Experts offer mixed view of HIV vaccine's future
AIDS Healthcare Foundation (AHF) of Los Angeles recently raised a stir when the organization's president and its medical chief announced that it was time for the federal government to stop funding research for the HIV vaccine and to put that money into prevention and treatment that works.
The HIV/AIDS advocacy group's announcement follows on the heels of repeated disappointments in the HIV vaccine research arena. None of the Phase III clinical trials have held any possibility of hope thus far.
Some major newspaper editorials disagreed with AHF, including those in The New York Times and the Los Angeles Times, saying HIV vaccine research is necessary and should continue to be publicly funded. At the very least, AHF succeeded in making HIV vaccine funding more controversial. "I think we're providing a great public service by saying the emperor has no clothes and HIV vaccine funding needs to be reconsidered," says Michael Weinstein, AHF president.
"The greatest minds in the field" already have said an AIDS vaccine will be decades away or not at all, Weinstein says. "I think it's irresponsible to not have a dialogue in the debate over the worthiness of funding this vaccine," he says. "In terms of some of the responses I've gotten, I feel like we're arguing over religion, not science."
So far, there has been 25 years of HIV vaccine research, and the U.S. government has spent more than $850 million on the research, Weinstein says. "At the beginning of this epidemic, the idea that we could take a shot at a vaccine and, like polio, protect everybody was very [appealing]," Weinstein says. "But we didn't anticipate that we'd have a cocktail that would keep people alive and well for decades and render them noninfectious."
Homayoon Khanlou, MD, chief of medicine for AHF, says, "If we were able to obtain a vaccine, we should have had it by now. The fact that we don't have it means there's something about the virus that defies our knowledge."
So far, all of the clinical trials done with the HIV vaccine have yielded no results, and they have given scientists no clues about which direction to go next, Khanlou adds.
Is it premature to dismiss AIDS vaccine?
Some scientists say AHF is premature in dismissing the possibility of an AIDS vaccine.
"I think this issue has had recent publicity because of the failure of the Merck trial, but in reality the issues confronting an HIV vaccine have always been huge," says Sarah Rowland-Jones, BM, BCh, MA, DM, FRCP, director of research at the Medical Research Council Laboratories of The Gambia, West Africa.
"With the exception of rabies, virtually all our successful vaccines are based on the simple principle that if a person survives the initial encounter with a pathogen, this is usually followed by lifelong immunity," Rowland-Jones says. "This is not the case with HIV-1."
Also, the most successful vaccines have employed killed or attenuated organisms, she notes. "These approaches appear to be successful against SIV in animal models, but the risks inherent in developing these approaches for an HIV-1 vaccine have, so far, discouraged any commercial development of these routes," Rowland-Jones says.
A third factor that makes development of an HIV vaccine so difficult is that there have been no successful vaccines against an organism that is as inherently variable as HIV-1, Rowland-Jones adds.
Some encouraging signs
While vaccine critics have focused on Merck's STEP trial, there are encouraging signs that new generations of HIV vaccines are inducing better and qualitatively different immune responses than what was included in the Merck HIV vaccine, says Shan Lu, MD, PhD, professor of medicine at the University of Massachusetts Medical School in Worcester, MA. Lu specifically refers to the 2008 Phase I vaccine study published in the Journal of Experimental Medicine and the recent Phase I vaccine study in Vaccine.1,2
The EuroVacc 02 Phase I trial had promising immunogenic results with T cell responses in 90% of vaccinees.1 The DP6-001 Phase I clinical trial showed robust cross-subtype HIV-1 specific T cell responses in IFNgamma ELISPOT assays,2 but those are very early results and might never make it to phase III clinical trials.
"My chief concern in 2008 is the possibility of a complete or close to complete stop in HIV vaccine development," Lu says. "My broad concern is that vaccinology, as a specialized area in biomedical science, has been ignored or neglected at least for a big part of the last 20 years. The current sentiment to stop funding for HIV vaccine research is part of this continued ignorance."
While it's true that there are many diseases affecting the developing world that have been ignored by vaccine funders, this is not the case with HIV vaccine research, Weinstein says. "We've spent tens of billions of dollars on HIV vaccine research, and we have had no results," he says. "Also, a lot of money is being spent to maintain networks of people on whom a vaccine should be tried. This is completely unnecessary because we know if it ever happens, it will be many years in the future."
HIV vaccine research could continue with private funding, but it's important to have a dialogue and debate over its value in the context of public funding, Weinstein says. It would be a more efficient use of public funds to expand testing, treatment, and prevention programs, he says. The problem is that existing prevention strategies haven't been proven or attempted on a large scale, Lu says.
"I don't think it is healthy, productive, or useful to start a fight for funding among different subspecialties of HIV-related researchers or public health care workers," Lu adds.
Best public health strategy?
Although there are many strategies that are known to prevent HIV-1 transmission, there is a huge gap between knowledge and action, particularly in the area of human sexual behavior, Rowland-Jones says.
"After four years of living and working in Africa, I am not convinced that prevention strategies alone are likely to be effective on the scale necessary to combat the HIV-1 epidemic," she says.
The best public health strategy is to look hard at how best the available prevention measures, together with future vaccines, can be deployed in settings of poor health service infrastructure, demoralized health personnel, and competing health and economic priorities, she says. "All of these will be essential to slow the spread of HIV-1 in the developing world," Rowland-Jones says.
Conclusive studies indicate that people whose viral load is undetectable are virtually not infectious anywhere else, Weinstein says. "I cannot think of a more effective prevention strategy than not being infectious," he adds.
Because 90% of the people living with HIV/ AIDS today do not know they are HIV-positive, and a small portion of those who are infected receive antiretroviral therapy, the world health community is not taking advantage of the benefits of treatment for prevention, Weinstein says.
Rowland-Jones says, "All over the world, people are dying daily of diseases that we already know how to prevent. I don't think the failure of one candidate vaccine rules out the possibility of generating an effective vaccine in the future," she says. "The problem of generating an HIV-1 vaccine is enormous, but I do think it will ultimately be solved."
For example, vaccine researchers could study people who naturally control HIV-1 infection without the need for antiretroviral therapy, Rowland-Jones says. "In our studies in West Africa, we have focused on infection with the second HIV strain, HIV-2, where the majority of infected people live to a ripe old age without any signs of immunodeficiency," she explains. "Yet those who become sick behave exactly as if they had HIV-1."
This model of attenuated human infection with an HIV strain that clearly can kill people, but usually doesn't, has been neglected by the research community, Rowland-Jones adds. "It could provide valuable insights into protective immunity," she says.
References
1. Harari A, Bart P, Stohr W, et al. An HIV-1 clade C DNA prime NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses. J Exp Med 2008; 205:63-77.
2. Wang S, Kennedy JS, West K, et al. Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime-protein boost HIV-1 vaccine in healthy human volunteers. Vaccine 2008; 26:1,098-1,110.
AIDS Healthcare Foundation (AHF) of Los Angeles recently raised a stir when the organization's president and its medical chief announced that it was time for the federal government to stop funding research for the HIV vaccine and to put that money into prevention and treatment that works.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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