'Elusive and intangible hope'

Two days after Kofi Annan gave his speech in Abuja, Nigeria, proposing the creation of the Global Fund, an article appeared on the Associated Press news wire. "Experts Worry Vaccine Research Overlooked in AIDS Pandemic." Which experts? Why, pass the envelope, it's Seth Berkley, "president of the New York-based International AIDS Vaccine Initiative" who "said Friday from the sidelines of the African AIDS summit" that, in the AP's words, "efforts to develop an AIDS vaccine are at risk of being overlooked in the push to raise money to fight the epidemic." The article goes on to note that "the IAVI... has raised more than $300 million to assist vaccine research and create systems for distributing them to developing countries. Berkley estimated that the project would require at least double that figure to give research bodies a chance of developing vaccines by 2007."

Certainly nothing in the past few years of explosive growth for IAVI indicates that its funding is in any way jeopardized by the new efforts to provide desperately needed HIV prevention, treatment and care programs to places which need them now—not in the ten or twenty years it will take to develop, test, approve, and distribute a safe and effective HIV vaccine. And certainly no one who is fighting to build a global system to provide HIV prevention, care, and treatment for poor countries now fails to recognize the critical need for a safe, effective vaccine—or fails to support expanded AIDS research efforts which may lead to one.

But it is breathtaking that Dr. Berkley misses no opportunity to beat the drums for IAVI, even appearing to complain about Secretary General Annan's enlightened call for a massive mobilization to do something now. "Billions of dollars have gone into the development of effective AIDS treatments, but vaccine research has received relatively little funding," according to the AP reporter, no doubt thinking independently.

In the past few years, actually, NIH funding for clinical trials has remained flat, while funding for vaccine research has increased by 25-30% per year. In fact, the article itself goes on to point out that "about $250 million [went] towards vaccine research [last year]." In other words, if the NIH vaccine effort continues at $250 million for the next five years, NIH alone will have spent $1.5 billion on an HIV vaccine—plus IAVI's $300 million—and both figures are likely to grow significantly. Moreover, any global fund for HIV must, and most likely will, help to subsidize the distribution of a safe and effective HIV vaccine when and if it comes.

In the meantime, Dr. Berkley should support efforts to prevent HIV infections and to treat people infected with HIV. The only alternative is to let 35 million, or 100 million, or however many are infected before NIH, IAVI, and others develop and distribute a vaccine, simply die. Dr. Berkley should also consider what vaccine researchers are providing, other than elusive and intangible "hope" and the opportunity to enroll in twenty or 100 slots in a phase one vaccine study, to the devastated communities around the world where IAVI and other vaccine research programs such as the NIH-funded HIV Vaccine Trials Network operate.

For example, a phase one study is being carried out in Hlabisa, KwaZulu-Natal, South Africa, in a district where one third of adults are infected with HIV. Let us presume that the study will enroll 20 HIV-negative people, and that many more will be screened for potential eligibility. Let us assume that 100 people will be screened, and that 33 will turn out to be HIV-positive. Being HIV-positive, none of them will be eligible for the study. What is the vaccine research center going to do for them? I have asked this of Anthony Fauci from NIAID, and of Seth Berkley from IAVI, and they haven't been able to answer the question.

Another thing which could be done now: Let us suppose that some people become infected during the phase one trial of the candidate vaccine, which is unlikely to be completely protective—even if it's protective at all. Suppose that these seroconversions are detected within three to six months. There is a huge, on-going ethical debate about whether it's ethical not to offer antiretroviral therapy to people who become infected in the course of a vaccine study. This debate usually presumes that it's a question of either lifelong expensive treatment starting immediately versus no treatment at all, ever. This creates a false dichotomy.

Newer interventions, such as those pioneered by Bruce Walker and Eric Rosenberg at Harvard, suggest that it might be possible to treat a newly-infected person with one or two brief (weeks to months) cycles of HAART and turn them into long-term non-progressors. This would be a hypothesis well worth studying in a resource-poor setting, because for the cost of a few weeks or months of treatment (plus monitoring), recent seroconverters might be converted into long-term non-progressors, and might thus not require therapy for twenty years or more.

