Examining future lessons of HIV vaccine trials

A recent issue of Vaccine included a paper that asked this question: "What can HIV vaccine trials teach us about future HIV vaccine dissemination?" (Newman, et al. Vaccine 26 (2008), 2528-2536 -- free abstract).

Based on focus groups conducted in the Los Angeles area, the researchers map the common barriers between participants' willingness to participate in vaccine trials and the acceptability of a hypothetical vaccine. In both cases, common themes emerged, including fear of vaccine-induced infection, false positives to HIV tests and associated consequences, side effects, partial vaccine efficacy, AIDS stigma, and mistrust of government, among others.

The authors conclude that these parallels provide a valuable opportunity to use HIV vaccine clinical trials to study issues related to acceptability of an approved vaccine. They write:

"...Rigorous sociobehavioral research conducted in conjunction with HIV vaccine trials, in addition to facilitating informed enrollment in safe and ethically conducted trials, may provide an empirical basis for targeted sociobehavioral interventions to ensure the effectiveness of future HIV vaccines in controlling the epidemic."

Updates: HIV vaccine reassessment; 2nd rotavirus vaccine approved; Avian flu vaccine supply

Here are a few updates on topics we've been covering over the past several months:

• HIV vaccine research -- Several months after the failure of what was billed as the 'most promising' HIV vaccine candidate, NIAID organized a meeting late last month to reassess the state of HIV vaccine research and plans for the future. The "Summit on HIV Vaccine Research and Development" garnered significant media attention from the Washington Post and New York Times, among other outlets. The apparent take-away message from the meeting was that renewed effort must be directed toward basic research and novel ideas. A subsequent Times editorial argued that the potential benefit of a vaccine is too great to give up hope. A webcast of the meeting is available at the NIAID summit website.

• Rotavirus vaccines -- As expected, on Thursday, FDA approved GSK's Rotarix, now the second rotavirus vaccine available in the United States. Here's a story from the Associated Press, the FDA press release and the GSK release. The major difference between Rotarix and Merck's RotaTeq is that Rotarix requires two doses compared to three for RotaTeq. No word yet on the price of Rotarix, which had already been licensed in over 100 countries. It is expected to be available in the U.S. later this year.
  

• Pandemic flu planning -- Another update on the federal government's pandemic flu planning was released by HHS Secretary Michael Leavitt late last month. Updates on vaccine development and stockpiling figure prominently in the report. It notes that enough pre-pandemic vaccine for 13 million people was stockpiled by the end of 2007. This CIDRAP News story has more details.

"Most promising" HIV vaccine trial stopped; vaccine not effective

In what a colleague at Penn--an HIV researcher--describes as "very big and very disappointing news", Merck announced Friday that it was halting clinical trials on what was viewed as a highly promising HIV vaccine candidate, the most advanced vaccine that employed a new strategy attempting to stimulate T-cell immunity against the virus. An interim analysis of research data found that the vaccine was not effective.

Here's the front page story from Saturday's New York Times -- Failure of Vaccine Test is Setback in AIDS Fight, and more coverage from Scientific American, The Associated Press, and The Washington Post. Here are official statements from Merck, NIH, and IAVI.

Also of note is this editorial in today's Philadelphia Inquirer, "Starting fresh for an HIV vaccine."

HIV, Malaria, TB: vaccine research issues and planning

Several items of note over the past few weeks on research for vaccines that would have the greatest potential benefit in the developing world:

-- HIV/AIDS: In the July-August issue of Health Affairs, a paper appears titled, "The Impact of An AIDS Vaccine In Developing Countries: A New Model and Initial Results." (free abstract). Among its findings, the paper notes that a vaccine with 50% effective administered to 30% of the developing world population (both reasonable estimates) could prevent 17 million infections in 15 years.

Speaking of HIV vaccines, the death of Dr. Edward Brandt was announced this weekend. Brandt was assistant secretary of HHS in the early 1980s when AIDS and HIV were first identified. His (and HHS secretary Margaret Heckler's) overly optimistic predictions of an HIV vaccine's arrival are featured prominently in Brandt's New York Times obituary. He opined that an HIV vaccine would be available by 1987, three years after HIV was identified.

-- Malaria: A news story in the current issue of JAMA reports on malaria vaccine development ("'Roadmap' AIDS Malaria Vaccine Efforts" -- free extract.) The story provides a very good summary of progress toward a malaria vaccine and challenges needing to be addressed. The 'roadmap' referred to is the Malaria Vaccine Technology Roadmap, the product of an international series of consultations.

-- Tuberculosis: We don't talk all that often about the development of new vaccines against tuberculosis, but a paper in PLoS Medicine ("Development of New Tuberculosis Vaccines: A Global Perspective on Regulatory Issues") summarizes the content of an international meeting on the topic. The paper summarizes many of the challenges facing vaccine development and offers recommend strategies to address them.

Update on HIV Vaccine Research Strategies

Despite the many challenges facing the development of a safe and effective HIV vaccine (many of which we've discussed previously), we continue to be interested observers in the status of HIV vaccine research, cognizant of the incredible benefits a vaccine would bring.

