them unable Hepatitis C can be cured with a few months’ treatment to supply sofosbuvir to millions of people in India using oral drugs, called direct-acting antivirals (DAAs). and other middle-income countries. In addition, this In 2013, the price of the first DAA on the market, decision would allow Gilead to disrupt or stop exports sofosbuvir, sent shock waves throughout the world. of the raw materials from India that are used to make Although it can be mass-produced for less than sofosbuvir’s key active pharmaceutical ingredient (API). $1 per pill,46 sofosbuvir’s launch price was $1,000 This will make it difficult for the generics companies in per pill in the US. Egypt, Bangladesh, Pakistan and Latin America that are Gilead’s patent on sofosbuvir has been opposed – producing sofosbuvir without a patent in force – and and rejected – in some countries. The patent on the without a licence agreement with Gilead – to continue pro-drug form of sofosbuvir was rejected in China and production. More patent oppositions on sofosbuvir Ukraine. In Egypt, where the primary patent application have been filed in Argentina, Brazil, Russia, Thailand, for sofosbuvir was rejected, a company called Pharco France and India.

12 Médecins Sans Frontières | July 2016 PATENT OPPOSITIONS AND PATENT LAW REFORM PATENT LAW REFORM IN BRAZIL, SOUTH AFRICA AND ARGENTINA

South Africa and Brazil are in the pharmaceutical companies involved that charge unaffordable prices. process of reforming their patent laws, in the ‘Pharmagate’ scandal (a In order to overcome IP barriers to in part to more effectively manage covert, $600,000 campaign funded generic competition, a coalition of prices for medicines, and to encourage by large pharmaceutical companies civil society groups has recently filed a competition (and local production). and medical device producers to patent opposition in Brazil on the main There is a lot at stake: South Africa has delay - and influence - South African patent related to TAF. In addition, in the largest number of people living with patent reforms). South African Health November 2015, GTPI (Working Group HIV in the world, and Brazil guarantees Minister Aaron Motsoaledi has accused on Intellectual Property), a civil society HIV treatment for all, with many people the multinational pharmaceutical coalition, filed a patent opposition to on salvage therapy, as well as first- and companies in South Africa of conspiring deny a patent to BMS (for atazanavir; second-line treatment. But delays in against the state and the people of ATV) that could extend the patent patent law reform will undermine access South Africa, and called on all South holder’s monopoly until 2024. Brazil to affordable medicines, including ARVs. Africans to fight back “…to the last currently pays $496.40 pppy for 50 drop of their blood.” the 300mg version of ATV; a Health SOUTH AFRICA Ministry-approved licence between In 2015, 3.1 million people living BRAZIL BMS and the Brazilian government- with HIV were accessing antiretroviral Brazil is consistently excluded from linked pharmaceutical laboratory therapy through South Africa’s public voluntary licensing programmes, and Farmanguinhos forbids production of sector,47 and the government recently therefore forced into tiered pricing atazanavir in newer formulations and announced a ‘test and start’ policy.48 schemes from originator companies combinations, such as ATV/r.51 As more people are treated, the need for second-line and salvage regimens will increase. Many of these ARVs are patented and are too expensive for the government to procure for the public sector. But South Africa has not introduced or implemented key measures to safeguard public health, including fully adopting TRIPS flexibilities, and especially substantive examination of patent claims. In 2008 alone, South Africa granted 2,442 patents, while Brazil granted only 272 patents between 2003 and 2008.49

In 2009, South Africa’s Department of Trade and Industry (DTI) initiated a process to reform the country’s IP law and policy. In 2011, TAC, Section 27 © Stefan Heunis and MSF co-launched the ‘Fix the Patent Laws’ campaign, which now includes 18 MSF and the Treatment Action Campaign launched the ‘Fix the Patent Laws’ campaign other non-governmental organisations. to demand patient-focused reforms to South Africa’s patent laws. The campaign highlights how pharmaceutical companies have used evergreening tactics to exploit South Africa’s patent system. In September EVERGREENING 2013, the DTI released a draft policy Many countries often do not expired, but they are not because document for public comment. But the examine patent claims strictly, of evergreening. new policy is still not finalised, and is not leaving them vulnerable to In Ukraine, home to nearly expected until mid-2017. ‘evergreening’, whereby 265,000 people living with HIV,40 pharmaceutical companies make The longer DTI delays, the longer it GSK extended its abacavir (ABC) minor changes to medicines that will take for South Africa to introduce patent monopoly by eight years are already on the market to extend short- and long-term reforms that with its secondary patent on the their patents. Several ARVs should can accelerate and promote generic hemisulfate salt.41 Ukraine’s price now be free from patent barriers for originator ABC is $277.40 competition, and to drive down prices (including ABC, DRV, EFV and pppy42 versus $123.42 pppy for for patented drugs. The delay also raises RTV) since their basic patents have concern about undue political and the generic version.43 commercial pressure from multinational

Continued overleaf

Untangling the Web of ARV Price Reductions | msfaccess.org/utw2016 13 Patent oppositions and patent law reform continued

At the same time, multinational In November 2014, a multinational Argentina adopted new patentability drug companies are using lawsuits group of pharmaceutical companies examination guidelines for the to challenge measures that promote (INTERFAMA, the Pharmaceutical pharmaceutical sector to prevent the generic competition in Brazil, including Research Industry Association) filed granting of numerous patents that the country’s patent examination a Collective Action against ANVISA, do not meet specific criteria such as process. Since 2001, ANVISA, Brazil’s questioning the legitimacy of ANVISA’s novelty, inventive step, and industrial national drug regulatory agency, has participation in the patent granting application. Since Argentina’s new TRADE AGREEMENTS TRADE AGREEMENTS participated in analysing pharmaceutical process. Local civil society groups have guidelines were enacted, 95% of patent applications, instead of leaving strongly reacted to these setbacks. ARV patent applications have been this task exclusively to patent office rejected, an increase from the 51% Patent law reform that would improve examiners, and ANVISA has rejected rejection rate in 2012.54 affordability of new medicines has more than 400 of them. ANVISA’s role been delayed for more than two years. in pharmaceutical patent examination In 2015, CAEME – the association In 2013, a ‘package’ of bills to amend has been considered an important of multinational pharmaceutical Brazil’s patent law was introduced. If safeguard to public health and access to companies in Argentina – filed a approved, it will ensure that Brazil has medicines.52 Multinational companies court case questioning the validity of clearer criteria for patent examination, have frequently contested ANVISA’s the patent guidelines. In response, and introduce important flexibilities rejections in court. In 2011, the Attorney civil society groups from Brazil into its national laws.53 General’s Office (AGU) issued a legal and Argentina launched the ‘Big opinion strengthening the position of Pharma Drop the Case’ campaign at pharmaceutical companies – although it ARGENTINA the 31st session of the UN Human proved unenforceable, the AGU has not Argentina has taken steps to Rights Council, to push CAEME and formally withdrawn its legal opinion. improve its patent laws. In 2012, INTERFARMA to abandon their actions.

