Envisage

HIV/AIDS in South Africa: Progress Through Collaboration

by Elisa Ludwig

January 2008

According to the UNAIDS 2006 Report on the Global AIDS Epidemic, as many as six million people in South Africa have been infected with HIV. In the Khayelitsha township, where pharmacist and Médecins Sans Frontières (MSF) advocacy coordinator Marta Darder works, the situation is especially grim. Antenatal HIV prevalence is 30 percent—almost double the national average—and patients also battle high rates of co-infection with tuberculosis.

Opened in 2001, MSF’s clinic in Khayelitsha was the nation’s first to provide antiretrovirals (ARVs) at a primary level, and is considered by the MSF and others as being one of the most successful models for treatment provision. The clinic’s operations since have been transitioned with technical assistance from MSF to the provincial government, but the enormous challenge to scale up the program and reach as many patients as possible remains.

“We have not gotten control of the disease yet,” Darder says. “There are more people in treatment, and not only are the number of patients higher but the length of treatment is longer, with more people with treatment fatigue who need [more expensive] second-line drugs.”

Access Barriers

The Khayelitsha clinic is reflective of the situation across the country, where gaining access to ARVs is difficult for all but the most privileged patients. While South Africa is unique among both developed and developing nations for its constitutional guarantee of health care, when it comes to the provision of HIV/AIDS treatment the government has shown historical resistance—famously characterized by then deputy president Thabo Mbeki’s controversial suggestion that HIV did not cause AIDS, and health minister Dr. Manto Tshabalala Msimang’s assertions that beetroot and garlic would protect against the disease.

Civil society groups like The Treatment Action Campaign and The AIDS Law Project have fought vigorously to ensure that these views do not influence health policy and programs, without a great deal of support. “Our government resisted an evidence-based approach to dealing with the epidemic for many years,” says Jonathan Berger, senior researcher and head of policy, research and communications at The AIDS Law Project in Johannesburg, South Africa. The South African government did not introduce ARV treatment to the public health sector until 2004, just over three months after the South African cabinet adopted the Operational Plan for the Comprehensive HIV and AIDS Care, Management and Treatment, the country’s comprehensive plan for tackling AIDS. By then, the epidemic was raging and almost 25 percent of all South African children under age 15 had lost at least one parent to AIDS.

Fueling the crisis is a shortage of health care workers as well as a lack of infrastructure to expand and scale up treatment programs. Though the country is classified as a middle-income nation, the legacy of apartheid has created a great disparity of resources and wealth. The private sector currently employs half of the country’s nurses and two-thirds of its doctors.

Last year, the Ministry of Health unveiled a new strategic plan, including a goal to initiate 650,000 patients on ARV therapy by 2011. But even with the government on board, clinics will need to obtain and sustain a constant high-quality, low-cost supply of ARVs—drugs that an enormous patient population will need for a lifetime.

Patents and Prices

Outside of South Africa’s unique political situation, a key reason drug access has been a problem in South Africa is a result of patent law that has kept prices inflated and therefore unaffordable for many patients. One million people in the nation need ARV treatment, and market forces are simply not providing it. Though more than 300,000 people are accessing ARVs through private health care and community-based clinics like the one in Khayelitsha, some 735,000 people are going without, according to MSF. “The issue now is not really about market forces working or not working, but that the market can never provide to very poor people who are entirely reliant on the state for the provision of health care services,” Berger says.

The pharmaceutical industry has been criticized for impeding access to its products. “We see drugs approved by FDA in 2003 that just arrived here in 2007,” Darder says. An example is tenofovir disoporxil fumarate (TDF), which was registered in South Africa three years after Gilead Science announced it would be made available to patients at a preferential cost. It was then held up in bureaucratic delays for 18 months at the Medicines Control Council before it was finally licensed in the spring of 2007.

The AIDS Law Project is currently pursuing a competition case against Merck Sharp and Dohme (MSD), a subsidiary of Merck & Co., Inc, and Abbott for refusal to license companies to produce or import generic efavirenz (Sustiva) and lopinavir/ritonavir (Kaletra) respectively. Though MSD has granted a license to local generic company Aspen Pharmacare, in the absence of competition, the price of the product, which has not yet reached the market, remains extremely high for the public sector, which spends a disproportionate share of its ARC budget of efavirenz. “It’s an interesting issue,” Berger says. “It comes down to this: To what extent can you use anti-trust law to challenge the exercise of rights granted by patent law and under which circumstances can you compel someone to license?”

