Important note: Information in this article was accurate in September 2000. The state of the art may have changed since the publication date.
Acquired immune deficiency syndrome is a disease wrought with social, political, and scientific controversies that predate even the naming of the scourge.
HIV has withstood an unprecedented assault of money and scientific talent to tame its nature, remaining unconquered after almost two decades of research.
Its modes of transmission involve the most enduring of taboos. Breaking the cycle of transmission is not as simple as removing the pump handle from a well; fundamental power dynamics within societies must be altered.
And the poor tools that we do have to mitigate the impact of the virus demand massive resources and a global leadership effort if they are to work.
Therefore, it was unrealistic to expect that the XIII International AIDS Conference, held July 9-14, 2000, in Durban, South Africa, would be anything but controversial.
Furthermore, convening in Durban was disquieting for many from the North because it pulled them away from the respite that their wealth has purchased with highly active antiretroviral therapy (HAART). It forced them literally to come face-to-face with some of the 90 percent of HIV-infected people for whom those marvelous advances still have little meaning.
The verbal fireworks that marked the XIII International AIDS Conference had been preceded by ominous media reports on the HIV crisis in the developing world.
UNAIDS released a 135-page report on June 27, 2000, chronicling and projecting forward the devastation of the plague. The death toll has climbed to 18.8 million in only two decades, according to the "Report on the Global HIV/AIDS Epidemic." Last year an estimated 5.4 million people became infected with HIV. The virus continues to spread at an alarming rate in many of the worst hit nations of sub-Saharan Africa.
In seven African nations, one in five citizens carry the virus. A 15-year-old in South Africa stands a 50-50 chance of dying of AIDS by the age of 30, noted UNAIDS Executive Director Peter Piot.
Medical services clearly are overwhelmed by the challenge, but the crisis reaches much further. Disease-weakened adults no longer can plant and tend crops, so production is down and hunger is on the rise. Output from mines and factories likewise suffers. The most socially mobile, those who are skilled and educated, often are hit hardest, compounding the loss to society.
"We have been collectively very wrong," said Piot, assessing earlier projections of how devastating the epidemic would become.
South African President Thabo Mbeki's flirtation with "AIDS denialists" (people who question the link between HIV and AIDS), which has extended to his appointment of a contingent of them to a South African presidential advisory panel on HIV/AIDS, brought much consternation to the international scientific community. (Editor's note: International Association of Physicians in AIDS Care [IAPAC] Trustee William Cameron [University of Ottawa, Canada] represents IAPAC on that panel.)
The response was "The Durban Declaration," a terse 18 paragraphs that summarizes the evidence that HIV causes AIDS; the means by which it is transmitted and hence can be prevented; and the need to develop new, more effective and less expensive therapies for those already infected.
More than 5,000 physicians and researchers working in the field of HIV, including a number of prominent IAPAC members, signed the document before it was published in the July 6, 2000, issue of Nature. A press event scheduled for the opening day of the conference by "Durban Declaration" initiators was canceled at the last moment with no explanation given. Some attendees had argued that it would be an unnecessary affront to their host Mbeki on the day that he was scheduled to deliver the keynote address at the conference's opening ceremony.
On July 9, 2000, several hours before the evening ceremony that opened the conference, demonstrators came together in downtown Durban to demand that pharmaceutical companies make AIDS medications more affordable and that the South African government implement a more effective AIDS plan. Estimates put the crowd at anywhere from 5,000 to 10,000.
Winnie Madikizela-Mandela, former wife of Nelson Mandela, was one of the speakers at the event, which drew conference delegates and activists from around the world. The majority of the protesters were South Africans, seemingly from every social, racial, ethnic, and economic corner of society.
Mbeki's speech that evening was a disappointment to those who had hoped to hear him announce a shift in policy.
"I was hoping and praying that he would find a way to gracefully back out of this madness," Phill Wilson, an AIDS educator from Los Angeles, told the Durban newspaper The Mercury, referring to Mbeki's refusal to clearly acknowledge HIV as the cause of AIDS. "The house is on fire and Mr. Mbeki is sitting around trying to decide whether it was started by a lighter or a match."
