The incidence of HIV infection has been rising sharply these years in China, which causes increased antiretroviral drugs demand and therefore, increased cost. The Chinese government has offered free antiretroviral therapy to HIV/AIDS patients since 2003. The high cost of antiretroviral drugs, especially new, second line drugs is a big challenge for HIV prevention and control in China. To fill the gap between demand and supply of antiretroviral drugs, China now seeks to produce generic antiretroviral drugs which would be much cheaper than brand name drugs by its native pharmaceutical companies under compulsory licenses
by Hongzhou Lu*
Shanghai Public Health Clinical Center affiliated to Fudan University
Since the first AIDS case in China reported in a traveler from abroad who subsequently died in Beijing in 1985, the prevalence of HIV infection has been increasing significantly. There are currently an estimated 780,000 people living with HIV in China with 9,224 deaths in 2011, making HIV/AIDS the leading killer of the infectious diseases. 1
To fight against the HIV/AIDS epidemic, the Chinese government initiated the ‘Four Free and One Care’ policy: provision of free antiretroviral (ARV) drugs for all rural residents and poor people in cities, free counseling and testing services, free treatment for pregnant women and testing for their babies, free school fees for children affected by HIV and AIDS, and financial support for affected families in December 2003. Although it declared that only rural residents and poor people in cities were eligible to get free ARV drugs, in fact, every HIV patients whose CD4 T cells count is below 350 cells/mm3 could get ARV drugs for free after his/her identity be recorded. By the end of 2011, a total of 126,000 patients have received free antiretroviral therapy (ART) in China, which plays an important role in HIV/AIDS prevention and control.1
However, despite the spreading of free ART, some patients still do not receive ART because of complicated factors, e.g. fear of privacy leak out, etc. More important, the majority of HIV/AIDS patients in China are under ART with the first-line ARV drugs, which are relatively cheaper and more toxic than the second-line drugs.
Available ARV drugs in China include didanosine (ddI, seldom used now because of its toxicity), stavudine (d4t, replaced by other nucleoside/nucleotide reverse transcriptase inhibitors gradually), zidovudine (AZT), tenofovir (TDF), efavirenz (EFV), nevirapine (NVP), indinavir (IDV), abacavir (ABC), kaletra (lopinavira/ritonavir) and raltegravir (RAL). But, in the government free ART program, TDF and kaletra are second line drugs which are available only under some medical conditions, while RAL is not included. Meanwhile, a number of patients cannot tolerate the first line drugs because of their toxicities. And, after usage of ARV drugs for a long time, drug resistance can occur. Therefore, second line ARV drugs are in urgent need in China.
Although the national budget for HIV/AIDS prevention and control increased from 4.8 million US dollars to 349 million dollars from 2003 to 2011, it is still not affordable for the Chinese government to offer every patients with second line ARV drugs since they are six times more expensive than the first line ones, especially from 2013 when the Geneva-based Global Fund to Fight AIDS, Tuberculosis and Malaria will no longer give China grants to fight HIV. 2 Generic drugs which are much cheaper than the brand-name drugs may well provide a solution to this problem.
Currently, there is still a huge gap between the demand and supply of generic ARV drugs in China, and only generic AZT, ddI, D4T, 3TC and NVP are available. The biggest barrier for native manufacturers to produce generic drugs is patent protection. As a member of the World Trade Organization (WTO), China has been required by WTO rules (the Trade-Related Aspects of Intellectual Property Rights, or TRIPS) to prevent local manufacturers from producing generic drugs of expensive brand-name drugs whose patents still exist. 3 However, the 2001 Doha agreement allows a country to issue a compulsory license for a drug that treats a disease causing a severe health emergency in that country.4 Meanwhile, following the ‘paragraph 6 waiver’ issued by the WTO, member countries who are unable to produce pharmaceuticals at home and are suffering from a serious health crisis can import generics from other nations under compulsory licenses.5 These two agreements allow China either to self-produce generic ARV drugs or to import from other countries under compulsory licenses, such as India, Brazil.
Although several drug makers have the ability to produce generic second line ARV drugs, few of them have applied to produce generic ARV drugs under compulsory licenses in China. They are reluctant to produce partially because the profit margins of generic ARV drugs are small compared with other home-made brand drugs and pharmaceutical raw materials. More important, it was difficult to apply for producing generic drugs according to the Chinese patent law in the past. As an example, application from native pharmaceutical companies to produce generic oseltamivir during influenza A H1N1 epidemic in 2009 was denied in China.
To encourage the production of generic ARV drugs, in March 2012 the State Intellectual Property of China amended the Chinese patent law, so allowing the government to issue compulsory licenses to eligible companies to produce generic versions of patented drugs during State emergencies, or unusual circumstances, or in the interests of the public.
Some report declared that the emendation of Chinese patent law was to encourage the production of generic tenofovir, which is recommended by the World Health Organization as part of a first-line cocktail treatment for HIV/AIDS patients.6 In fact, in 2011, Gilead Sciences signed up for an agreement allowing for the production of generic versions of Viread (tenofovir) on payment of royalty in 111 countries, but not China.7 Anyway, after the emendation of patient law, some eligible drug makers would be willing to make generic ARV drugs, as the potential market in China is expanding.
With the increasing HIV/AIDS cases in the following years, while international funds withdraw, China needs to reallocate its fund on free ARV drugs properly, especially as “treatment as prevention” has become now the most significant shift in the thinking and strategies of many public health workers.
Note: Compulsory licensing is when a government allows someone else to produce the patented product or process without the consent of the patent owner. It is one of the flexibilities on patent protection included in the WTO’s agreement on intellectual property - the TRIPS Agreement.4
1.UNAIDS. (2011)HIV in China: Facts and Figures
2.WHO(2011, April)HIV Drug Resistance Factsheet
3. WTO. Material on the WTO website.
4.WTO(2006)Compulsory licensing of pharmaceuticals and TRIPS
6.Reuters. China changes patent law in fight for cheaper drugs
7. www.waifaction.org/pages/s.0007/t.5298.html
————————————————————————
*Corresponding author:
Address correspondence to Hongzhou Lu. Department of Infectious Diseases, Shanghai Public Health Clinical Center affiliated to Fudan University, Caolang Road 2901, Jinshan District, Shanghai, 201508, P.R China.
Tel: 86-21-37990333 ext 3222
Fax: 86-21-57248758
E-mail: luhongzhou@fudan.edu.cn
The study supported by:
“The promotion and optimization of standardized treatment strategies of patients co-infected with HIV and tuberculosis” (2012ZX10001003-002); Chinese Twelveth Five Key projects on Infectious Disease From Chinese Ministry of Health
PI: Hongzhou Lu