Building African AIDS Care from the Ground Up

http://www.annals.org/

Jennifer Fisher Wilson

15 July 2003 | Volume 139 Issue 2 | Pages 157-160

The epicenter of AIDS activity in the early 1980s was San Francisco General Hospital, where Merle Sande, MD, was chief of medicine. The mystifying disease appeared at higher rates there than any place else in the United States, and Sande and his staff helped pioneer its clinical treatment. Within the next decade, physicians in the United States learned how to treat HIV infection and AIDS as pharmaceutical companies launched drugs that controlled the infection without curing it. Triple combination antiretroviral therapy, introduced in 1996, led to a 70% decrease in deaths from HIV/AIDS. But at the same time as these successes in the United States, AIDS was ravaging many other countries, particularly in Africa.

Almost 25 years later, Sande, now professor of medicine at the University of Utah, is again working at the epicenter of AIDS activity. Along with Ugandan and North American colleagues, he is running an HIV/AIDS clinic at Mulago Hospital in Kampala, Uganda, and teaching local physicians advanced techniques to manage the disease. Uganda was hit early and hard by HIV/AIDS. At one time, the virus infected as many as 1 in 3 people in some regions, and more than 100 000 Ugandans died of AIDS every year throughout the 1990s. Furthermore, Uganda sits squarely in sub-Saharan Africa, the region of the world most affected by HIV/AIDS.

Even though HIV/AIDS is much better understood now, Sande’s work in Kampala is in many ways even more challenging than his earlier work in San Francisco: The national health care system of Uganda is rudimentary by comparison, especially outside of the urban centers, and only 1% of the people with HIV can afford to pay for antiretroviral therapy, which costs about $1 a day. But Sande, who has worked in Kampala on and off since the late 1980s, is already seeing signs of progress. In 2 years, the HIV/AIDS clinic at Mulago Hospital has grown to treat more than 2000 patients, about 150 of whom are receiving antiretroviral therapy. The training program has graduated 100 clinicians who are dispersed throughout Africa. Sande is opening an AIDS information center funded by the Bill & Melinda Gates Foundation and staffed by two pharmacists and a physician on standby to answer questions about HIV/AIDS from clinicians throughout sub-Saharan Africa. And by the end of 2003, he hopes to open the doors on the country’s—indeed the continent’s—first state-of-the-art, large-scale HIV/AIDS clinic, which is being built with funds from an $11 million Alternative Treatments from Pfizer, Inc. "We’re trying to re-create here what we did in San Francisco, and we’re making fantastic progress," said Sande.

Such progress, though, is really just a small drop in a very large bucket. Consider the following. In western nations, about 500 000 people were using antiretroviral agents and 25 000 people died of AIDS in 2001. At the same time in sub-Saharan Africa, only 25 000 people were using antiretroviral agents and 2.2 million people died of AIDS. Uganda is actually far better off than many other African countries: A long-term, government-led health education effort has resulted in a decrease in the prevalence of HIV infection to about 8%. In Botswana, on the other hand, prevalence of HIV infection increased from 18% in 1992 to 35% in 2002 in some areas. In Zambia, life expectancy dropped to 33 years from 44 a decade ago as a result of a 20% HIV prevalence. In Zimbabwe, deaths from HIV infection have orphaned more than 780 000 children. In South Africa alone, 4.7 million people—a quarter of the population—are infected with HIV. And these figures provide only a glimpse of the staggering HIV/AIDS toll in Africa.

Luckily—if there is any bright side to the AIDS crisis in Africa—an expanding group of people are focused on limiting the continent’s spread of infections and on reducing suffering and mortality from HIV/AIDS. Furthermore, efforts to bring modern HIV/AIDS treatment to Africa appear to be supported by a wide range of international factors that, together, might prevent millions of deaths from HIV/AIDS in the coming years. Funding has grown exponentially in the past few years, and includes the new U.S. Emergency Plan for AIDS Relief, a 5-year, $15 billion global initiative signed into law by President Bush. The World Bank has committed $1 billion through its Multi-Country HIV-AIDS Programs for Africa. Meanwhile, pharmaceutical companies have slashed prices of antiretroviral agents to developing countries and in some cases have cooperated with manufacturers of generic drugs. Finally, more and more African political leaders are addressing the HIV/AIDS epidemic and working to improve care.

"Over the past year, we have moved into a situation where internationally, there’s the political will and momentum to transform HIV/AIDS care. Now we need to turn that into a reality," said Badara Samb, MD, a consultant with UNAIDS (Joint United Nations Programme on HIV/AIDS) and director of the Accelerating Access Initiative, a partnership between the United Nations and five pharmaceutical companies to increase access to HIV/AIDS care, treatment, and support.