TRADE AGREEMENTS

Governments, civil society and generics producers should use TRIPS flexibilities to improve affordability

PATENT OPPOSITIONS AND PATENT LAW REFORM/ LAW OPPOSITIONS AND PATENT PATENT of, and access to, needed medicines. But TRIPS flexibilities are endangered by free trade agreements (FTAs) that pose serious threats to access to affordable medicines. These FTAs include intellectual property provisions – so-called ‘TRIPS-plus’ provisions – that exceed countries’ obligations under World Trade Organization (WTO) trade rules.

EU-INDIA FTA TRANS PACIFIC access to generic medicines due to PARTNERSHIP the proposed inclusion of TPP-like Negotiations on the EU-India FTA intellectual property rules by Japan began in 2007. They have been stalled AGREEMENT (TPP) and South Korea. since 2012, in part due to public The TPP is a far-reaching trade agreement Countries that did not join the TPP – pressure, but may resume this year. across the Asia-Pacific region. If ratified, particularly India and key members The EU-India FTA could jeopardise the TPP will be the worst-ever trade agreement for access to medicines: it will of the Association of Southeast access to India’s affordable generic lengthen, deepen and expand intellectual Asian Nations – will be pushed to medicines for millions of people, by property and patent monopolies, and adopt similar standards in the RCEP limiting production, sale and export of prevent or delay access to affordable, negotiations, which would represent a medicines in the future. life-saving generic medicines for millions rollback of protections against extended of people.56 While the TPP agreement has patent terms and data exclusivity that In the past, the EU has demanded been signed by governments, it has yet to are part of past agreements. a range of intellectual property be ratified by any country. provisions that exceed India’s The RCEP negotiations will have serious repercussions globally, since obligations under TRIPS, including REGIONAL both India, the ‘pharmacy of the measures that would allow companies COMPREHENSIVE developing world’, and China, the to prevent legitimate export of ECONOMIC world’s largest producer of the active medicines to developing countries or PARTNERSHIP (RCEP) pharmaceutical ingredients (API) used bring legal action against people who The RCEP trade negotiations among to make medicines, are among the 16 buy or distribute generics.55 16 Asia-Pacific countries could threaten countries included in the negotiations.

14 Médecins Sans Frontières | July 2016 TRADE AGREEMENTS

COLOMBIA: COMPULSORY LICENCE THREAT INVITES US PRESSURE

In April 2016, a leaked letter Thailand, Ecuador), which has As of mid-June 2016, the Colombian from the Colombian Embassy discouraged other governments Minister of Health announced that described how the US Senate from issuing compulsory licences they had issued a ‘public interest Finance Committee and the to ensure affordable medicines. declaration’ regarding imatinib, United States Trade Representative As WHO states in its letter to without public information about were pressuring the Colombian Colombia’s Minister of Health, whether the government will issue government not to issue a “unaffordable high prices of a compulsory licence to allow compulsory licence* for the anti- essential medicines, including for manufacturing and import of price- cancer cancer drug imatinib.58 non-communicable diseases, are lowering generic versions of the A number of countries have also a legitimate reason for issuing a drug, or simply reduce the price of faced similar pressure (Brazil, compulsory licence”.59 the Novartis product.60

LDC EXEMPTION FROM PHARMACEUTICAL IP EXTENDED

Least-developed countries section 7) for pharmaceutical protect their TRIPS flexibilities in (LDCs) have been granted an products until 1 January 2033.57 complex FTA negotiations. exemption from certain obligations But the free-trade agreements LDCs in Asia, including Laos, under TRIPS, in recognition of that are being negotiated in many Bangladesh, Cambodia and Myanmar, their economic, financial and countries across the Asia-Pacific as well as countries in sub-Saharan administrative constraints and region, in particular RCEP [see Africa, should continue to use the their need to make or procure low Trade Agreements, page 14], waiver to the fullest extent possible cost generic medicines. Under this could undermine the LDC transition to improve access to medicines transition period, LDCs do not have period, unless UN agencies and and should resist any pressure to to apply or enforce TRIPS provisions civil society provide technical and prematurely introduce intellectual concerning patents (TRIPS section political support to negotiating property rules that would undermine 5) or test data protection (TRIPS countries, particularly LDCs, to access to generic medicines. © Aye Pyae Sone © Aye

Regular check-up session for HIV positive patients at Muse clinic in Myanmar.

* A compulsory licence (CL) is an effective option for increasing access to ARVs and other medicines in countries where they are patented. It is a legal mechanism to allow producers other than the originator company to make the drug or to import generic versions into a given country.

Untangling the Web of ARV Price Reductions | msfaccess.org/utw2016 15 STOCKOUTS

For years, many countries have faced shortages and stockouts of essential medicines. Stockouts can STOCKOUTS STOCKOUTS be caused by logistical and administrative challenges in procurement, supply chain management, or ‘last mile delivery’, and by medicines having only a single source (which may lead to shortages: these are generally those under patent, without compulsory or voluntary licences that allow generic manufacturers to supply them).

Because of stockouts, people may governments should make plans needed to ensure sufficient availability, receive smaller amounts of the for treatment transitions, ensure while achieving economies of scale. medicine they need, which means appropriate buffer stocks and give extra time-consuming trips to the clear clinical guidance on making In South Africa, the Stop Stockouts clinic. They may also be switched switches correctly. Project has empowered patients and to different, less-optimal doses or pushed for accountability in the supply regimens, or be told to buy the Generic manufacturers must work of medicines. The Project receives and medicines they need from the quickly to avoid shortages and publishes daily reports about drug private market with the promise of stockouts, using information about stockouts from people living with HIV reimbursement (which is usually not current and pipeline ARVs, dose and health care workers, conducts fulfilled), or go without medicine optimisation, changes in treatment comprehensive national surveys to altogether - which can lead to drug guidelines and eligibility, national and monitor the locations and extent of resistance and illness. global targets for treatment scale-up, stockouts, and works with National As countries upgrade their protocols and HIV epidemiology to anticipate and Provincial Departments of Health to reflect WHO’s new ARV guidelines, the quantity of API and final product to identify and implement solutions.61 © Mariska Van den Brink © Mariska Van

In South Africa, the Stop Stockouts Project – a consortium bringing together six civil society organisations – is pushing for more accountability on stockouts of medicines that impact people’s access to regular treatment.