"It is important to remember that President Mbeki is not a seminar leader," K enneth Roth, executive director of Human Rights Watch, said at a Durban news conference. "His job is giving the best available scientific information to his people so they can protect themselves. And he is failing miserably at that task."
Even scientist David Ho (Aaron Diamond AIDS Research Center, New York) joined the political commentary on Mbeki's dalliances. "I believe the damage is severe. It is going to delay a national strategy in dealing with this problem," Ho told the same audience. "This is why I took a few minutes to add my voice to that of many others."
Mbeki took another hit at the conference's opening plenary session. The speaker: South African Justice Edwin Cameron, a member of his nation's highest court and one of the most prominent South Africans to speak openly about living with AIDS.
"I exist as a living embodiment of the iniquity of drug availability and access in Africa," said Cameron. "On a continent in which 290 million Africans survive on less than one US dollar a day, I can afford monthly medication costs of about US$400 per month."
Cameron lambasted international agencies, national governments, and the pharmaceutical industry, saying that they "have failed us in the quest for accessible treatment."
The South African government "has at almost every conceivable turn mismanaged the epidemic" so grievously, Cameron said, that since 1998 it has had "the fastest growing HIV epidemic in the world." A "cacophony" of studies, groups, and task forces "all have thus far signified piteously little."
Commenting on the South African government's refusal to mount an effective prevention campaign against mother-to-child transmission, Cameron said, "To our shame ... [every month] 5,000 babies are born, unnecessarily and avoidably, with HIV. Yet we have done nothing."
"One of the important aspects of this meeting is that the concept of even being able to consider therapy in developing countries is on the table and it is being discussed," observed Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID, an agency of the US National Institutes of Health, Bethesda, Md.). "Just a couple of years ago this would have been unimaginable."
In an interview, Pulitzer Prize-winning AIDS journalist Laurie Garrett (Newsday, New York) was even more emphatic, calling the conference "a huge turning point" in the history of the AIDS epidemic. Garrett characterized the conference as being about "access to care, inequity in North-South relations, the whole agenda of how can HAART get to everybody."
Garrett also warned that advocates for greater access to treatment need to step out of the moment to reflect on "how that moment will change history." The search for a short-term good, she cautioned, may "end up creating a long term bad, just as effectively as the drug companies that [the advocates] criticize."
The greatest whispered fear among many people working in AIDS is that widespread use of antivirals under suboptimal conditions or in settings that do not support strict adherence will generate endemic resistance by rapidly mutating HIV. A generation of therapies quickly could be rendered ineffective, not only in the populations that give rise to the mutations but also in other populations at risk for infection.
Yet withholding treatment seems to be inconceivable, not only for ethical reasons, but for pragmatic reasons as well. "We have never claimed that one can control an epidemic by treatment alone, but Medecins Sans Frontieres is now convinced that prevention without any possibility of care is not working," said Eric Goemaere, head of that organization's mission in South Africa. "Why should someone get tested if they have no chance of accessing treatment? Treatment programs will reinvigorate prevention efforts."
The constellation of players--Southern societies and governments, nongovernmental organizations (NGOs), pharmaceutical companies, and Northern societies and governments--seems to be moving into alignment to more effectively confront the global epidemic of AIDS. The question remains: How far and how fast will the players move?
Earlier this year, a significant shift was evidenced by the announcement that five major pharmaceutical companies had agreed in principle to reduce prices. It is important to give credit to the companies for this change, said José M. Zuniga, president of the International Association of Physicians in AIDS Care (IAPAC), in an interview following the conference. At the same time, he noted, "It is important for the community at large to recognize that this movement [on drug pricing] has taken place as a direct result of the pressure that has been applied to the pharmaceutical industry."
Machinations of change played out in the conference's public forums. Some advocates saw generic drugs as a way to slash prices, and compulsory licensing as the weapon to break industry patent control and allow greater production of the more affordable generics.
