Patents versus Patients? Antiretroviral Therapy in India

[Guest guest]

Dear colleagues

Forwarding a peer-reviewed article from New England journal of Medicine, Volume

353:749-751 August 25, 2005 Number 8

_______________

Patents versus Patients? Antiretroviral Therapy in India

Diane V. Havlir, M.D., and M. Hammer, M.D.

Legislation passed by the government of India rarely draws international

attention, let alone global outrage. But in December 2004, to comply with the

requirement of the World Trade Organization (which India had joined in 1995)

that its member countries adhere to trade-related aspects of intellectual

property rights (TRIPs), the president of India issued a patent-amendment

ordinance requiring 20-year patents on all new medications. The ordinance went

into effect

January 1, 2005. Objections were voiced around the world by advocacy groups for

patients with human immunodeficiency virus (HIV) infection, who characterized

the proposed law as pitting patents

against patients. As a result, in March 2005, the Indian Parliament passed a

more lenient bill — but one that could still pose major obstacles for access to,

and the development of, new generic drugs and that could stimulate lengthy

litigation and increase the costs of new drugs substantially, thus threatening

recent progress.

Figure (Removed. Moderator)

Over the past three years, a revolution in commitment, new funding, and price

reductions for antiretroviral therapy has permitted expanded HIV-treatment

programs to take root in many countries. The U.S. President's Emergency Plan for

AIDS Relief (PEPFAR); the Global

Fund to Fight AIDS, Tuberculosis and Malaria; the World Health Organization's 3

by 5 Initiative; the Glaser Pediatric AIDS Foundation; and Médecins

sans Frontières, among others, have paved the way for large-scale access. The

unmistakable benefits

of the efforts of these groups have included a reduction in suffering and death,

a substantial decrease in the transmission of HIV to infants, and improved

medical care in resource-limited settings.

Sustaining access to effective HIV drugs — and ensuring their affordability — is

a central challenge faced by those who strive to roll out antiretroviral

therapy. Experience has taught us that a formulary of antiretroviral drugs is

needed to transform HIV

infection from an inevitably fatal disease to a chronic illness. Front-line

antiretroviral regimens work quite well for many patients but can have

short-term and long-term toxic effects and can lead to

drug resistance that necessitates the use of new medications if the benefits are

to be sustained. Data from high-volume outpatient clinics in the United States

document the need for frequent changes in therapy. Many HIV-infected persons in

the United States are alive today as a result of an expanded formulary, and they

are dependent on the active pipeline of drug development for continued health.

In resource-limited settings, the focus of HIV-treatment programs has been to

provide access as quickly as possible, for as many people as possible, to a

first-line regimen. Generic drugs are chosen

because of their low cost. In the late 1990s, the Brazilian government launched

an ambitious program to provide universal access to antiretroviral therapy. The

local production of generic antiretroviral agents generated great controversy

over intellectual-property rights, but it withstood a challenge from the U.S.

government, which argued that such production infringed patent-protection

agreements. This successful program now delivers therapy to more than 150,000

patients through the public health system and

has impressively reduced HIV-related morbidity, mortality, and hospital and

medical costs.

Generic antiretroviral agents are now being used in Africa and Asia as well, and

many of them have been manufactured in India, where, since 1970, the Indian

Patents Act has permitted the production of generic versions of drugs. Because

only slight modifications

in manufacturing could qualify a product for a new patent, Indian companies were

able to offer HIV drugs at prices as low as 4 percent of those of brand-name

drugs. The practice by Indian manufacturers of

coformulating antiretroviral drugs could reduce patients' pill burdens, the

likelihood of dosage errors, and theoretically, the risks of treatment failure

and drug resistance. The new Indian patent

legislation may well slow, if not threaten very substantially, the development

of new products with these benefits.

What does all this mean for the millions of HIV-infected persons in current or

imminent need of lifesaving antiretroviral therapy? Will patent laws and their

application block the pipeline of anti-HIV

drugs for resource-limited countries? Fortunately, the Indian response to TRIPs

does not pose a short-term danger for current efforts to expand access to

antiretroviral therapy. Drugs that are already in production are immune from the

new patent regulations

in India and may continue to be exported. Right now, this means that the most

commonly used coformulated preparations of antiretroviral agents should continue

to be available at reduced prices. Indeed, it is the other challenges to

treatment programs — limitations of workforce, diagnostic tests, clinic

infrastructure, and patient-monitoring tools — that represent the greatest

immediate obstacles to these efforts.