Outside of Africa, one country has already turned political will and momentum into a reality and, in doing so, has energized the international AIDS community to act more boldly in Africa. Brazil stunned the world in 1996 by mandating universal access to free antiretroviral agents as part of its national AIDS program. To provide such access, Brazil not only negotiated reduced drug prices from pharmaceutical companies but also decided to make generic versions of some antiretroviral drugs domestically. The patents for antiretroviral agents were not specifically protected in Brazil, so Brazilians weren’t breaking the law. However, the practice began a still-active international controversy over drug patents. According to the latest reports, Brazil produces 7 of the 15 antiretroviral agents that it uses to treat people with HIV/AIDS, and the government purchases the rest on the international market, typically at reduced prices. In supplying drugs and other medical care to the more than 100 000 people with HIV/AIDS, the country spends more than $200 million annually, or about $2000 per person. Although this program is costly, Brazil spends less than one fifth of the amount spent on antiretroviral therapy in the United States.

"The program is difficult in many ways. In particular, it’s expensive. There are a lot of other diseases in Brazil, like malaria and tuberculosis, and they also need money. But the AIDS program works. And it shows something really important to the rest of the world: that this kind of mobilization is possible," said Jane Galvão, PhD, who worked with the Brazilian national AIDS program before taking a fellowship with the Fogarty Institute at University of California, Berkeley, in 2001 and then becoming affiliated with the Institute for Global Health in San Francisco. Since Brazil’s treatment access program began, average survival time for a patient with AIDS has increased from 6 months to 5 years. The mortality rate from AIDS has declined by 50%. And the Brazilian health minister estimates that the country is saving more than $1 billion by keeping HIV-infected people out of the hospital. Galvão attributed Brazil’s success to a combination of factors: adequate funding, political leadership, strong community involvement, and a health care system that incorporates education about HIV prevention, HIV counseling and testing, and treatment of sexually transmitted infections.

Brazil’s bold AIDS program proved for the first time that a developing country could deliver widespread HIV/AIDS care that included antiretroviral agents. It inspired the international AIDS community to call for universal antiretroviral access for other developing nations as well. AIDS activists in South Africa coalesced around the issue and jointly called for a program like Brazil’s in their own country. South Africa is one of the few countries in Africa with sufficient resources and medical infrastructure to mimic the Brazil model, but its political leaders have consistently ignored HIV/AIDS, to the point of denying that HIV causes AIDS and that AIDS could be treated. Now, a sophisticated, 4-year lobby by the Treatment Action Campaign (TAC) has pressured the South African government to address HIV/AIDS at last. After TAC organized a series of acts of civil disobedience earlier this year, the government met with TAC and agreed to craft a national AIDS program that includes support for drug treatment.

"Politically, there’s no going back in South Africa. Putting a public provision care model into place would hurt, but they could do it," said Josef Decosas, MD, the regional health advisor for Plan International in West Africa, who has worked with AIDS issues throughout Africa for the past 13 years. Decosas estimated that an AIDS program would cost about 2% of South Africa’s gross national product but that improved health, decreased mortality, and increased productivity in HIV-infected individuals would partly allay these costs.

Most other African countries lack the resources to successfully replicate the Brazilian model. Moreover, the number of people with HIV in many African countries is much larger than in Brazil. The main hope for these countries rests on sustained assistance from international sources. "In these countries, the most important thing right now is to really push toward strengthening the primary care infrastructure to the point where you could possibly support ARVs [antiretroviral agents]. Before you even think about providing ARVs in most countries, just some treatment for oral candidiasis—which can cause starvation in people with AIDS—would make such a difference in reducing suffering. I mean, if you can’t get chloroquine to people with malaria, you can’t even think about getting people antiretroviral drugs," Decosas said.

Decosas is not the only person to suggest that the current focus on antiretroviral access for Africa may be premature. While the benefits of antiretroviral therapy are clear—widespread use would save hundreds of thousands of African lives almost immediately—many African countries need a coherent primary health care system in which to administer antiretroviral therapy over the long term. A primary barrier to effective antiretroviral treatment is not only the cost of drugs but also the necessary oversight by trained physicians who specialize in HIV/AIDS care.

"There’s a need for a medical infrastructure that can handle HIV/AIDS in many countries in Africa. We’re developing a prototype now in Uganda, and we hope to take it to other countries," said Sande, who, along with co-director Nelson Sewankambo, MD, dean of the Makerere University School of Medicine, formed the Academic Alliance to AIDS Care and Prevention in Africa, a coalition composed of a dozen professors of medicine, pediatrics, and public health from North America and Uganda. "We’re preparing so that there will be a health care infrastructure for treating HIV and AIDS patients when the money eventually comes in to pay for antiretrovirals," Sande said.

Even with a good health care infrastructure, adherence to antiretroviral treatment regimens remains a crucial issue in international AIDS care. In places such as Uganda, even drugs purchased at a substantial discount are still expensive compared with wages. Moreover, many of the individuals receiving antiretroviral agents take unscheduled treatment breaks when they run out of money, resuming treatment once they receive another paycheck. The uncontrolled drug market in some West African countries means that antiretroviral agents will soon be available from any pharmacy, but few people will be able to afford them, and even fewer will follow an effective treatment regimen, Decosas said. Even in Brazil, where the public health care system oversees distribution of free medications, adherence to antiretroviral therapy remains a challenge. "We have a good basic health care system, but it’s not like it’s paradise," Galvão said.