"Compulsory licensing is something that a society does for the public good," said Eric Sawyer (ACT UP, New York), moderator of a session on the subject. He noted that the US government has imposed compulsory licensing "more than a hundred times over the last few years," primarily in matters related to national defense. Panelist Richard Laing (Boston University) compared it to the legal concept of eminent domain. Both delegates argued that compulsory licensing in developing countries would improve access to therapy.
Jeffrey Sturchio of Merck & Co., Inc. disagreed with their analysis of the problem. He said that most African nations do not have patent laws and therefore are not constrained by existing international treaty. They could have already manufactured generic versions of existing drugs without license, had they so chosen, he said. But they have not, according to Sturchio, because they either lack the necessary industrial/technical capacity to do so or because generic manufacturers do not see the potential for the drugs to be profitable in those markets.
Sturchio used the example of eflornithine, a drug for sleeping sickness. Aventis gave the patent to the World Health Organization (WHO), but WHO has not been able to find a manufacturer that can produce the drug at an affordable price. Sturchio's conclusion is that "compulsory licensing is a much more complex problem than the simple solution would suggest."
Sawyer said that others should follow the lead of Brazil, where the government directs licensed manufacturing for non-commercial use. But Brazil has the eighth-largest economy in the world. Most of the nations hit hardest by AIDS simply do not have the same medical infrastructure and manufacturing capacity that Brazil does.
Local production of a limited repertoire of antiretroviral drugs also invites the risk of creating a vested interest in that formulary at the exclusion of other drugs that may be useful or even superior. A country may be tempted to stick with a regimen because it is produced there, not because it works. Politics and corruption also may restrict local options and the delivery of the drug to patients.
"I think that industry is absolutely prepared to change its view," said outgoing International AIDS Society (IAS) President Mark Wainberg, addressing the topic of drug accessibility in an interview. He pointed to Boehringer Ingelheim's July 7, 2000, announcement that it will offer free nevirapine to resource-limited countries for short course use to reduce mother-to-child transmission (MTCT), "which I don't think that anybody expected."
Free appears to be even better than cheap. So who would refuse such an offer? Many people, as it turns out. The South African government dismissed Boehringer Ingelheim's offer out of hand.
One possible interpretation is that South Africa is looking beyond the short-term scenario of preventing tens of thousands of infants from being born with HIV. Perhaps government officials were thinking of the longer-term scenario of caring for these children when their parents have died of AIDS, which is likely within five years. The specter of AIDS orphans looms large and is growing. How does a nation whose infrastructure and social fabric already are under an enormous stress from HIV disease cope with this added burden?
Surely the pressure would mount to offer treatment to maintain the health of mothers who alone can provide unique nurturing to their children. But can a nation afford that? And if it establishes such a priority, where is the equity for those who are not mothers of young children?
The offer of drugs to reduce MTCT may seem a slippery slope to the Mbeki government and others. Cold-hearted triage--allocating limited resources to those most likely to survive--may be the societal answer that countries with the highest prevalence of HIV infection choose.
"Do we sentence children to death by applying an all-or-nothing principle?" asked IAPAC's Zuniga. "It will require a great deal of political and social courage to address the rationing issue. The sooner South Africans have that public conversation, the better off the nation will be. The longer you defer, the more lives are at stake."
Chris Ouma (Medecins Sans Frontieres, Nairobi) said the Boehringer Ingelheim offer of nevirapine "does not really solve the problem," because drugs need to be made available in a sustainable manner over a longer period of time.
While Ouma admitted that the existing healthcare infrastructure is inadequate to sustain such a program, he still called for the immediate implementation of mother-to-child transmission programs. Ouma expressed hope that if cheaper generic drugs become available, governments of developing nations will become more willing to invest in creating the necessary healthcare infrastructure.
Wainberg saw that infrastructure as the greatest goal, one "that we have to strive to procure." He said that he is encouraged by recent initiatives that focus on strengthening medical infrastructure, including Secure the Future, funded by Bristol-Myers Squibb, and a Botswanan program supported by Merck and the Bill & Melinda Gates Foundation. (See sidebar, left, for more information.)