16 Médecins Sans Frontières | July 2016 STOCKOUTS

MARKET SHAPING INSTITUTIONS – WHAT NEEDS TO HAPPEN The Global Fund to Fight AIDS, the GFATM and other donors. to overcome any access barriers to Tuberculosis and Malaria (GFATM), The GFATM may not be able to affordable medicines. UNITAID and the Medicines Patent guarantee that these countries will Recent GFATM correspondence Pool have played a central role in be able to access the lowest prices indicates that it may seek to optimise the provision of affordable ARVs for new medicines, including those tiered pricing policies from drug around the world, including use of under patent, and it may even companies, instead of overcoming quality-assured generic drugs by the facilitate problematic tiered commercial pricing strategies. The GFATM, PEPFAR and other funders. pricing strategies used by drug e-marketplace has been recently companies in lieu of promoting The GFATM’s market-shaping robust generic competition. criticised by the GFATM’s Office of actions go beyond its ability to the Inspector General for failing provide treatment for millions of There are clear warning signs that to implement competitive bidding people, and have an important the GFATM is unwilling or unable to processes for the first products impact on worldwide ARV access. defend generic competition for the offered over the website.62 countries it supports. The GFATM After years of contributing towards did not signal support for the LDC At best, if the e-marketplace can collective efforts to reduce medicine extension, and has been silent overcome the challenges it is facing, prices, the scope and remit of the about the Trans-Pacific Partnership it could provide minimal technical GFATM is increasingly less ambitious trade agreement. It has not fixes as to how governments and potentially counter-productive. explicitly supported the use of TRIPS purchase medicines, without Progress has stalled, especially for flexibilities, although this principle dealing with the underlying barriers middle-income countries, where has been endorsed since the GFATM that make them unaffordable in the pharmaceutical companies seek started. Instead, the GFATM has been first place. At worst, prices offered to charge high prices. Some of championing an ‘e-marketplace’ under the e-marketplace will be these countries have a high disease (currently known as wambo.org) to insulated from the demands of burden, limited ability to pay for make procurement more efficient. government and civil society if such ARVs, and decreasing support from But the e-marketplace is not expected products remain unaffordable.

UPDATE ON THE MEDICINES PATENT POOL’S NEW LICENCES The MPP voluntary licences The VL for tenofovir now includes Some MPP licences have been (VLs) offer some countries the tenofovir alafenamide (TAF) and disappointing. AbbVie’s new MPP opportunity to gain access to has an expanded geographic scope adult licence for LPV/r has a limited affordable generic versions of new that allows generic producers from geographic scope and may force ARVs, although many middle- South Africa and China to join. specific generics companies that sign income and upper-middle-income The VL for elvitegravir (EVT) was the licence agreement to forego the countries, such as China and Brazil, amended to include production in right to supply specific countries continue to be left out of these VLs China and South Africa, provided that they currently have the right and are therefore prevented from that products are made from to supply. Furthermore, a new MPP buying the generic drugs produced Gilead-licenced producers of active licence with Bristol-Myers Squibb for through manufacturers based in pharmaceutical ingredients (API). daclatasvir, a hepatitis C medicine, their countries. In March 2016, GlaxoSmithKline (with introduces a worrying precedent: On one hand, the MPP has added ViiV) announced that it would increase it allows BMS to sign sub-licence new VLs, and increased the the geographic scope of its voluntary agreements with generics companies geographic scope or added new licensing agreements to include all together with the MPP (the normal formulations to other licences. In lower-middle-income countries. The practice is to not allow branded 2014, the MPP announced a new MPP’s VL for DTG has been expanded companies to be involved in signing agreement with AbbVie, for two to include Ukraine, Morocco, a sub-licence agreement). MSF specific paediatric formulations Moldova, Armenia and 14 other is concerned that such a practice of LPV/r covering 102 low- and low- and middle-income countries. could allow branded companies to middle-income countries.63 Although this is a welcome first step, influence the practices of generics In late 2015, a separate agreement excluded upper-middle-income companies, including for unrelated was signed between MPP and AbbVie countries will still be forced into tiered products, and undermine the on the adult formulation of LPV/r pricing schemes, and price-lowering neutrality of the MPP in managing which only covers African countries.64 competition will be prevented. the sub-licence agreements.

Untangling the Web of ARV Price Reductions | msfaccess.org/utw2016 17 CONCLUSION

The global response to HIV/AIDS has reached a turning point. Ensuring sustainable access to affordable

CONCLUSION CONCLUSION generic ARVs will save millions of lives. Scaling up to 90-90-90 is projected to save over 1.1 million lives and prevent 873,000 new HIV infections in the next five years; keeping up the pace for 10 years will save more than 2.4 million lives (including the mothers of 1.7 million children), and prevent over 2 million new infections.65

To accomplish this, governments Market-shaping institutions must All governments and donors must must commit to scaling-up, keep their focus on securing and do their part to accelerate the global optimising, and maintaining access to ensuring a sustainable supply of HIV response and meet the challenge affordable generic ARVs in the long diagnostics and adult and paediatric of the 90-90-90 goals, including run, as HIV is a disease that requires ARVs in low- and middle-income fully implementing the latest WHO people to have constant access to a countries, and the pharmaceutical guidelines, putting in place effective range of treatment options. This will industry should commit to registering policies at the national level, and require governments to use TRIPS ARVs in all countries, and expanding ensuring all people living with HIV flexibilities, reform patent laws, and the scope of their voluntary licensing have access to the most effective reject harmful TRIPS-plus provisions agreements to include all low- and drugs, diagnostics, and models of care. proposed in various FTA negotiations. middle-income countries. N’gadi Ikram ©

18 Médecins Sans Frontières | July 2016 ANNEX: SUMMARY TABLE OF ALL PRICES ANNEX: SUMMARY TABLE OF ALL PRICES

Developing country prices in US$ per patient per year, as quoted by companies. This table contains comprehensive information about ARV pricing in developing countries. It includes adult and paediatric formulations and doses, suppliers and WHO pre-qualification status/ US FDA SRA approval. The prices for developing countries are in US $, per person, per year, based on WHO dosing recommendations, as quoted by companies. Currency conversions were made when the pricing information was received, using the currency converter from www.oanda.com.

Each originator company applies its own eligibility criteria for discounting ARVs. Countries that are eligible for a discount from one company may not be eligible for discounts from other companies. Usually, companies create two groups of discount-eligible countries, often called ‘Category 1’ (countries that are eligible for the deepest discounts) and ‘Category 2’ (countries that are offered a lesser discount).

Paediatric formulations are highlighted in pink. Prices for paediatric products are estimated, based on WHO-recommended dosing, for the 10 to 10.9 kg weight band. When it was not possible to calculate dosing for the 10 kg weight band, the unit price was used.

The ARVs that are included in the WHO list of Prequalified Medicinal Products or that have tentative or full US FDA approval (as of May 2016) are in bold.

