Book Review

The Search for an AIDS Vaccine and an Effective Global Response

Shots in the Dark: The Wayward Search for an AIDS Vaccine

N Engl J Med 2001; 344:1801-1802June 7, 2001

Article

Shots in the Dark: The Wayward Search for an AIDS Vaccine
By Jon Cohen. 440 pp. New York, W.W. Norton, 2001. $27.95. ISBN: 0-393-05027-0

In 1984 — 17 years ago — Health and Human Services secretary Margaret Heckler announced that an AIDS vaccine would be ready for testing in 2 years. Since then, nearly 60 million persons worldwide have been infected by the human immunodeficiency virus (HIV), and only one vaccine, containing the gp120 surface protein of the virus, has made it to a large-scale, phase 3 efficacy field trial. Jon Cohen's book Shots in the Dark explains the reasons for this intolerably slow progress, despite the great advances that have been made in biotechnology, genetics, and immunology.

Cohen believes that a major obstacle to the successful development of a vaccine has been the domination of the field by “reductionists” (mostly virologists) who are interested primarily in understanding the pathogenesis of HIV infection and the interaction of the virus with the immune system. One consequence of this domination was the early focus on the production of antibodies against the virus, which delayed the recognition of the importance of cell-mediated immunity in protection against HIV infection. An empirical, targeted approach to the development of a vaccine was defeated, primarily because of fears that it would encourage mediocre science and deplete resources for basic research. The argument that more needed to be known about HIV and the immune response to it before a targeted program could be designed always prevailed.

Cohen cites other obstacles. These include a lack of interest on the part of major pharmaceutical companies in developing an AIDS vaccine because of concern about liability and profit; disagreements about the relevance and importance of animal models; differing views regarding what a vaccine could achieve (prevention of infection vs. protection of the already-infected from disease); ethical problems related to the design of placebo-controlled trials and the treatment of vaccinated persons who became infected during the trials; and the limited interest among industrialized countries in supporting vaccine research.

Cohen argues that this wayward search for an AIDS vaccine could have been avoided through the centralization of leadership and the unification of direction from the outset, along the lines of the March of Dimes model that was so successful in the development of a poliovirus vaccine. Such leadership would have designed a master strategy to deal with the obstacles to vaccine development, rigorously compare vaccine strategies, and follow up promising leads. The National Institutes of Health (NIH) could not provide this leadership, because of its esteem for investigator-initiated science and its disdain for directed research. What Cohen feels is needed now is a $1 billion program — he calls it the March of Dollars — that would be privately administered by someone with a deep personal and moral commitment to the development of a vaccine, under whom a scientific director would oversee two scientific boards. One board would fund urgent basic research, and the other would support the production and testing of candidate vaccines. Cohen is impressed with the bold initiatives taken by the International AIDS Vaccine Initiative, recent changes in the NIH's vaccine program emanating from its comprehensive review by the Office of AIDS Research in 1996 (often referred to as the Levine Committee report), including the establishment of a Vaccine Research Center, and the formation of the activist-led AIDS Vaccine Advocacy Coalition, but he still believes that the program he advocates will substantially improve the chances for the rapid development of an effective vaccine.

Unfortunately, the failure to mobilize the international scientific community to develop a safe and effective AIDS vaccine exemplifies the worldwide response to the epidemic itself. In May 1987, the World Health Assembly in Geneva endorsed a Global AIDS Strategy to prevent and control AIDS. The strategy was meant as a practical framework to encourage common policies; it was to be an evolving vision of what was required to confront the epidemic and a metaphor for global solidarity. Most developing countries (where 95 percent of HIV infections have occurred) soon formulated national AIDS-control programs, primarily with the technical guidance of the World Health Organization's Global Program on AIDS (I was the director of that program from 1990 to 1995), and there was moderate success in some areas. These included a greater awareness of the importance of protecting the human rights and dignity of persons living with HIV or AIDS; the restoration of confidence in blood-transfusion services; the establishment of voluntary HIV-testing and counseling centers; the recognition of the importance of early treatment for sexually transmitted diseases in preventing the transmission of HIV (particularly during early stages of the epidemic); the implementation of a continuum of care, ranging from basic home care to affordable treatment of opportunistic infections, particularly tuberculosis; and the active involvement in control efforts of nongovernmental organizations and networks of persons with AIDS.