Although the simple first-line antiretroviral regimens in wide use today clearly

save lives, they may already be failing to meet all the needs of today's

HIV-infected patients, a proportion of whom may be intolerant of, or have

contraindications to, the available therapies. For example, concerns are

increasingly being voiced about the widespread use of stavudine, given its

propensity to cause peripheral neuropathy, stigmatizing lipoatrophy, and lactic

acidosis. Alternatives are needed now to avoid these complications and the

consequent disillusionment with large-scale antiretroviral rollouts that might

ensue.

Efavirenz carries a risk of teratogenicity for women of childbearing potential,

and nevirapine can cause severe rash and hepatotoxic effects. Finally, treatment

failure is occurring in resource-limited

settings, and there is a growing need for medications outside the scope of the

currently produced generic formulations. Without robust second-line therapeutic

regimens, patients lose the benefits of antiretroviral therapy and may transmit

drug-resistant virus to

others, jeopardizing the efficacy of front-line regimens. Persons with HIV

infection require decades of treatment, and the downstream consequences of a

limited formulary will take on increasing importance over the long haul.

" Sustaining " will soon surpass " scaling up " of antiretroviral therapy as the

major

challenge in some countries. Brazil is already facing this challenge, and

African and Asian countries with far fewer resources will probably encounter

even greater hurdles in gaining access to second-line therapies.

The risks posed by the TRIPs legislation to HIV-infected persons in

resource-limited countries cannot be ignored, but there are solutions to this

apparent conundrum. The simple fact is that we need to have it both ways. We

need to encourage quality-controlled manufacturing of generic versions of

current and future antiretroviral agents, since this has proved to be the most

efficient way to provide large-scale treatment at hugely discounted

prices. At the same time, we need to provide incentives for major pharmaceutical

companies to continue to develop antiretroviral drugs for the long-term benefit

of HIV-infected people globally.

Protection of intellectual-property rights and tiered pricing arrangements are

key elements in maintaining this commitment.

Although this paradox may seem insurmountable, there are already indications

that solutions can be found. For example, some pharmaceutical firms, such as

GlaxoKline and Gilead, have recently made licensing arrangements with

generic-drug manufacturers

such as Aspen. The Food and Drug Administration has approved, under PEPFAR,

several generic antiretroviral preparations for purchase and use outside the

United States. Imaginative strategies focused on the long term will be needed if

we are to fulfill our obligations, and solutions will require brand-name and

generic pharmaceuticals to coexist and prosper. Good economic policy, in this

instance, can mean equally good public health policy.

The world currently has a perfect opportunity to further stimulate ongoing

efforts by governments, the World Health Organization, and nongovernmental

organizations to ensure the sustainability of

HIV-treatment programs. Ambassador Randall Tobias, U.S. Global AIDS Coordinator

and formerly a chief executive in the pharmaceutical industry, was recently

elected chair of the Policy and Strategy Committee of the Global Fund. With

leadership responsibilities for

both PEPFAR and the Global Fund, Ambassador Tobias is in a unique position to

bring stakeholders together to search for common ground and sustainable new

policy directions. Such an initiative should be warmly received by all who are

committed to finding a long-term solution.

Currently, only 11 percent of persons in sub-Saharan Africa who need

antiretroviral therapy are receiving it. Ensuring that HIV-care initiatives

continue to take root globally is not only a moral imperative, but a political

and economic necessity as well.

Source Information

Dr. Havlir is a professor of medicine at the University of California, San

Francisco, and chief of the HIV–AIDS Division at San Francisco General Hospital,

San Francisco. Dr. Hammer is a professor of medicine at Columbia University

College of Physicians and Surgeons and chief of the Division of Infectious

Diseases at the Columbia University Medical Center, New York–Presbyterian

Hospital, New York.

An interview with Dr. Havlir can be heard at www.nejm.org.

http://content.nejm.org/cgi/content/full/353/8/749

_________________________

Greetings:

Phi Huynhdo

E-mail: <huynhdophi@...>