Even if they were average progressors, under current guidelines and with an average progression rate, half would not need treatment for ten years. But they could be followed and studied in natural history cohorts which promised them ongoing monitoring and effective treatment when they needed it. And by that time, drug prices will have come down, drug regimens and strategies will have improved, and some poor countries may have developed HIV/AIDS care and treatment programs.

It is simply narcissistic for advocates of vaccine research to attack the people and programs that are trying to provide prevention, care and treatment in the interim. And it's narrow-minded for vaccine researchers to focus "laser-like" on their goals without thinking of how their programs could be broadened to benefit the communities where they are taking place in the time between now and the discovery of a safe, effective vaccine. ¤

'No drugs in time for her'

In April, Kofi Annan, the UN Secretary General, said it would take just $7-10 billion a year to mobilize the resources necessary to reverse the ravages not only of HIV, but of tuberculosis and malaria. Also in April, a group of economists, doctors and others from Harvard said that it would take $1.1 billion to treat one million HIV-infected people in Africa. Mark Harrington took it upon himself to find out what these figures were based on—and to see how realistic they might be. The result was a captivating narrative of the rapid-pace developments over the past nine months, which finds its genesis in last July's protests and picnics in South Africa.

It's been an astonishing year for AIDS treatment activism, full of amazing highs and lows. One year ago, with great fanfare, five big drug companies, along with the World Health Organization and UNAIDS, announced that they would provide steep reductions in the cost of HIV/AIDS drugs in developing countries. In July 2000, ten thousand AIDS researchers and activists went to Durban, South Africa, for the 13th International AIDS Conference. On the opening evening of the conference, some of us marched with 5,000 South Africans from the Treatment Action Campaign (TAC), many of them chanting and singing in Zulu, and were demanding global access to AIDS drugs. Then those of us who were conference delegates filed into Kingsmead soccer stadium to hear South African President Thabo Mbeki refuse to make the connection between HIV and AIDS, or between pharmaceutical company prices and the plight of 35 million people with HIV around the world who could not afford treatment. Instead, he treated us to a lecture on poverty, reading from a World Bank report published in the early 1990s.

Over the course of the year, a global groundswell arose. No one was getting the drug discounts announced in May. Drug companies negotiated slowly, company by company, drug by drug, country by country. Meanwhile they held steadfast in their determination to litigate South Africa's 1997 medicines act, and successfully pressured the Clinton administration to haul Brazil before the World Trade Organization for its 1996 intellectual property law.

Then I went back to South Africa with my three colleagues from TAG and two from Project Inform. We spent two more weeks there with TAC, training 300 activists, health care workers, nurses, counselors, labor union officials, youth workers and PWAs about AIDS treatment. We met intensely political activists from Johannesburg who seemed to know more about the ballot controversies in Florida than we did, despite our being sated with CNN. We heard people tell us their doctors wouldn't give them Bactrim or ketoconazole because "You've got AIDS and you're going to die." And we heard Soweto pediatrician Glenda Gray tell us, and TAC, about the "memory boxes" her patients would make, filled with photos and memorabilia and tapes telling their children that they loved them, that they wished they could still be around, but that AIDS had taken them away, and blessing their children and wishing them good lives. We met women from rural KwaZulu-Natal who came out with HIV in front of 50 other participants at the workshop in Durban and begged for solidarity. We heard about AIDS orphans getting raped because some people thought that having sex with a virgin would take the HIV away.

Every day at the Cape Town workshop, the 150 participants filed in singing and chanting ANC freedom songs with the words changed so that they were about AIDS. A woman took me out during a break and told me about her depression. She had been positive for years. I said, maybe activism can help. She shook her head. It was the despair of knowing that there was no way the government was going to provide any treatment in time for her. At the end of each workshop, the TAC people stood and sang the beautiful anthem of the new South Africa, "Nkosi Sikelel' iAfrica," and we would cry.