Still, with a vaccine for HIV/AIDS apparently still decades in the future, drug access is the primary goal of many people who work in the field. "The main issue is that now that drugs are more affordable, why aren’t we making more headway in regards to making them available for the people who need them so badly. We can’t let any obstacles get in our way," said Mark Wainberg, PhD, director of the McGill AIDS Centre in Montreal, Canada, and past president of the International AIDS Society. Wainberg’s microbiology laboratory at McGill University has studied the effects of intermittent antiretroviral therapy. While hardly ideal, intermittent therapy is not as dangerous as once believed. "One of the great lessons that we’ve learned is that it is better to have drug access even under conditions of non-100% adherence than to have no drug access at all," Wainberg said.

People who aren’t consistently following an antiretroviral regimen might develop resistant viruses, and those resistant viruses may be sexually transmitted to others, he said. His research suggests, however, that some forms of resistant viruses may be less virulent. "Getting a drug-resistant virus is never a good thing, but that might be a silver lining in the cloud," he said.

Preventing HIV infection in the first place is the ultimate goal of the international AIDS community. But for the time being, at least, their focus is on a multipronged approach that emphasizes treatment as well as prevention, according to Wainberg. Without treatment, more than 6000 people, mostly in Africa, die of HIV/AIDS every day.

Money for antiretroviral agents may be available more quickly than anyone could have hoped. Sande noted that the Global Fund recently committed $36 million to Uganda’s HIV/AIDS program in February 2003, and various other organizations, such as the World Bank, are also expected to contribute soon. Some of that funding will go toward the purchase of antiretroviral agents. The outlook is similarly promising throughout sub-Saharan Africa. Meanwhile, Brazil continues to provide leadership in AIDS care. Last summer, it committed to sharing its expertise by pledging $1 million—10 grants of $100 000 each—to assist governments in their AIDS programs, including transfer of technology for those that wish to follow Brazil’s lead by learning how to produce antiretroviral agents domestically.

Many pharmaceutical companies have reduced the price of antiretroviral agents for developing countries, but no uniform preferential pricing system exists. This has resulted in a confusing pricing system wherein countries may qualify for some price reductions but not others. Doctors Without Borders (Médecins Sans Frontières [MSF]) publishes "Untangling the Web of Price Reductions" in an effort to provide clear information on antiretroviral pricing on the international market. In particular, the publication provides data on antiretroviral prices offered by originator companies and some generic companies in low- and middle-income countries. The goal of the price guide is to help governments and other bulk purchasers access antiretroviral agents.

Except for Merck & Co. and Roche, most originator companies do not have a policy on antiretroviral price reductions for countries that are outside sub-Saharan Africa or that are not classified as Least Developed Countries, according to MSF. To determine whether a country is eligible for reductions, Merck & Co. uses the Human Development Index, a criteria related to resources, and HIV/AIDS prevalence statistics; according to these sources, an estimated 120 countries would theoretically qualify. GlaxoSmithKline uses the criteria of Least Developed Country classification and the geographic classification of sub-Saharan countries; an estimated 63 countries would qualify according to these sources. Various countries, such as some Central American countries, that do not fall into these categories but are considered needy may benefit from price reductions negotiated by the Accelerated Access Initiative, a collaborative effort of UNAIDS and the major pharmaceutical industries. Various other factors, such as national distribution and handling charges, mark-up rates, and taxes, may ultimately change the cost of medications to patients.

In "Untangling the Web of Price Reductions," MSF notes that equity pricing has been the most effective method for pushing prices down. MSF’s definition of equity pricing incorporates three simultaneous strategies: 1) stimulation of generic competition; 2) differential pricing, which addresses all developing countries, according to clearly defined policies or voluntary licensing of proprietary products; and 3) government readiness to override patents by issuing compulsory licenses or making government use of a patent when affordable prices are not offered for patented products. During the past 3 years, generic competition has been the most effective means of reducing prices of antiretroviral agents, MSF notes. (According to an international agreement, Least Developed Countries are not obligated to patent drugs until 2016.)

To illustrate how generic competition has resulted in cheaper antiretroviral agents, MSF has tracked the lowest world price of a typical combination therapy. In May 2000, the combination of stavudine plus lamivudine plus nevirapine cost a total of $10 439 per patient per year, and only the original, patent-holding pharmaceutical companies made the drugs. By July 2000, Brazil had started making some antiretroviral agents domestically and offered a version of the triple-drug therapy for $2767 per patient per year. Just a few months later, the Indian drug maker Cipla offered a generic version of the combination therapy for $350 per patient per year. Shortly thereafter, the prices charged by the originator companies for the antiretroviral agents fell dramatically to $931. By March 2001, the originator price had dropped again, to $727. Since then, this amount has remained stable while the generic cost has dropped somewhat further, to $201 in April 2003 (Source: "Untangling the Web of Price Reductions: A Pricing Guide for the Purchase of ARVs for Developing Countries." 4th ed. Médecins sans Frontières; 15 May 2003).