The first 25 years of the global HIV/AIDS pandemic produced a massive global mobilization of affected communities at an unprecedented level. AIDS activists, service organizations, support groups, and networks of treatment activists made history by accelerating the response to AIDS and stimulating public awareness and support, contributions of government resources, scientific investment, concern for legal and civil rights, protection from discrimination, and the formation of new local, national, and global institutions to respond to the disease.
AIDS activism has taken very different forms, depending on the shape of the epidemic, the political context, civil society mobilization, economic resources, scientific research, and the international response. Activist strategies and tactics included linking activism with education and information as well as use of the mass media, mobilization via the World Wide Web, political lawsuits and legislation, direct action (including public demonstrations and civil disobedience), and a variety of different coalition-building strategies.
The first activist and self-help groups for people with AIDS (PWA) formed even before the discovery of the HIV in 1983. They focused on giving a face and a voice to people with AIDS and demanded meaningful participation within all organizations with power over their lives. Effective AIDS activism built on a foundation of strong community service and support organizations such as Gay Men's Health Crisis, formed in 1982, and self-empowerment groups such as the PWA Coalitions in many cities around the United States.
One of AIDS activism's historical contributions to the history of the HIV pandemic has been its relentless pressure, and ultimate success, in pushing for increased, accelerated AIDS research, particularly to discover, develop, rapidly approve, and broadly distribute effective treatments for HIV and related conditions. Here activist pressure produced historic results. It is likely that without activism, the development of effective preventive and therapeutic treatments for AIDS-related opportunistic infections would have been slower and less coordinated and that the research that led in 1996 to the introduction of potent combination antiretroviral therapy (ART) would have taken place much more slowly, or in the absence of a more flexible regulatory environment-also created in response to activist pressure-not at all. Without these breakthroughs in treatment, AIDS deaths in the United States would have kept on climbing from their peak of 50,000 in 1994. Hundreds of thousands of people now living would have died. And failure to develop potent combination ART would have precluded or at least greatly delayed the post-1996 mobilization for global treatment access.
The AIDS Coalition to Unleash Power (ACT UP) and allied groups such as San Francisco's Project Inform created cadres of activist experts in research and treatment. Through national demonstrations at the Food and Drug Administration (FDA) in 1988, and through follow-up activism and negotiations, ACT UP and its allies forced the FDA to speed up the development and approval of new AIDS drugs.
Starting in 1989, the FDA also allowed broad preapproval access (“parallel track”) to experimental AIDS drugs for people with AIDS lacking other treatment options. Between 1989 and the approval of the nucleoside analogue didanosine (ddI) in 1991, the first parallel track program provided this drug to more than 35,000 people with HIV who were failing or could not tolerate zidovudine (AZT), the first approved anti-HIV drug.
In 1990, ACT UP demonstrated at the National Institutes of Health (NIH), successfully demanding the inclusion of PWAs and their advocates in the research programs and protocols carried out with NIH support by the AIDS Clinical Trials Group and other networks. This led to the formation of national and local community advisory boards within the AIDS Clinical Trials Group and other NIH-funded clinical trials networks. Unprecedented in the history of medical research, these community advisory boards and related structures provided people with HIV and their advocates with a concrete role in the design, implementation, and evaluation of clinical trials.
Treatment activists and people with AIDS put forward an ambitious research agenda that called for the codification of parallel track, implementation of accelerated approval, the removal of obsolete restrictions on study entry criteria, the inclusion of all affected or infected groups-for example, women and drug users-in clinical trials, and for studies of interventions to prevent and treat HIV's opportunistic infections and cancers, not only for studies focused solely on anti-HIV therapy.