On our last day in Cape Town we had dinner at Zackie Achmat and Jack Lewis' house in a beach community on the bay just south of Table Mountain. We were all set for a fish feast, a braai, with beer and wine and food and friends. When we got to their house everyone looked ashen. Yet another TAC member had died that day - just one of five that died in the two weeks we were in South Africa. We were having dinner with our friends and fellow activists, but nothing could bridge the gap between the privilege of our world and the struggle of theirs.

On February 6, 2001, the Indian drug company Cipla dropped a bomb by announcing that it would provide a good HAART regimen—d4T, 3TC, and nevirapine—for $1,200 to the private sector, for $600 to governments, and for $350 to NGOs such as Médécins sans Frontières (MSF). Cipla had already offered the brand-name companies a 5% royalty if they would let Cipla have voluntary licenses for their antiretrovirals in developing countries, but it had received no response.

Suddenly industry had to scramble. Their secret, vague, privately-negotiated, country-by-country discounts were suddenly exposed as the sham they were. In Washington, D.C., the Pharmaceutical Research & Manufacturers Association (PhRMA), along with several of its members, held a meeting called at very short notice with several HIV community groups which had not been working on global access issues and floated a trial balloon under which they would provide bigger discounts to Africa as long as the African countries abandoned their rights to use, make, or import generic drugs for AIDS. This initiative was quickly squelched when word got out to the broader community.

All of a sudden the drug companies began making much broader public offers. On February 21, at a press conference announcing a 13% rise in profit for the newly merged company, the new GSK CEO, Jean-Pierre Garnier, announced that they would reduce the price of Combivir by 90%—to $2/day—to NGOs and non-profits in poor countries—but no further—while rejecting Cipla's request for a voluntary license. This would bring the price of Combivir to about $730/year.

On March 15, Bristol-Myers Squibb (BMS) announced that it would sell its two nucleoside analogues, ddI and d4T, for just $1.00 a day together in Africa. That was half the price of GSK's offer for Combivir. BMS also stated that it wouldn't defend its patents in Africa or block African countries from importing generic equivalents. (Upon examination, BMS admitted that it didn't have any patents on ddI in Africa, and the only country where it had a d4T patent was South Africa.)

Abbott Laboratories, which hadn't even been part of the big five announcement in May 2000, was last to join the parade, announcing on March 28 that it would sell its protease inhibitors Norvir (ritonavir) and Kaletra (lopinavir/ritonavir) for less than $1,000 each "at no profit" in Africa, and also heavily discount its rapid HIV-1/HIV-2 test, selling it for just $1.20 a kit.

Roche, which had been part of the May 2000 announcement, failed to announce a single discount for a single drug in a single country.

By April, talk was growing of a more systematic, global approach to the problem of providing HIV/AIDS treatment in poor countries. A group of doctors and economists from Harvard issued an ambitious yet well-crafted treatment plan, complete with detailed budget figures, on April 4. Later that month—a week after the Norway meeting—the Rockefeller Foundation cosponsored a meeting on AIDS care in Africa. On April 24, in Abuja, Nigeria, UN Secretary General Kofi Annan issued a call for a $7-10 billion global fund to fight AIDS, tuberculosis, and malaria.

The response was less than encouraging. Many pundits expressed doubt that treatment should be a priority. Public health experts, imbued with a century of prevention-first ideology, were skeptical. Some people who ran prevention programs were worried that they would now compete for dollars against treatment programs. The head of the International AIDS Vaccine Initiative (IAVI) worried that people were forgetting about the need for an HIV vaccine (see accompanying article)—never mind that we didn't have any, nor would we for a decade at least, during which time 100 million people will die if nothing is done.

No one stepped up to the plate. Everyone waited for someone else to take the first step. The silence from the European Union was deafening. Then the new US President announced, with Kofi Annan and Nigerian President Olusegun Obasanjo at his side, that the US—the richest country in the world—was going to provide—$200 million dollars, or 2% of the $10 billion needed. No other country offered so much as a penny.