ARVs in Daily Originator company Generic companies alphabetical order dose

Abacavir (ABC) ViiV Aspen Aurobindo Cipla Hetero

20mg/ml oral 289 249 228 123 12 ml solution (0.066) (0.057) (0.052) (0.028) 97 60mg tablet 4 (0.067)

BMS Atazanavir (ATV) Aspen Cipla Emcure Category 1 Category 2 countries countries

100mg capsule xx (0.267)

412 412 380 207 150mg capsule 2 (0.564) (0.564) (0.520) (0.283)

200mg capsule xx (0.677) (0.677) (0.670) (0.433)

170 219 300mg capsule 1 (0.467) (0.600) Atazanavir/ Cipla Emcure Hetero ritonavir (ATV/r) 213 213 219 300/100mg tablet 1 (0.583) (0.583) (0.600)

Darunavir (DRV) Janssen Aspen Hetero

75mg tablet xx (0.114)

150mg tablet xx (0.227)

438 973 400mg tablet 2 (0.600) (1.333) 663 658 1,217 600mg tablet 2 (0.908) (0.901) (1.667)

Merck Quality Sun Efavirenz (EFV) Aspen Aurobindo Cipla Emcure Hetero Macleods Microlabs Strides Category 1 Category 2 Chemicals Pharma countries countries Case-by- 30mg/ml suspension xx (0.094) case

50mg capsule xx (0.058) (0.057)

Case-by- 50mg tablet xx (0.114) case 81 57 200mg capsule 3 (0.074) (0.052) 394 Case-by- 113 200mg tablet 3 (0.360) case (0.103) 237 Case-by- 84 37 20 47 45 38 35 70 38 38 600mg tablet 1 (0.650) case (0.231) (0.100) (0.055) (0.129) (0.123) (0.105) (0.095) (0.192) (0.105) (0.103)

Untangling the Web of ARV Price Reductions | msfaccess.org/utw2016 19 ARVs in Daily Originator companies Generic companies alphabetical order dose

Etravirine (ETV) Janssen Aspen

25mg tablet xx (0.075)

438 438 100mg tablet 4 (0.300) (0.300)

Sun Lamivudine (3TC) ViiV Aspen Aurobindo Cipla Hetero Macleods Microlabs Strides Pharma

10mg/ml oral 216 23 46 32 26 10ml suspension (0.059) (0.006) (0.013) (0.009) (0.007)

75 55 27 28 29 23 23 27 26 150mg tablet 2 (0.102) (0.075) (0.037) (0.038) (0.040) (0.031) (0.031) (0.037) (0.035)

75 33 32 23 18 67 300mg tablet 1 (0.204) (0.092) (0.087) (0.063) (0.049) (0.183)

Abbvie Lopinavir/ Aurobindo Cipla Hetero Macleods ritonavir (LPV/r) Category 1 Category 2

ANNEX: SUMMARY TABLE OF ALL PRICES TABLE ANNEX: SUMMARY countries countries

80/20mg/ml 150 296 4ml oral solution (0.103) (0.203)

40mg/10mg capsule 467 8 heat-stable pellets (0.160)

100/25mg 108 278 151 155 143 3 heat-stable tablet (0.099) (0.254) (0.138) (0.142) (0.131)

200/50mg 231 740 243 268 280 293 4 heat-stable tablet (0.158) (0.507) (0.167) (0.183) (0.192) (0.201)

Quality Sun Nevirapine (NVP) Aspen Aurobindo Cipla Emcure Hetero Macleods Microlabs Strides Chemicals Pharma

10mg/ml 61 91 20ml suspension (0.008) (0.013)

50mg tablet for 73 30 4 oral suspension (0.050) (0.021)

200mg capsule 2

63 28 28 28 29 27 24 37 27 26 200mg tablet 2 (0.087) (0.038) (0.038) (0.038) (0.040) (0.037) (0.033) (0.051) (0.037) (0.035)

Merck Raltegravir (RAL) Hetero Category 1 Category 2 countries countries

25mg chewable Case-by- xx (0.300) tablet case

100mg chewable Case-by- xx (0.600) tablet case

Case-by- 973 400mg tablet 2 675 (0.925) case (1.333)

Abbvie Ritonavir (RTV) Category 1 Category 2 countries countries

80mg/ml oral Case-by- xx (0.091) solution case

100mg heat-stable 83 Case-by- 2 tablet (0.114) case

Gilead Quality Sun Tenofovir (TDF) Aurobindo Cipla Hetero Macleods Strides Chemicals Pharma Category 1 Category 2 countries countries

207 365 57 39 40 67 45 43 300mg tablet 1 46 (0.127) (0.567) (1.000) (0.155) (0.107) (0.110) (0.183) (0.123) (0.117)

20 Médecins Sans Frontières | July 2016 ANNEX: SUMMARY TABLE OF ALL PRICES ARVs in Daily Originator companies Generic companies alphabetical order dose

Sun Zidovudine (AZT) ViiV Aurobindo Cipla Hetero Macleods Microlabs Pharma

450 73 110 91 10mg/ml oral solution 24ml (0.051) (0.008) (0.013) (0.010)

40 60mg tablet 4 (0.027)

100mg capsule xx (0.093) (0.055)

250mg capsule xx (0.187)

69 67 75 63 50 300mg tablet 2 (0.094) (0.092) (0.103) (0.086) (0.068)

ABC/3TC ViiV Aurobindo Cipla Hetero

110 110 60/30mg tablet 4 (0.075) (0.075)

225 220 164 161 600/300mg tablet 1 (0.617) (0.602) (0.450) (0.442)

Gilead TDF/FTC Aurobindo Cipla Hetero Macleods Strides Category 1 Category 2 countries countries

319 548 72 70 64 77 67 300/200mg tablet 1 (0.875) (1.500) (0.197) (0.192) (0.175) (0.210) (0.183)

Merck Sun TDF/FTC/EFV Aspen Aurobindo Cipla Hetero Macleods Strides Category 1 Category 2 Pharma countries countries

613 1033 251 112 122 110 120 103 100 300/200/600mg tablet 1 (1.680) (2.830) (0.689) (0.307) (0.333) (0.300) (0.328) (0.283) (0.273)

Quality Sun TDF/3TC Aurobindo Cipla Hetero Macleods Microlabs Chemicals Pharma

57 58 46 50 47 84 52 300/300mg tablet 1 (0.155) (0.158) (0.125) (0.138) (0.130) (0.230) (0.143)

Quality TDF/3TC/EFV Aurobindo Cipla Hetero Macleods Chemicals

97 300/300/400mg tablet 1 (0.265)

110 110 106 106 161 300/300/600mg tablet 1 (0.300) (0.300) (0.292) (0.292) (0.440)

TDF/3TC + NVP Hetero (co-pack)

300/300 + 200mg 1 kit 124 co-pack (3 tabs) (0.340)

Quality AZT/3TC ViiV Aurobindo Cipla Emcure Hetero Macleods Microlabs Strides Sun Pharma Chemicals