Another hurdle to large-scale ARV treatment is the need for generic combination fixed-dose drugs—best-practice treatments that combine several compounds and allow patients to take a single pill rather than multiple pills ensuring both ease of use and a cheaper cost for a regime. But fixed-dose combinations often are held up by the same patent issues and lack of market competition as individual drugs, particularly when they involve licensing from different companies for each component. “Here in Khayelitsha, we would like to have a fixed-dose combination of emtricitabine, tenofovir and efavirenz. But we will not have it in the short term and not in the long term without a fight,” Darder says.

Critics also decry the lack of pediatric formulations of ARVs. Without ARVs, half of all children with HIV/AIDS die before the age of two. As pediatric AIDS is less prevalent in the developed world, research companies have developed far fewer formulations for children. According to the World Health Organization (WHO), as of 2005, there are 2 million children with HIV in sub-Saharan Africa. And of the 21 innovator ARVs, 11 are approved for use in children and only three are approved for children under age two. Furthermore, there are no second-line pediatric treatments in the pipeline.

Industry Action

For its part, industry has responded to ongoing criticisms with a number of different strategies, ranging from improving access and reducing costs to advocacy and support programs. MSD and Roche offer no-profit pricing for ARVs, and Roche does not seek patents on some HIV medicines, including ARVs in the least-developed countries and sub-Saharan Africa.

“We have regularly reduced prices over the years, and we’ve kept our pricing very open and transparent,” says Maria Vigneau, director of Access and Sustainability in Resource-Limited Countries at Roche in Basel, Switzerland. “We believe it’s what we can do to maintain a long-term sustainable model. Donating ARVs would not be.” In addition, Roche announced in January 2006 that it would be creating a technology transfer initiative to teach African companies to make saquinavir for distribution in their respective countries.

Other industry efforts address South Africa’s health workers shortage with training programs. Boehringer Ingelheim has provided HIV education to health professionals as well as financial support for medical students. MSD conducts medical education for doctors through the HIV Clinicians Society. “We are also involved in efforts to respond to the pandemic through financial assistance to the Regional AIDS Initiative of Southern Africa as well as supporting an HIV/AIDS prevention youth program, run by the University of Cape Town HIV Coordinating Unit,” says Sam Nkalashe, corporate responsibility manager for MSD in Halfway House, South Africa.

Bristol-Myers Squibb operates a “Secure the Future” program, a comprehensive effort that has committed US$150 million to fighting HIV/AIDS in nine countries, including South Africa, and the program encompasses a nursing curriculum, medical fellowships and community health centers. Separately, Abbott and Boehringer Ingelheim donate ARVs and diagnostics to clinics across Africa.

Yet for activists and health care workers in the field, some of the efforts outside of drug access initiatives amount to charity work that does little to mitigate the vast need for medications. To some observers, these programs look like PR-generated gestures rather than genuine good will. “It would be more useful if companies were ensuring access to good-quality and fair-price drugs—that’s their core business and any other efforts deviate attention from their core business,” Darder says. “They can train physicians but many people can do trainings. It’s needed, yes, and very welcome, but we still must look at the difficulties people have obtaining the drugs.”

Darder says industry could better support the fight against HIV/AIDS by simply improving drug access—without legal action to prompt price drops or licenses. “In 2004, when GSK and Boehringer Ingelheim gave licenses to generic companies, it didn’t happen because of incentive or initiative from the pharmaceutical industry—it was because they were taken to the Competition Commission for abuse of pricing with a consequence of death,” Darder says. “We have to fight for drugs one after the other.”

Indeed, other observers encourage the pharmaceutical industry to take proactive steps on its own, instead of simply reacting to litigation. “I think the general experience is that industry has been totally recalcitrant at every single stage. Every single modest progressive step has been a response to pressure from activists and generic competition without exception,” says Robert Weissman, an intellectual property lawyer and co-director of Essential Action in Washington, D.C., USA. Essential Action advocates for accelerated generic competition for ARVs through its Access to Medicines Project. Weissman points out that there is still resentment about the 2001 Pharmaceutical Manufacturers versus Nelson Mandela case, in which 39 companies challenged an act that allowed for compulsory licenses. The case was eventually settled out of court but remains symbolic of industry self-interest, he says. “What was remarkable was the unity of industry, and that none of the companies broke away from it despite massive publicity hits.”

Generic Solutions

When it comes to improving access, licensing drugs to generic companies—rather than offering tiered pricing programs in which drugs are still too expensive for patients—may be preferable from an economic standpoint. “Discount pricing programs are designed to maintain brand-name company control and forestall generic competition,” Weissman says. “Pricing programs are designed to enable importation rather than generic competition. Often the pricing drops overnight, and that shows that these are just discretionary decisions by companies making substantial profits.”

