Is it really time to give up on the hope of finding a preventative HIV vaccine?
Is it really time to give up on the hope of finding a preventative HIV vaccine?
Experts offer a mixed view of the vaccine's future
AIDS Healthcare Foundation (AHF) of Los Angeles, CA, 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 have already opined that 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 United States 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 non-infectious."
In light of the incredible advances in HIV treatment, it makes more sense to spend the millions funneled into HIV vaccine research into expanding HIV testing, treatment, and prevention, Weinstein says.
"HIV and AIDS have evolved over the last 20 years, and we have faced many challenges and obstacles," says Homayoon Khanlou, MD, chief of medicine for AHF.
"If we were able to obtain a vaccine, we should have had it by now," Khanlou states. "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.
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 either 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.
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 refers specifically to the 2008 phase I vaccine study published in the Journal of Experimental Medicine by A. Harari, 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 percent 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 these are very early results and may 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," Lu says. "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 impacting 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," Weinstein says. "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 sub-specialties of HIV-related researchers or public healthcare workers," Lu adds.
"Although there are many strategies that are known to prevent HIV-1 transmission, I think 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."
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 adds.
"There now are conclusive studies 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."
Since 90 percent 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.
"All over the world, people are dying daily of diseases that we already know how to prevent," Rowland-Jones says.
"I don't think the failure of one candidate vaccine rules out the possibility of generating an effective vaccine in the future," Rowland-Jones says. "The problem of generating an HIV-1 vaccine is enormous, but I do think it will ultimately be solved."
For instance, vaccine researchers could study people who naturally control HIV-1 infection without the need for antiretroviral therapy, she notes.
"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," Rowland-Jones 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, she adds.
"It could provide valuable insights into protective immunity," Rowland-Jones says.
One of the problems with the current HIV vaccine development is that there is a concentration of similar ideas or a not-well-defined selection process of candidate vaccines, Lu says.
"These problems should be addressed, and the system should be improved, including any new mechanisms that can have a more transparent and flexible funding process to identify and quickly advance any promising concepts for human testing," Lu says. "A complete stop of HIV vaccine research is going to destroy the entire system, and then it will be true that there will be no chance to have an HIV vaccine in the future."
References:
- Harari A, 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.
- Wang S, 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;26:1098-1110.
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