54 46 46 60/30mg tablet 4 (0.037) (0.032) (0.032)

161 82 82 127 84 84 73 116 76 74 300/150mg tablet 2 (0.221) (0.113) (0.113) (0.173) (0.115) (0.113) (0.100) (0.159) (0.104) (0.102)

AZT/3TC/ABC Sun Pharma

420 60/30/50mg tablet 3 (0.383)

Quality Sun AZT/3TC/NVP Aurobindo Cipla Hetero Macleods Strides Chemicals Pharma

88 80 60/30/60mg tablet 4 (0.060) (0.055)

97 96 95 102 126 94 96 300/150/200mg tablet 2 (0.133) (0.132) (0.130) (0.139) (0.173) (0.129) (0.131)

AZT/3TC + EFV Aurobindo Strides (co-pack)

300/150 + 600mg 1 kit 164 170 tablets (co-packs) (3 tabs) (0.450) (0.467)

Untangling the Web of ARV Price Reductions | msfaccess.org/utw2016 21 REFERENCES

1. UNAIDS. Global AIDS Update 2016 [Online]. 14. ENCORE 1 Study Group, Carey D, Puls R, 24. UNAIDS. Fact sheet 2016 [Online]. Unaids. REFERENCES UNAIDS 2016 May 31 [cited 2016 June 7]. Amin J, et al. Efficacy and safety of efavirenz org. 2016 [cited 2016 June16]. Available Available from: http://www.unaids.org/ 400mg daily versus 600mg daily: 96-week data from: http://www.unaids.org/en/resources/ sites/default/files/media_asset/global-AIDS- from the randomised, double-blind, placebo- fact-sheet update-2016_en.pdf controlled, non-inferiority ENCORE1 study. Lancet Infect Dis. [Online] 2015 July [cited 25. Newell ML, Coovadia H, Cortina-Borja 2. UNAIDS. World AIDS Day Report [Online]. 2016 April 28]; 15(7):793-802. Available from M, Rollins N, Gaillard P, Dabis F; Ghent UNAIDS 2012 [cited 2016 May 1]. Available doi: 10.1016/S1473-3099(15)70060-5. International AIDS Society (IAS) Working from: http://www.unaids.org/sites/default/ Group on HIV Infection in Women and files/media_asset/JC2434_WorldAIDSday_ 15. Vitoria M, Hill AM, Ford NP, Doherty M, Khoo Children. Mortality of infected and uninfected results_en_1.pdf SH, Pozniak AL Choice of antiretroviral drugs infants born to HIV-infected mothers in Africa: for continued treatment scale-up in a public 3. UNAIDS. 90-90-90. An ambitious treatment a pooled analysis. Lancet [Online] 2004 [cited health approach: what more do we need to target to help end the AIDS epidemic [Online]. 2016 May 7];364:1236-1243. Available from: know? [Online] J Int AIDS Soc. 2016 Feb 2 UNAIDS. 2014 October [cited 2016 May 7]. http://www.thelancet.com/journals/lancet/ [cited 2016 May 4];19(1):20504. Available Available from: www.unaids.org/sites/default/ article/PIIS0140-6736(04)17140-7/abstract files/media_asset/90-90-90_en_0.pdf from doi:10.7448/IAS.19.1.20504. 26. Cotton MF, Violari A, Otwombe K, et al; 16. Lenox JL, Landovitz RJ, Ribaudo HJ, et al; for 4. Médecins Sans Frontières. Out of Focus. How CHER Study Team. (2013). Early time-limited millions of people in West and Central Africa the AIDS Clinical Trials Group A5257. A Phase III Comparative Study of the Efficacy and antiretroviral therapy versus deferred therapy are being left out of the global HIV response. in South African infants infected with HIV: [Online]. MSF; April 2016 [cited 2016 June 4]. Tolerability of Three Non-Nucleoside Reverse Transcriptase Inhibitor-Sparing Antiretroviral results from the children with HIV early Available from: http://www.msf.org/sites/msf. antiretroviral (CHER) randomized trial. Lancet org/files/2016_04_hiv_report_eng.pdf Regimens for Treatment-Naïve HIV-1-Infected Volunteers: A Randomized, Controlled Trial [Online]. 2013 Nov 9 [cited 2016 May 4]; 5. Cohen MS, Chen YQ, McCauley M, et al; team. Ann Intern Med [Online]. 2014 October 382(9904):1555-63. Available from doi: HPTN 052 Study Team. Prevention of HIV-1 7 [cited 2016 May 5];161(7): 461–471. 10.1016/S0140-6736(13)61409-9. infection with early antiretroviral therapy.N Available from doi:10.7326/M14-1084. Engl J Med [Online]. 2011 Aug 11[cited 2016 27. US Food and Drug Administration. Tentative May 4];365(6):493-505. Available from doi: 17. Mills AM, Nelson M, Jayaweera D, et al. Once- Approval Letter [Online]. USFDA 2015 May 10.1056/NEJMoa1105243. daily darunavir/ritonavir vs. lopinavir/ritonavir 21 [cited 2016 May 2] Available from: http:// in treatment-naive, HIV-1-infected patients: www.accessdata.fda.gov/drugsatfda_docs/ap 6. INSIGHT START Study Group, Lundgren 96-week analysis [Online]. AIDS. 2009 Aug 24 pletter/2015/205425Orig1s000TAltr.pdf JD, Babiker AG, Gordin F, et al. Initiation of [cited 2016 May 5];23(13):1679-88. Available Antiretroviral Therapy in Early Asymptomatic from doi: 10.1097/QAD.0b013e32832d7350. 28. US Food and Drug Administration Approved HIV Infection. N Engl J Med [Online]. 2015 and Tentatively Approved Antiretrovirals in Aug 27 [cited 2016 7 May];373(9):795-807. 18. Orkin C, DeJesus E, Khanlou H, et al. Final association with the President’s Emergency Available from doi: 10.1056/NEJMoa1506816. 192-week efficacy and safety of once-daily Plan. [Online]. USFDA. [cited 2016 May darunavir/ritonavir compared with lopinavir/ 2]. Available from: http://www.fda.gov/ 7. Pawlowski A, Jansson M, Sköld M, Rottenberg ritonavir in HIV-1-infected treatment-naïve InternationalPrograms/PEPFAR/ucm119231. ME, Källenius G. Tuberculosis and HIV co- patients in the ARTEMIS trial.HIV Med. htm infection. PLoS Pathog [Online]. 