In 1991, ddI became the first drug to be approved under the accelerated approval mechanism, which was codified by the FDA in 1992 and which allowed drugs to be licensed based on preliminary evidence using surrogate markers for clinical efficacy. The first crop of anti-HIV drugs following AZT-ddI, zalcitabine, and stavudine-were licensed based on early positive increases in CD4 counts among those on the experimental drug compared with the control group (usually on AZT). Because CD4 counts were a reflection of an individual's stage of immune deficiency rather than a direct indication of the drug's activity, CD4 counts were only an indirect measure of HIV treatment efficacy. During the mid-1990s, however, several companies developed sensitive, quantitative tests that measured the amount of HIV nucleic acid (viral load) in the peripheral blood. These sensitive viral load assays, which were introduced along with highly active antiretroviral therapy (HAART) during the mid-1990s, enabled much more precise measurement of anti-HIV drug activity, at the individual patient level, in clinical trials, and as surrogate markers for accelerated regulatory approval. During the early 1990s, ACT UP produced a number of more specialized organizations focusing on areas such as needle exchange, housing for homeless PWAs, and research advocacy. The Treatment Action Group was formed in 1992 to focus exclusively on AIDS research and treatment advocacy. With the start of the Clinton administration in 1993, Congress passed a law including provisions developed by Treatment Action Group to strengthen the AIDS research effort at the NIH and its Office of AIDS Research. Over the next decade, the AIDS research budget at NIH grew to more than a billion dollars per year.
Accelerating drug approval, increasing research funding, and a new focus on basic research helped produce a clinical breakthrough in 1996 with the simultaneous introduction of sensitive quantitative viral load testing, potent HIV protease inhibitor drugs, and 3-drug combination therapy introduced together to forestall the development of drug resistance.
With the introduction of HAART in 1996, US AIDS deaths began a sharp decline after peaking at 50,000 deaths per year in 1994 and 1995, stabilizing at about 17,500 deaths annually at the turn of the millennium.1,2
Progress in anti-HIV therapy was paralleled by a series of studies that provided a new standard of care to prevent the most common opportunistic infections among people with HIV, including disseminated cytomegalovirus disease, disseminated fungal infections, Pneumocystis pneumonia, and toxoplasmosis. With the introduction of HAART, the incidence of several HIV-associated cancers, including Kaposi sarcoma and non-Hodgkins lymphoma, also decreased during the 1990s.
Treatment activists also influenced the research carried out by the pharmaceutical industry and that sponsored by the NIH. By the mid-1990s, it was common for each new HIV drug sponsor to consult extensively with community activists when experimental treatments entered phase II trials. Much of the interaction concerned study designs, the timing of expanded access, and inclusion criteria. After the HAART revolution, activists focused new attention on long-term effectiveness research (so-called strategy trials), reducing side effects, improving options for salvage therapy, and assessing whether so-called structured treatment interruptions would result in improved outcomes for people on ART. One of the key studies to emerge from this advocacy was the NIH-sponsored Strategic Management of ART study, one of the few studies with clinical endpoints conducted in the HAART era, which not only demonstrated that CD4-guided therapy interruptions were dangerous compared with constant treatment but also introduced a new set of research questions by demonstrating that much of the so-called non-AIDS endpoints once thought to be related to HIV treatment seemed in fact to be sequelae of HIV infection itself.
As these studies were being carried out and a raft of new drugs, fixed-dose combinations, and new drug classes such as entry inhibitors, CCR5 receptor blockers, and integrase inhibitors entered the pipeline and eventually received FDA approval, some treatment activists turned their attention to strengthening the world's response to the global side of the HIV pandemic, where 95% of those infected lived; in 2003, fewer than 100,000 HIV-positive people living in developing countries were receiving ART, and most of those lived in Brazil, the only developing country to provide universal access to ART during the 1990s.
In the early 2000s, a confluence of events led to an unprecedented scale-up of ART programs in developing countries. There were multiple actors, and several new institutions and programs were established to carry out this work, including the Global Fund to Fight AIDS, Tuberculosis and Malaria (beginning in 2002), the President's Emergency Plan for AIDS Relief (2003), the 3 × 5 initiative of the World Health Organization (WHO, 2002-2005), and UNITAID (initiated in 2005).
US-based activists joined with a variety of groups from around the world to establish coalitions to advocate for faster ART scale-up and to educate each other on HIV treatments. One such coalition, the International Treatment Preparedness Coalition, was established in 2003 and has joined forces with a variety of funders to support HIV treatment literacy among hundreds of community-based organizations around the world.