"When we chose South Africa, many, many expressed their concerns, particularly those who are not with us today," said Stefano Vella, incoming president of IAS, at the closing ceremony on July 14, 2000. "But this conference proved that they were wrong."
"We picked Durban. We did not turn our backs on Africa," said Wainberg, who chaired the committee that chose the site. "We recognize that these meetings always have a double function. One is to stimulate research, but the other is to stimulate HIV awareness and education."
Zuniga said that the conference location "served to magnify the inequities that exist in access to the very medications that we are celebrating in the North." It also offered a unique opportunity for service providers to network in the heart of the epidemic, he observed. "I think that we are going to see a number of key partnerships come out of this conference."
"Despite all of the protestation and fears and recriminations and boycotts, despite all of that, we had 12,456 people attend this conference," announced South African pediatrician Hoosen Coovadia, chair of the conference, at the closing ceremony. More than a third of the delegates were from Africa. "It is probably a watershed meeting for developing countries and may be even an historic meeting for the world," Coovadia said.
"To all of you who ignored the threats, the boycotts, the criticisms, the fears, and had the courage and the solidarity as you did when you fought against apartheid, you had the solidarity to be with us. My colleagues and I are eternally grateful.
"Some magical ingredient of time, place, and people in this city in South Africa have managed to create a mood and a tone of liveliness bordering on exhilaration," Coovadia added. "I think that it is an exhilaration arising from hope."
Former South African President Nelson Mandela, whom many South Africans regard as their greatest national hero, entered the massive closing session to a sustained standing ovation, complete with cries in Zulu and chants from the struggle against apartheid.
He looked frail but his ringing voice belied his 82 years and offered a capstone of hope that the attendees had been seeking. "If 27 years in prison have done anything to us," said Mandela, "it was to use the silence of solitude to make us understand how precious words are and how real speech is in its impact upon the way people live or die."
Mandela praised Mbeki several times during the course of his speech. He did not dwell on Mbeki's embrace of the AIDS denialists or on other controversies that had dominated discussion and news coverage of the conference. Instead, he called those controversies a distraction "from the real life and death issues."
"In all disputes a point is arrived at where no party, no matter how right or wrong it might have been at the start of that dispute, will any longer be totally in the right or totally in the wrong," he said. "Such a point, I believe, has been reached in this debate."
"The ordinary people [and especially] the poor who bear a disproportionate burden of this scourge," Mandela said, "... wish that the dispute about the primacy of politics or science be put on the back burner and that we proceed to address the needs and concerns of those suffering and dying. And this can only be done in a partnership."
He called upon the tradition of collective leadership in Africa. "In the face of the grave threat posed by HIV/AIDS, we have to rise above our differences and combine our efforts to save our people," he said. "History will judge us harshly if we fail to do so now, and right now."
Mandela outlined the need for programs that work to "banish stigma and discrimination," prevent new infections, offer treatment, and support the survivors. His call for "measures to reduce mother-to-child transmission" generated one of the many bursts of applause that punctuated his address.
While acknowledging the need for support and for alliances, Mandela cautioned that "others will not save us if we do not primarily commit ourselves." He concluded, "Let us combine our efforts to ensure a future for our children."
Halting the AIDS pandemic in Africa and other resource-poor areas of the world will take more than a cache of discounted antiretroviral drugs. It will require a framework that joins healthcare provider and patient education, distribution systems, medications, political will, and private sector support. In other words, an infrastructure. As the XIII International AIDS Conference came to a close in Durban, South Africa, experts expressed optimism about a number of new or recent initiatives aimed at creating that infrastructure. They include:
--Rebecca Voelker
A July 13, 2000, debate at the XIII International AIDS Conference focused on whether tuberculosis (TB) prophylaxis should be given to all HIV-infected persons in resource-limited, high-TB-incidence settings. The argument centered on the value of tuberculin skin tests and the relative merits of early versus late intervention. TB is now the leading cause of death for HIV-infected people in many developing countries.