2012 Feb [Online] 2013 Jan;14 [cited 2016 May 5] [cited 2016 May 10];8(2):e1002464. Available (1):49-59. Available from: doi: 10.1111/j.1468- 29. Lallemant M. Treatment needs and strategies from doi: 10.1371/journal.ppat.1002464. 1293.2012.01060.x. for young children. Drugs for Neglected Diseases initiative (DNDi). [Online] October 8. TEMPRANO ANRS 12136 Study Group, Danel 19. Antela A, Aguiar C, Compston J, et al. The 2011[ cited 2016 May 22]. Available from: C, Moh R, Gabillard D, et al. A Trial of Early role of tenofovir alafenamide in future HIV Antiretrovirals and Isoniazid Preventive Therapy management. HIV Med [Online]. 2016 May; http://www.who.int/hiv/amds/children_ in Africa. N Engl J Med [Online]. 2015 Aug 27 [cited 2016 May 5]17 Suppl 2:4-16. Available oct2011.pdf [cited 2016 May 10];373(9):808-22. Available from doi: 10.1111/hiv.1240110.1111/ 30. Drugs for Neglected Diseases initiative from doi: 10.1056/NEJMoa1507198. hiv.12401/abstract (DNDi). World AIDS Day 2015: Study Begins 9. World Health Organization. Guideline on 20. Boffito M, Jackson A, Owen A, Becker S. New in Kenya for Recently-Approved Paediatric HIV when to start antiretroviral therapy and on approaches to antiretroviral drug delivery: Treatment [Online]. Press release. December pre-exposure prophylaxis for HIV [Online]. challenges and opportunities associated with 1, 2015 [cited 2016 May 6]. Available from: WHO; 2015 September [cited 2016 May the use of long-acting injectable agents. http://www.dndi.org/2015/media-centre/ 6]. Available from: http://apps.who.int/iris/ Drugs [Online]. 2014 Jan; [cited 2016 May press-releases/wad-2015/ bitstream/10665/198064/1/9789241509893_ 5] 74(1):7-13. Available from doi:10.1007/ 31. Clinton Health Access Initiative. ARV Market eng.pdf?ua=1 s40265-013-0163-7. Report: The state of the antiretroviral drug 10. World Health Organization. Consolidated 21. Ford SL, Sutton K, Lou Y, et al. Rifampin market in low- and middle-income countries, guidelines on the use of antiretroviral drugs (RIF) decreases cabotegravir (CAB) 2014-2019. [Online] November 2015. for treating and preventing HIV infection exposure following oral coadministration. Issue 6 [cited 2016 May 6] Available from: [Online]. WHO; 2016 June [cited 2016 June 17th International Workshop on Clinical www.clintonhealthaccess.org/content/ 10]. Available from: http://www.who.int/hiv/ Pharmacology of HIV and Hepatitis Therapy uploads/2015/11/CHAI-ARV-Market- pub/arv/arv-2016/en/ [Online]. Washington DC (Abstract O18): Report-2015_FINAL.pdf 11. World Health Organization. AIDS medicines 2016 June 8-10 [cited 2016 June 15] Available and diagnostics service. The availability from: http://regist2.virology-education.com/ 32. UNAIDS, Clinton Health Access Initiative and and use of HIV diagnostics: a 2012/ 2013 Abstractbook/2016_6.pdf UNTIAID. Three new agreements announced with the potential to expand access to WHO survey in low- and middle-income 22. Margolis DA, González-García J, Stellbrink innovative HIV treatment in low- and middle- countries [Online]. Technical report. HJ, et al. Cabotegravir + rilpivirine as 2014 December [cited 2016 June 6]. income countries [Online]. 2015 November long-acting maintenance therapy: LATTE-2 Available from: http://apps.who.int/iris/ 30 [cited 2016 May 8]. Available from: http:// week 32 results [Online]. Conference on bitstream/10665/147213/1/9789241507905_ www.unaids.org/en/resources/presscentre/ Retroviruses and Opportunistic Infections eng.pdf pressreleaseandstatementarchive/2015/ (CROI) 2016 [cited 2016 May 6]; February november/20151130_PR_CHAI_UNITAID 12. Médecins Sans Frontières. Making Viral Load 22-25. Boston, MA. (Abstract 31LB). Available Routine. [Online] MSF Durban; June 2016. from: http://www.croiconference.org/ 33. Médecins Sans Frontières Access Campaign. [cited 2016 June 16] Available at: http://www. sessions/cabotegravirrilpivirine-long-acting- As HIV burden overwhelmingly shifts msfaccess.org/common-tags/hiv-viral-load maintenance-therapy-latte-2-week-32-results to ‘middle-income’ countries, access to 13. Llibre JM, Pulido F, García F, et al. Genetic 23. Mobula L, Barnhart M, Malati C, et al. Long- affordable medicines is under threat [Online]. barrier to resistance for dolutegravir. AIDS Acting, Injectable Antiretroviral Therapy for the MSF; July 22 2015 [cited 2016 May 2]. Rev [Online]. 2015 Jan-Mar [cited 2016 April Management of HIV Infection: An Update on a Available from: http://www.msf.org/en/ 30] 17(1):56-64. Available from: http://www. Potential Game-Changer [Online]. 2015 [cited article/hiv-burden-overwhelmingly-shifts- aidsreviews.com/resumen.asp?id=1290&indice 2016 Apr 30]. J AIDS Clin Res 6 466. Available ‘middle-income’-countries-access-affordable- =2015171&u=unp from doi: 10.4172/2155-6113.1000466. medicines-under#A