These activist groups did not recapitulate the model of treatment activism developed in the United States but developed their own advocacy networks and strategies based on their own national experiences and needs. Locally based activism was an essential part in the dramatic scale-up of access to ART, which led to at least 4 million HIV-infected persons being treated with ART by the end of 2008.
The situation was quite different with the coinfection that infected more than one-third of the world's population and was the leading cause of death among people with HIV-tuberculosis (TB). An age-old disease, TB was discovered in 1882 by Robert Koch, who developed the 2 most common diagnostic tests used for the disease (sputum smear microscopy) and the infection (tuberculin skin testing). A partially effective vaccine, the Bacille Calmette-Guérin, was developed between 1908 and 1921 and is given to 100 million babies each year. However, it prevents only about 55,000 deaths, primarily from disseminated (miliary) TB and tuberculous meningitis, and does not protect against infection with TB nor against pulmonary disease in adolescents and adults. Chemotherapy with antituberculous agents, pioneered in 1948, resulted by the late 1970s in a 6-month curative regimen consisting of 4 drugs given for 2 months followed by 2 drugs given for 4 months.
TB was thought to be on the decline globally until the 1980s when, driven by HIV, it resurged dramatically around the world. A 1989-1991 outbreak in New York City of TB that was multidrug resistant (MDR), principally associated with the HIV pandemic, led to a resurgence of global activity against TB. The public health establishment succeeded in controlling this MDR-TB outbreak using a combination of directly observed therapy, short course (DOTS); isolation; and at times involuntary detention of infectious, nonadherent individuals. The cost of this-more than US $1 billion-led the US government to expand support for its TB program domestically. TB research was reestablished at the NIH after nearly coming to a complete halt. Globally, the WHO declared TB an emergency in 1993 and adopted the DOTS model. Later, it developed a worldwide coalition of groups, the Stop TB Partnership, to promote DOTS uptake. The HIV pandemic accelerated the spread of TB, especially in sub-Saharan Africa and in the newly independent former Soviet states, where the collapse of the public health system was accompanied by an alarming spread of MDR-TB.
During the late 1990s, WHO resisted treating MDR-TB patients, claiming that DOTS alone would reduce the incidence of MDR-TB. In much of the world, however, because of inadequate delivery systems, the lack of patient education about adherence and resistance, and incomplete treatment courses, MDR-TB continued to emerge and eventually spread from person to person and by 2006 was observed to have progressed to an outbreak of so-called extensively drug-resistant TB in an HIV treatment program in KwaZulu-Natal province, South Africa.
Clearly, HIV treatment activists needed to address TB, the most common cause of death among people with HIV and also a continuing one even after ART initiation. Concerted activism against TB began in 2002 at the World Conference on Lung Health in Montreal, Canada, where a few HIV activists from Brazil, the United States, and Zambia began to focus on the threat that TB represented to people with HIV. By 2005, the activists had persuaded the Stop TB Partnership to include community representatives on its Coordinating Group and its working groups, including groups focused on TB/HIV, MDR-TB, and the development of new drugs, new diagnostics, and new vaccines to better control TB.
Starting in 2004, Treatment Action Group partnered with the Open Society Institute to train a series of cadres of HIV treatment activists in TB science, policy, and treatment literacy, with a global focus and with special attention to sub-Saharan Africa. Once again, as TB research emerged from the glacial state in which it had languished for decades, HIV community treatment activists began to get involved with sponsors of new TB treatments and vaccines, with a special focus on diagnostics, because smear microscopy diagnosed only 19% of cases worldwide and because most people with HIV presented with smear-negative or extrapulmonary disease.
By mid-2009, the TB research scene resembled HIV research of the late 1980s, with a few new drugs entering phase II studies, but with inadequate support for research at all levels, and with a clear need for greater community pressure on funding agencies and high-burden countries to tackle the TB problem at the required scale. TB still kills more than 2 million people a year, almost as many as HIV, yet for every dollar the NIH spends on HIV research, it spends just 5 cents on TB research. Similar underfunding is apparent in the private sector. The only major non-NIH funder of TB research is the Bill & Melinda Gates Foundation, which supports a series of product-development partnerships, such as the Aeras Global TB Vaccine Foundation, the Foundation for Innovative New Diagnostics, and the Global Alliance for TB Drug Development.