Beyond licensing more products, Weissman argues that creating more transparency about patent status and product registration will send a message of positive intent from industry. “It’s virtually impossible for most countries to find out what the patent status of a particular product is, and the inability to have that information makes it just as impossible to make rational procurement or licensing decisions.” While he acknowledges that the national product registration process can be slow in most countries, he believes companies should prioritize poorer countries.

Berger has seen some progress in the fight for drugs. He points to examples of companies that have acted without having to face direct action, such as BMS granting two royalty-free licenses for its drug atazanavir, to Indian company Emcure, and to Aspen Pharmacare. “When put to the test, most companies ultimately do respond in appropriate ways. We have seen a lot of movement but not always on key drugs that are necessary,” Berger says. “Still, I think companies, especially those that are [entering the African market later], have learned what came before and they are speaking to organizations like us up front. There does seem to be some willingness to engage and listen and be open to concerns.”

In absence of government leadership on the issues of drug access, Berger says organizations like his need to devote huge levels of resources to maintain pressure on companies. Without such pressure, companies will simply fall back on old habits, Berger says. “HIV really threatens sub-Saharan Africa in a massive way. This is a continent that’s already in a lot of trouble and needs all the assistance it can get—not obstacles,” he says. “Yet when you look at what Africa [adds to] pharmaceutical sales globally, it really is a market with very little impact on the industry’s bottom line. The attitude that ‘we have to defend [our] patents vigorously everywhere in the world’ has never made sense.”

Vaccine Quest

The development of an AIDS vaccine is one of the greatest public health goals of our time. The International AIDS Vaccine Initiative (IAVI), a global non-profit working to accelerate vaccine development, has estimated that even a vaccine that was 50 percent effective given to 30 percent of the world’s population could cut the number of new HIV infections in half within 15 years. Given the current IAVI-estimated rate of 11,000 new HIV infections every day, the implications of a successful vaccine are enormous.

The unique challenges to developing a vaccine for HIV/AIDS are manifold, including the difficulties in pinning down a “moving target,” such as a hypervariable virus; incentivizing small biotech companies to innovate new products; a lack of an ideal animal model; the necessity for large, global trials in developing countries where the pandemic has hit hardest; and securing funding for long-term research.

“The history of vaccines is successes built on failures,” says Dr. Pat Fast, director of medical affairs at IAVI in New York, N.Y., USA. There are currently more than 30 candidate vaccines in clinical trials, including Sanofi-Aventis’ canarypox vector with Vaxgen’s gp120; and Merck’s Ad5 vector, both of which are being tested for efficacy. “If the most promising vaccines we are currently testing in efficacy trials turn out to work well—and we’ll know this in less than three years—then we can move ahead with final testing and manufacturing,” Fast says. “The development of an HIV vaccine can best be described as a marathon, not a sprint.”

Like the HIV vaccine, the hunt for an effective microbicide—a vaginal gel used to prevent HIV infection—is a vast, international effort. A microbicide would play an important role in protection against the HIV virus, particularly for women who have multiple partners, or who live in a culture or in a relationship where discussion about condoms is discouraged. In South Africa, for instance, more than 50 percent of people with HIV are women, and the impact of a successful microbicide would be invaluable in stemming further infections.

Microbicide development received a blow this year, however, as a Phase III clinical trial testing the effectiveness of cellulose sulphate was halted when the drug showed an increased the risk of infection for the women participating in the trial. “These results were certainly worrying for the field,” says Sheena McCormack, clinical epidemiologist at Microbicides Development Programme in London, U.K. Nonetheless, over 60 candidates are now being tested in the United States, Africa and India, with one Phase II trial and five Phase III trials. The ideal microbicide would protect against most HIV strains as well as other sexually transmitted pathogens and have no effect on the vagina or rectal mucosal epithelium. (An early candidate, nonoxynonol-9 created epithelial disruption, leading to greater risk of HIV infection).

McCormack is the chief investigator in trials for PRO2000/5, a sulphonated polymer, and initial results are expected in 2009. “Any of these trials could lead to a licensed microbicide,” she says. “It difficult to know the exact impact because there is usually some underreporting when it comes to people’s sexual behaviors, but in my view the potential for microbicides to fight HIV infection as well as other disease is huge.”

While the development of a microbicide certainly could have an enormous impact on HIV prevention throughout Africa, it is but one front in a war against AIDS. Major advances in lessening the burden of the disease also requires multiple public/private partnerships to improve patient access to antiretrovirals and an increased focus on vaccine research. It is without question, however, that substantial action must happen urgently.

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