22 Médecins Sans Frontières | July 2016 REFERENCES

34. Moon S, Jambert E, Childs M, von Schoen- 45. Mohd Hanafiah K, Groeger J, Flaxman AD, 57. World Trade Organization. Council for Angerer T. A win-win solution?: A critical Wiersma ST. Global epidemiology of hepatitis Trade-Related Aspects of Intellectual Property. analysis of tiered pricing to improve access to C virus infection: new estimates of age-specific Extension of the Transition Period Under medicines in developing countries. [Online] antibody to HCV seroprevalence. Hepatology. Article 66.1of the TRIPS Agreement for Least Global Health. 2011 Oct 12 [cited 2016 June [Online] 2013 Apr [cited 2016 June 4] Developed Country Members for Certain 15];7:39. Available from doi: 10.1186/1744- ;57(4):1333-42. Available from doi: 10.1002/ Obligations with Respect to Pharmaceutical 8603-7-39. hep.26141. Products. [Online] 6 November 2015 [cited 2016 June 15]. Available from: http://www. 46. Hill A, Simmons B, Gotham D, Fortunak 35. Drugs.com [Online].[cited 2016 May 8] puntofocal.gov.ar/doc/ipc73.pdf Available from: https://www.drugs.com/price- J. Significant reductions in cost of generic guide/atripla production of sofosbuvir and daclatasvir for 58. Knowledge Ecology International. April hepatitis C treatment in low- and middle- 27, 2016. Letter from Colombian Embassy 36. Hill A, Ananworanich J, Ruxrungtham income countries. European Association for the regarding Senate Finance, USTR pressure on K, Simmons B, Ford N. Is the pricing Study of the Liver (EASL). International Liver Novartis compulsory licence [Online]. KEI. of antiretrovirals equitable? Analysis of Congress 2016 [cited 2016 April 29]; 13-17 May 11 2016. [cited 2016 May 8] Knowledge antiretroviral drug prices in 20 low and April, Barcelona Spain.(Poster abstract S113). Ecology International. Available from: http:// middle income countries. [Online] 7th keionline.org/node/2504 International AIDS Conference (IAC), 2016 47. Malan M. HIV-infected South Africans on 59. Goldman A. WHO to Colombia Minister [cited 2016 June 15]; June 30- July 3. Kuala ARVs could double [Online]. Bhekisisa. 2015 of Health: Unaffordable drug prices are a Lumpur, Malaysia. (Abstract WELBD05) September 30 [cited 2016 June 16]. Available legitimate reason for issuing a compulsory Available from: http://pag.ias2013.org/ from: http://bhekisisa.org/article/2015-09- licence [Online]. Knowledge Ecology Abstracts.aspx?AID=3102 30-hiv-infected-south-africans-on-arvs-could- double International; 2016 [cited 2016 Jun 8]. Available 37. Merck. Merck’s Investigational Once-Daily from: http://keionline.org/node/2580 48. Child K. Government updates HIV policy to Formulation of Isentress® (raltegravir) Meets allow ARV treatment for all South Africans 60. Cobb JS. Colombia to set new price for Novartis Primary and Secondary Endpoints in Pivotal [Online]. Times LIVE. 2016 May 10 [cited 2016 cancer drug: minister. Reuters [Online] June Phase 3 Study. Press release [Online]. February June 16]. Available from: http://www.timeslive. 9 2016 [cited 2016 June 14]. Available from: 22, 2016 [cited 2016 June 4] Available from: co.za/local/2016/05/10/Government-updates- http://www.reuters.com/article/us-novartis- http://www.mercknewsroom.com/news- HIV-policy-to-allow-ARV-treatment-for-all- colombia-cancer-idUSKCN0YV2NT release/research-and-development-news/ South-Africans mercks-investigational-once-daily-formulation- 61. Treatment Action Campaign, Doctors without isentress-r 49. Correa CM. Pharmaceutical Innovation, Borders/Médecins Sans Frontières A, Rural Incremental Patenting and Compulsory Health Advocacy Project, Rural Doctors Grinsztejn B, De Castro N, Arnold V et 38. Licensing. South Centre. [Online] Research Association of Southern Africa, SECTION al; ANRS 12 180 Reflate TB study group. paper 41. [cited 2016 Jun 1] 2011. Available 27, Southern Africa HIV Clinician’s Society. Raltegravir for the treatment of patients co- from: http://apps.who.int/medicinedocs/ Stockouts in South Africa. [Online] Second infected with HIV and tuberculosis (ANRS 12 documents/s21395en/s21395en.pdf Annual Report 2014. Stockouts Survey. June 180 Reflate TB): a multicentre, phase 2, non- 2015 [cited 2016 May 10]. Available from: comparative, open-label, randomised trial. 50. Knowledge Ecology International/ James Love. http://www.msf.org/sites/msf.org/files/ Lancet Infect Dis. [Online] 2014 June [cited New Leaked Merck missive reveals deep drug, stockouts_2014_final_online.pdf 2016 Jun 10];14(6):459-67. Available from medical device company opposition to South 62. The Global Fund. Office of the Inspector doi: 10.1016/S1473-3099(14)70711-X. African patent reforms [Online]. KEI. 2014 January 20 [cited 2016 May 8]. Available from: General. Limited scope review of the processes 39. Rägo L. Update on PQ programme and http://keionline.org/node/1908 undertaken to procure services and resources regional harmonization of drug registration. for the implementation of wambo.org. Report. Global forecasts of antiretroviral demand for 51. Information provided by the Brazilian [Online] June 13, 2016 [cited 2016 June 15]. 2014-2018, projection modelling for new Ministry of Health through the access to Available from: OIG_GF-OIG-16-016_Report_ antiretroviral formulations for 2015-2024 information law. en.pdf and update on hepatitis B & C [Online]. 52. Chaves GC, Vieira MF, Reis R. Access to 63. Medicines Patent Pool. The Medicines Patent WHO: WHO/UNAIDS Annual Meeting With medicines and intellectual property in Brazil: Pool (MPP) Signs Licensing Agreement Pharmaceutical Companies and Stakeholders; reflections and strategies of civil society. with AbbVie for HIV Paediatric Formulations 19-20 March 2015, [cited 2016 June 5] [Online] Sur, Rev. int. direitos human. vol.5 of Lopinavir and Ritonavir [Online]. Geneva. Available from: http://www.who.int/ no.8 São Paulo June 2008 [ cited 2016 June Medicinespatentpool.org. 2014 December 1 hiv/amds/14_rago-PQ-RH-updates2015.pdf 15]. Available from: http://www.scielo.br/pdf/ [cited 2016 June 16]. Available from: http:// sur/v5n8/en_v5n8a09.pdf 40. UNAIDS. Country progress reports. Ukraine. www.medicinespatentpool.org/mpp-signs- [Online] 2015 [cited 2016 June 16]. Available 53. Médecins Sans Frontières Access Campaign. licensing-agreement-with-AbbVie-for-HIV- paediatric-formulations-of-lopinavir-and- from: http://www.unaids.org/sites/default/ Why Brazil Should Reform its Patent Laws ritonavir/ files/country/documents/UKR_narrative_ [Online]. Issue Brief: MSF; 2015 [cited 2016 report_2015pdf May 4]. Available from: www.msfaccess.org/ 64. Medicines Patent Pool. The Medicines content/brazil-should-reform-its-patent-laws Patent Pool and AbbVie Sign Licensing 41. Medicines Patent Pool. Patent Status of ARVs Agreement to Increase Access to Crucial [Online]. Medicinespatentpool.org. 2016 54. Working Group on Intellectual Property (GTPI). HIV Treatments Throughout Africa [Online]. [cited 2016 June 16]. Available from: http:// GTPI announces campaign event at at the UN Medicinespatentpool.org. 2015 December www.medicinespatentpool.org/patent-data/ Council for Human Rights. [Online] March [cited 2016 June 16]. Available from: http:// 2016 [cited 2016 June 15] Available from: patent-status-of-arvs/ www.medicinespatentpool.org/mpp-and- the deolhonaspatentes.org/gtpi-anuncia- abbvie-sign-licensing-agreement-to-increase- 42. The Global Fund. Health Products campanha-em-evento-no-conselho-de-direitos- access-to-crucial-hiv-treatments-throughout- Management. [Online] Price and Quality humanos-da-onu/ Reporting. Price reference report. [cited africa/ 55. Médecins Sans Frontières Access Campaign. 2016 June 15] Available from: http:// 65. Wallensky RP, Borre ED, Bekker L-G, et al. The As EU-India free trade talks get closer to bi-ext.theglobalfund.org/analytics/saw. anticipated clinical and economic effects of 90- resuming, MSF warns access to medicines dll?Dashboard 90-90 in South Africa. Ann Intern Med [Online]. under threat [Online]. MSF; 2016 January 2016 May 31 [cited 2016 June 7]. Available 43. Tsokos P. (MSF). Email communication with [cited 2016 May 8]. Available from: www. from doi:10.7326/M16-0799. MSF. June 2016. msfaccess.org/about-us/media-room/press- 44. Médecins Sans Frontières Access Campaign. releases/eu-india-free-trade-talks-get-closer- Don’t shut down the pharmacy of the resuming-msf-warns-access developing world [Online]. MSF; 2015 [cited 56. Médecins Sans Frontières Access Campaign. 2016 May 6]. Available from: www.handsoff. Spotlight on Trans-Pacific Partnership msf.org/Questions%20and%20Answers%20 Agreement. Trading Away Health [Online]. on%20India,%20Intellectual%20Property%20 MSF. January 2016 [cited 2016 May 5]. and%20Access%20to%20Affordable%20 Available from: www.msfaccess.org/spotlight- Medicines on/trans-pacific-partnership-agreement