It's shocking how many people have expressed fear or outrage that HIV treatment has finally been put on the global agenda, as if trying to save the lives of 35 million people—a number certain to pass 100 million long before we have an effective vaccine or otherwise stem the pandemic—is somehow an affront. Maybe to some of them it is an affront, while to others it goes against the grain of the entire 20th century public health ideology which helped to make the global health system into the catastrophe that it is. Just a sampling of some of the more outrageous recent quotes from people who purport to care about global public health:

These kinds of remarks confuse the issue. They are an excuse to keep on doing nothing. What the UN Secretary General actually said in Abuja was:

I propose the creation of a Global Fund, dedicated to the battle against HIV/AIDS and other infectious diseases. This Fund must be structured in such a way as to ensure that it responds to the needs of the affected countries and people... This battle can be won only if we mobilize and focus the efforts of a wide range of stakeholders: national leaders like yourselves, donor governments, the United Nations system, pharmaceutical and other companies, foundations, and voluntary groups—especially those that represent people living with HIV. In other words, we need a complete mobilization of society at large.

Kofi Annan has suggested a $7-10 billion (per year) Global Health Fund to provide a system to prevent, treat, and care for people with HIV/AIDS, tuberculosis, and malaria. This is a credible figure for the first few years. The only detailed math I'm aware of has been done by Harvard (Jeffrey Sachs, Bruce Walker, et al.) in their brilliant "Consensus Statement on ART for AIDS in Poor Countries").

Don't get me wrong—I'm anything but a mindless Harvard booster, having known all too well its smug, often lazy intellectual superiority, its often fake liberal tolerance, its (then) barely disguised horror of homosexuality, and its incestuous old boy networks. However, this time at least, they've done something which no one else has begun to do, which is to quantify the amount that is going to be needed to develop a comprehensive program to prevent, treat, and care for HIV/AIDS in poor countries, (Where was UNAIDS when we needed it?).

AIDS
The Harvard plan is to treat one million people by year 3 and three million by year 5. According to the Harvard economists, $3.3 billion is "a sum that is small in proportion (0.01% of an aggregate GNP of nearly $23 trillion) to the wealth of the donor countries called on to fund this effort." But that's just for Africa. How about the rest of the world? Actually, since Africa accounts for 70% of the world's HIV infected people, it's not that hard to just add 30% to get $4.4 billion.

The biggest hole in the Harvard plan is that it doesn't include funding for viral load and CD4 testing. Nor are the costs of health care worker training and salaries, treatment education and counseling, or the treatment of opportunistic infections addressed. OI prophylaxis, six annual clinic visits and basic blood tests are covered (under the section they label "clinical care," but that's about it.

Admittedly, the Harvard plan does not purport to consider many of these ancillary costs—its focus is antiretroviral treatment—but if anti-HIV drug therapy is to be responsibly administered, these costs will need to be covered by someone, somewhere.

Tuberculosis
One third of the world's population is infected with Mycobacterium tuberculosis (MTB). However, only a small fraction of that number develops clinical tuberculosis (TB) each year. Nonetheless, despite the fact that it is preventable and curable, TB kills over 1.5 million people per year. About 50% of untreated cases die from TB. In 1994, the World Health Organization developed a global strategy for tuberculosis control, dubbed DOTS—Directly-Observed Therapy, Short-course.

From 1995 to 1999, DOTS coverage expanded from 22% of the world's population to 45%, and is now used in 127 of the world's 211 countries. Originally the goal was to have 70% case detection and an 85% treatment success rate by 2005. Unfortunately, despite rapidly expanding global implementation of DOTS for TB, and increasing treatment success, TB incidence is rising. The AIDS epidemic got in the way.

According to the latest figures from the WHO Global Tuberculosis Report for 2001, there were an estimated 8.47 million cases of TB around the world in 1999. Of these, an estimated 3.7 million were smear-positive (they tested positive for acid-fast bacilli (AFB) in their sputum twice, or once in sputum with one confirmatory X ray) and therefore infectious.