For blanket prophylaxis
Alwyn Mwinga (University Teaching Hospital, Lusaka, Zambia) presented the case for TB prophylaxis for HIV-infected people in resource-limited settings. She quoted World Health Organization (WHO) statistics estimating 10 million cases of TB worldwide in 2000, 1.4 million of which are attributed to coinfection with HIV. "HIV is the strongest risk factor for reactivation of latent TB infection," said Mwinga. "Thus a role for prophylactic TB treatment has been suggested again in developing countries."
Izoniazid has been used to treat latent TB infection since 1995, Mwinga reminded the audience. The efficacy of izoniazid prophylaxis in HIV-uninfected people is 60 to 90 percent, she said. Preventive treatment is usually part of TB control strategies in countries with lower TB burdens.
Screening identifies individuals with latent TB. But Mwinga cautioned that the tuberculin skin test lacks specificity for TB, is unable to distinguish between disease and prior vaccination, and has even less utility in detecting TB in HIV-infected persons. She cited studies showing that, although TB prophylaxis for skin-test positive persons yields more protectivity, some protectivity has also been seen in skin-test negative patients.
"In countries with low rates of transmission, we should use the tuberculin skin test," she said. "In high TB burden countries, the tuberculin skin test should not be used as part of a screening procedure, and all HIV-infected persons without active TB should get prophylactic therapy." Mwinga based her argument partly on logistical issues: the need for trained staff to administer and read the test, the extra visit required to the clinic to read the test, the need for refrigerated storage of the tuberculin, and a low shelf life once the tuberculin vial has been opened.
"However," she said, "the necessity to exclude active TB cannot be overstated, due to the risk of increasing drug resistance." This, she acknowledged, brings up more logistical issues involving cost and equipment. Nonetheless, Mwinga recommended TB prophylaxis as part of a minimum package of care for HIV-infected people in resource-limited, high-TB-incidence settings. She suggested the possibility of offering prophylaxis in counseling and testing settings rather than clinics, since the treatment would be more effective in earlier stages of HIV disease.
Mwinga acknowledged her debate opponent's point that the protective effect of prophylaxis is limited to only about 18 months, but she encouraged participants to look at the issue from the perspective of a person with HIV. "I think if I had HIV, I would feel like you were giving me two years or two-and-a-half years to be productive and take care of my family."
Against prophylaxis without skin test screening
The case made by Gary Maartens (University of Cape Town, South Africa) against providing TB preventive therapy to HIV-infected persons in high-TB-incidence areas rested on two assertions: that individuals at risk can be identified, and that preventive therapy is "not terribly effective in preventing TB."
"This is not a terribly powerful intervention," Maartens said, arguing that estimates of a 60 percent reduction rate as a result of preventive therapy might be high.
Maartens compared costs of tuberculin skin testing to preventive therapy, asserting that prophylaxis--with six clinic visits for directly observed therapy--is not cost-saving. "And I would argue that the person who doesn't return for their [tuberculin skin] test [results] isn't really the kind of person who will stick with six months of [prophylactic] therapy," he added.
Maartens quoted results of a study he conducted in the South African Cape. The most powerful predictor for acquiring TB in this study was advanced HIV infection (WHO stages III or IV). "More research is needed," said Maartens. "This may warrant the use of preventive therapy [in people with advanced HIV disease] regardless of [skin test] status."
A major point of contention in the Durban debate was Maarten's focus on treating people in advanced stages of HIV infection, as opposed to Mwinga's concern for intervening in the early stages of the disease. Maartens responded to Mwinga's concerns about the relative difficulty of screening for TB in people with later-stage HIV, saying, "It is more difficult, but not impossible to screen for TB in late stages of HIV." He asserted that correct diagnoses could be made based on sputum testing and symptomology.
Maartens advocated increased screening because, in his opinion, tuberculin skin testing helps determine who might actually benefit from preventive therapy. "The key to success [with TB control programs] is to bump up cure rates," he concluded, estimating current cure rates in Africa to be about 60 percent, and suggesting a target goal of 85 percent.
--Carmen Retzlaff
Bob Roehr is a medical writer based in Washington, DC (BobRoehr@aol.com).
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