Untangling the Web of ARV Price Reductions | msfaccess.org/utw2016 23 GLOSSARY AND ABBREVIATIONS

3TC: Lamivudine, a nucleoside DTG: Dolutegravir, an HIV NDRA: National Drug Regulatory analogue reverse transcriptase inhibitor. integrase inhibitor. Authority.

ABC: Abacavir, a nucleoside analogue DTI: Department of Trade and Industry. PEPFAR: The President’s Emergency reverse transcriptase inhibitor. Plan for AIDS Relief. EFV: Efavirenz, an HIV non-nucleoside AIDS: Acquired Immune reverse transcriptase inhibitor. PI: Protease inhibitor. Deficiency Syndrome. EMA: European Medicines Agency. PPPY: Per person, per year. GLOSSARY AND ABBREVIATIONS GLOSSARY ANVISA: Brazil’s national health ETV: Etravirine, an HIV non-nucleoside RAL: Raltegravir, an HIV integrase surveillance agency, responsible reverse transcriptase inhibitor. inhibitor. for approval and oversight of pharmaceutical products, medical EU: European Union. RCEP: Regional Comprehensive devices, health services, food, Economic Partnership. Evergreening: Making minor changes cosmetics, and tobacco. to medicines that are already on the RTV or /r: Ritonavir, an HIV ARV: Antiretroviral; medicines that market, to extend patents. protease inhibitor used only at a treat HIV/AIDS. low dose to boost levels of other FTAs: Free trade agreements. HIV protease inhibitors. ART: Antiretroviral therapy; a FTC: Emtricitabine; a nucleoside combination of ARVs used to treat SRA: Stringent regulatory authority. analogue reverse transcriptase inhibitor. HIV/AIDS. TAF: Tenofovir alafenamide, a pro-drug Generic drug: According to WHO, ATV, ATV/r: Atazanavir, an HIV of tenofovir. a generic drug is a pharmaceutical protease inhibitor; atazanavir/ritonavir, product that is usually intended to be TB: Tuberculosis. a boosted HIV protease inhibitor. interchangeable with the originator TDF: Tenofovir; a nucleotide analogue AZT: Zidovudine, a nucleoside product. reverse transcriptase inhibitor. analogue reverse transcriptase inhibitor. GFATM: The Global Fund to Fight TPP: Trans-Pacific Partnership. BMS: Bristol Myers-Squibb. AIDS, Tuberculosis and Malaria. TRIPS: Trade-Related Aspects of CAEME: Association of multinational GSK: GlaxoSmithKline. Intellectual Property Rights. pharmaceutical companies in Argentina. HCV: Hepatitis C virus. UNAIDS: Joint United Nations Category 1: In this document, HIV: Human Immunodeficiency Virus. Programme on HIV/AIDS. ‘Category 1’ refers to the countries that are eligible to receive the deepest INTERFARMA: The Pharmaceutical UNITAID: a market-shaping institution discount on a company’s ARV price. Research Industry Association; a that facilitates and accelerates multinational group of pharmaceutical availability of medicines and diagnostics Category 2: In this document, companies located in Brazil. for HIV/AIDS, tuberculosis, malaria and “Category 2’ refers to countries that are hepatitis C. not eligible for a company’s deepest IP: Intellectual property. discount on ARV pricing, but are US: United States. LDCs: Least-developed countries. nevertheless offered a lesser discount. US FDA: United States Food and LPV/r: Lopinavir/ritonavir, a boosted DAAs: Direct-acting antivirals, oral Drug Administration. HIV protease inhibitor. drugs used to treat hepatitis C virus. VL: Voluntary licence. MPP: Medicines Patent Pool. DRV, DRV/r: Darunavir, an HIV WHO: World Health Organization. protease inhibitor; darunavir/ritonavir, MSF: Médecins Sans Frontières; a boosted HIV protease inhibitor. Doctors Without Borders. WTO: World Trade Organization.

24 Médecins Sans Frontières | July 2016 ACKNOWLEDGEMENTS:

Front cover photo: © Peter Casaer/MSF

Back cover photo: © Aye Pyae Sone/MSF

Design/artwork/print: ACW Ltd +44 (0)20 8392 4330 www.acw.uk.com

DISCLAIMER: “Untangling the Web of Antiretroviral Price Reductions” is a pricing guide and cannot be regarded as a company price list nor as a clinical guideline. It is crucial that any purchaser verify prices and availability as well as quality status directly with the supplier before procurement. Médecins Sans Frontières has made every effort to ensure the accuracy of prices and other information presented in this report, but MSF makes no representations or warranties, either expressed or implied, as to their accuracy, completeness or fitness for a particular purpose. Inclusion of a product in this document does not indicate MSF purchases or uses the product. Information on patent status of the products mentioned in this guide is indicative only and not exhaustive, and should be verified with relevant national patent of prices when used for other than reasons of general information. Clinical decisions should not be made based on this document.

Untangling the Web of ARV Price Reductions | msfaccess.org/utw2016 MSF Access Campaign Médecins Sans Frontières Rue de Lausanne 78, CP 116 CH-1211 Geneva 21, Switzerland

Tel: + 41 (0) 22 849 84 05 Fax: + 41 (0) 22 849 84 04 Email: [email protected]

www.msfaccess.org

Facebook “f” Logo CMYK / .ai Facebook “f” Logo CMYK / .ai www.facebook.com/MSFaccess twitter.com/MSF_access