TB cases rose by half a million from 1997 to 1999 (from 7.96 million to 8.47 million), mainly because of increasing HIV/AIDS rates in Africa and because of the collapsing public health system in Russia. They rose by 20% in Africa alone.

It's pretty obvious that the HIV pandemic is driving the TB epidemic. WHO estimates that African TB cases will double over the next ten years due to HIV. Cambodia, Myanmar, Thailand and Vietnam accounted for 365 million cases and also have high HIV rates. Other countries on the list, such as India, the Russian Federation, and—most likely—China, now have escalating if not exploding HIV rates. So unless HIV is brought under control in the 22 countries that make up the TB80, all the progress made against TB since the initiation of the DOTS program is likely to be reversed. Thus, it's obvious that providing antiretroviral treatment should be a priority in the TB80. TB care can be integrated into HIV care—and vice versa.

One would think that expanding DOTS coverage to 100% rates in the TB80 would be a very expensive undertaking. But since most of the countries are already implementing DOTS, the WHO estimates that for just $400 million per year (for the next five years) quality medicines and treatment services could be made available to at least 70% of the world's 8 million new TB cases.

Malaria
Almost 300 million clinical cases of malaria occur worldwide each year and over one million people die. Ninety percent of these deaths occur in sub-Saharan Africa, where young children are the most affected. In highly endemic areas adults acquire a degree of immunity through continued exposure, but in areas of less intense transmission and particularly in epidemic areas, most of the population is at risk.

If malaria is diagnosed and treated promptly, the infection may quickly subside. But without effective treatment, severe complications—such as cerebral malaria, severe anemia or multiple organ failure—can rapidly develop,leading to case fatality rates of 10-30%. The progression from mild symptoms to death can be rapid.

The rapid spread of resistance to antimalarial drugs presents a potentially devastating threat to effective treatment. Safe, effective and affordable options are quickly running out, and the discovery of new antimalarials is not keeping pace. Replacement drugs generally last only a few years before they too experience significant resistance. In some areas, such as Brazil and Thailand, only multi-drug therapies are now effective.

WHO estimates that the the annual global cost of halving malaria deaths would be between $375 million and $1.25 billion.

I wrote this piece to find out for myself how much it would cost to save the lives of the 35 million people who are living with AIDS in poor countries around the world. What I found was that they were credible and surprisingly well-founded. What I found—was encouraging. ¤

You couldn't have been much further from the ravages of AIDS than the lovely hotel perched high on a snowy hillside above Norway's largest lake where the meeting was held. At dinner one night a prominent WTO official told me that nothing was better suited than the free market and free trade system to meet "humanity's needs, its hopes, its aspirations." A pharmaceutical consultant darkly warned that price controls were destroying drug company R&D in Europe. The general plan seemed to be to impose a system of differential pricing on the world, with prices secret at all levels, with absolute prohibitions on parallel imports, and with nothing but pro forma protection of countries' rights under the TRIPS agreement. The general philosophy of both the drug companies and the USTR seemed to be that "TRIPS is fine - as long as you don't use it."

On the bus on the way back to the Oslo airport I was talking with the head of Glaxo's entire African program. "Drop the South African lawsuit," I said. "It's not about AIDS," he protested. "I don't care, drop it anyway!" "We can't," he said, uttering all the usual arguments about how if they let South Africa get away with reforming its drug laws, the entire bottom would drop out of the global pharmaceutical market, and R&D worldwide would come shuddering to a halt.

Throughout this entire process, perhaps 5,000 people received discounted AIDS drugs through the Accelerated Access Initiative. Perhaps 5 million new HIV infections occurred, and perhaps 5 million people died of AIDS. Meanwhile, at a glacial rate, additional countries were signing onto the Accelerated Access Initiative - Cameroon, Mali, Rwanda, Senegal, Uganda ... ¤