In a few countries — notably Uganda, Senegal, Zambia, Thailand, and Cambodia — prevention achieved considerable success. However, the response to the epidemic in many other countries was delayed, insufficient, or inappropriate. As a result, the number of HIV infections rose from 6 million in 1990 to more than 20 million in 1995 and nearly 60 million today. The reasons for this inadequate response are complex. As a sexually transmitted disease, AIDS often engendered moralistic responses rather than effective public health action; its association with stigmatized and marginalized groups and its presumed lethality were also important factors. In addition, the international community was unable to muster a coordinated, unified response, because of territoriality among international and bilateral donor agencies. Finally, industrialized countries had become complacent because of the mistaken belief that heterosexual transmission was uncommon and that persons with HIV disease could live for many years or even be cured through the use of combination therapy with antiretroviral drugs.

The turn of the century has witnessed a dramatic increase in awareness of the pandemic, primarily because of global concern about equity in access to antiretroviral drugs in low- and middle-income countries. The threat of importation and local production of generic drugs has reduced the cost of combination therapy to around $600 per year in African countries. Brazil's AIDS program, which has made antiretroviral drugs available to the public since the mid-1990s, reports much success in preventing deaths due to AIDS and new HIV infections (by decreasing viral load) and is considered by many to be a model for the developing world. In addition, a structure is now in place (the Joint United Nations Program on HIV/AIDS, or UNAIDS) to coordinate, monitor, and evaluate the international response to AIDS.

Tragically, it has taken nearly 25 million deaths from AIDS and the near-devastation of the social fabric of many African nations to raise worldwide consciousness. Nevertheless, we must exploit this opportunity, since it may not occur again. We must strengthen the infrastructure of fragile health systems so that antiretroviral drugs can be given safely and effectively. Training of health care providers, improvement of laboratories and counseling services, and better logistic and monitoring systems are essential. There are demonstrated increases in high-risk sexual behavior and in the risk of sexually transmitted diseases among those receiving antiretroviral treatment. It seems that unsafe sexual behavior is a greater threat than drug resistance to the efficacy of antiretroviral drugs. It is thus essential that prevention be an integral component of care for the infected.

We must give prevention the same attention and support now being directed toward care. Social and behavioral research during the past 15 years has demonstrated the efficacy of a wide range of community-based prevention efforts. HIV prevention is relatively inexpensive and highly cost effective, but to be most effective it must be supported by legal and social policy reforms.

The few AIDS-related success stories have one common characteristic — strong political leadership. Later this month, the United Nations General Assembly will convene a special session on AIDS that will provide an opportunity for heads of state to demonstrate such leadership. An appeal will be made for rich nations to contribute billions of dollars to a global AIDS fund to support programs that will prevent HIV infection among vulnerable populations, ensure full access to care and antiretroviral drugs, and develop an effective AIDS vaccine — an area in which much progress has recently been reported in evoking cellular immunity specific to HIV. The U.S. government must be in the forefront of leadership. It is too late to reverse the severe consequences of this pandemic in Africa and elsewhere, but there is still much that can be done to alleviate the suffering of more than 36 million persons now living with HIV and to prevent millions of new infections in Africa, as well as in South and Southeast Asia and eastern Europe, where a scenario resembling that of Africa is waiting to unfold.

Michael Merson, M.D.
Yale University School of Medicine, New Haven, CT 06520-8034

Citing Articles (2)

Citing Articles

1. 1

   John E. Calfee, Roger Bate. (2004) Pharmaceuticals and the Worldwide HIV Epidemic: Can a Stakeholder Model Work?. Journal of Public Policy & Marketing 23:2, 140-152
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2. 2

   Steinbrook, Robert, Drazen, Jeffrey M., . (2001) AIDS — Will the Next 20 Years Be Different?. New England Journal of Medicine 344:23, 1781-1782
   Full Text