Currently, 6 experimental TB drugs, 5 of them in new therapeutic classes, are in phase 1 and 2 studies. Several new TB vaccine candidates are slated to enter phase 2 in the near future. Molecular diagnostics are beginning to be introduced in developing countries and have the promise to speed up TB diagnosis where sophisticated laboratories capable of carrying out DNA analysis exist. Nonetheless, it has been only during the past 5 years that the world has admitted that we do not have the tools to control TB (a change from the 1990s and the early 2000s, when the Stop TB Partnership claimed, that “we have the tools to stop TB”). Given the resurgence of TB, its deadly synergy with HIV, and the continuing evolution of ever-more-resistant strains, it will be essential for community activists to be vigilant in promoting and in monitoring TB research and TB programs worldwide.
In mid-2009, the world's responses to HIV and TB are challenged by a global recession, a global health architecture in disarray, and a backlash against AIDS funding (drawing TB in its wake, even though, as noted above, TB receives far fewer resources). Community treatment activism, which has played such a vital role in accelerating research on HIV and in promoting universal access to HIV treatment, will have to expand and sustain itself to meet the challenges posed by HIV and TB as we enter the fourth decade of the HIV pandemic.
Yet, there are signs of hope. The very scale-up of HIV and TB collaborative activities that has taken place since WHO issued its recommendations in 2004 has been impressive. A number of countries have reached almost universal voluntary HIV testing among their TB patients. This has resulted in the discovery that, at least in sub-Saharan Africa, many more TB cases were HIV-positive than previously believed; the WHO raised its estimate of annual TB incidence among HIV-infected people to about 1.4 million cases per year. More importantly, this discovery helped link HIV-infected TB patients with HIV services, including ART when needed.
Other results of scale-up of HIV/TB collaborative activities include the beginning of more focus on infection control, such as the scale-up of improved airborne infection control in HIV, TB, and primary care clinics that is taking place currently in the wake of the extensively drug-resistant TB outbreak in KwaZulu-Natal province, and the scale-up of laboratory capacity-for TB microscopy, rapid TB culture, and TB DNA testing for drug resistance, which in some places is being carried out in laboratories that are already doing HIV DNA testing to detect HIV infection among neonates. Linking the very different cultures of TB control and HIV universal access has been difficult, but the evidence for benefit at an individual and population level is growing. Indeed, a recent article from the Desmond Tutu Centre at the University of Cape Town indicated that alongside the scale-up of HIV treatment from 2003 to 2008 in a peri-urban township in Western Cape Province, the incidence of TB among people with HIV dropped by almost 80%-one of the first indications that scale-up of HIV treatment where TB services are adequate can result in reductions in TB burden at a population level.3 The integration of TB and HIV collaborative activities exemplifies the ways in which scale-up of programs for the 2 diseases can result in health system strengthening and reduce the seemingly inexorable increase in TB seen since the early 1990s. Although the cultures of HIV and TB control remain distinct, the sectors work together in better harmony and awareness than before. It was necessary to link programs, training, staff, laboratories, surveillance, case records, and patient care in an unprecedented way.
Dr. Anthony Harries, who worked extensively in Malawi in the national TB and HIV programs, recently noted that Malawi, although it had outstanding HIV and TB programs, was among the worst-performing countries when it came to maternal mortality, second only to the Democratic Republic of the Congo. He described the differences that drove this disparity as simply the fact that in the TB and the HIV programs, there was quarterly recording and reporting of patient status and outcomes, and there were no stockouts of drugs, test kits, and other vital commodities; by contrast, the primary care and maternal-child health systems suffered from inadequate recording and reporting and frequent stockouts of vital commodities and treatments.
In this way, implementation of the collaborative TB/HIV activities has useful and encouraging lessons for scaling up high-quality universal access to comprehensive primary care that includes prevention and treatment of priority diseases-and illuminates the fact that scaling up disease-specific programs has spin-off benefits that strengthen the health system as a whole. What is needed is the political will and financial and technical support to enable countries to fully scale up their health systems for all people in need.