The latest New England Journal of Medicine includes a review article by NIAID Director Dr. Anthony Fauci and researcher Dr. Margaret Johnston titled "An HIV Vaccine -- Evolving Concepts."

It's a science-laden paper, but its conclusion reflects the increasingly modest hopes for a potential first-generation HIV vaccine. Johnston and Fauci describe a different type of vaccine, one that would alter the common understanding of the protection vaccines provide and create additional implementation concerns along with the potential for tremendous benefits...

" A vaccine that conforms to the classic paradigm of viral vaccines remains the goal of efforts to develop an HIV vaccine. Such a vaccine would induce immune responses that prevented the establishment of HIV infection by clearing virus before latent viral reservoirs were produced. This goal may not be realized with first-generation vaccines. The development of an HIV vaccine may diverge from the classic paradigm for viral vaccines. There is optimism that even a less-than-perfect vaccine could benefit both individual recipients and the at-risk community. By blunting the initial burst of viremia and reducing virus levels, such a vaccine could prolong the disease-free period and also reduce transmission. If licensed, such a vaccine will have to be delivered as part of a comprehensive, multifaceted, prevention program."

Gates gives $287 million for HIV vaccine research

News about the Gates Foundation making an enormous contribution to global health has become nearly a weekly occurrence lately. Today's headline is the announcement of 16 grants totaling $287 million to continue work toward a possible HIV vaccine. Here's the New York Times story, the AP story, and the press release from Gates with an accompanying background document offering details on the recipients and their projects.

The amount of funding is impressive in isolation but is even more staggering when compared to the total dollars directed to HIV vaccine work in years past. In 2004, for example, U.S. research totaled $582 million, with an additional $120 million worldwide. Yesterday's announcement marks a significant investment in the work and another strong show of support for it from Gates.

The Gates Foundation has been an active supporter of HIV vaccine research for several years, playing central roles in the creation and launch of the Global HIV Vaccine Enterprise (which we previously wrote about here). In fact, it's often difficult to determine where the Gates Foundation ends and the Enterprise begins, and vice versa. The grants announced yesterday fund projects linked to the Scientific Strategic Plan of the Global Vaccine Enterprise, awarded to very prominent vaccine researchers including Barton Haynes of Duke and David Ho of Rockefeller University, among others.

Newark Star-Ledger chronicles HIV vaccine efforts

It's been several months since we pointed to a story updating the quest for an HIV vaccine. This lengthy feature in today's Newark Star-Ledger is worth reading. Titled "AIDS at 25: For scientists in search of a vaccine, the elusive and ever-deadly HIV virus is a mystery that may never be solved," the story opens with a similar pessimism:

"After 25 years and countless billions of research dollars, some of the nation's top scientists say a vaccine that provides absolute immunity against the virus that causes AIDS -- the best hope of curbing the worst epidemic of our time -- may never happen.

Despite breakthroughs in treatments for people already infected with HIV, researchers have hit one obstacle after another in efforts to develop a vaccine, long considered the holy grail of AIDS research. The science, they say, is just too hard."

The story includes extensive quotes from several prominent HIV vaccine researchers, particularly Ron Desrosiers (Harvard and elsewhere) and Emilio Emini (currently at Wyeth, previously at IAVI and Merck). There's a surprising level of scientific detail for a newspaper piece, outlining many of the obstacles impeding the development of a safe and effective vaccine.

Washington Post looks at NIH-funded HIV vaccine trial in Thailand

The front page of today's Washington Post includes a lengthy story on the controversy surrounding the lone phase III HIV vaccine trial currently underway and details its links to the failed VaxGen trial of a few years ago. No news here, but a good feature recounting the failures of every large-scale trial of HIV vaccine candidate to date. An excerpt:

"For the past three years, such [research subject enrollment] gatherings have been held all over Thailand, exhorting young adults to take part in the largest, most expensive, most resource-intensive AIDS vaccine trial ever. Funded by the National Institutes of Health, it ultimately will involve 16,000 people and last 3 1/2 years.

But as the trial moves forward, at a cost of more than $120 million, some researchers are raising questions about its validity. They disparage its science, question its ethics and doubt its efficacy."

Unlike most large clinical trials in which there is significant confidence that the product being tested will likely be approved for public use, there's almost no one who would claim with a straight face that the vaccine in this trial has any chance of being the vaccine. Even in today's Post story, unnamed NIH scientists attempt to lower expectations, saying that the trial "may reveal new things about HIV" even if the vaccine itself fails.

This may be true, but it's a radically different goal to set for a 16,000-subject clinical trial. The ethical questions of asking for so many research volunteers for this type of exploratory work are many, as are the criticisms from the scientific community that the limited public research dollars for HIV vaccine research could be far better spent.

Papers of note in Vaccine

Among the many interesting papers published in the journal Vaccine, two that appeared in the May 8 print edition are worth mentions here (free abstracts, subscription required for full text):

• "Parental decision-making in childhood vaccination" -- In light of the reduced uptake of MMR vaccine in the U.K. on account of parental concerns about vaccine safety, the paper explores some of the psychological factors that impact decision-making, how 'risk' is understood, the role of the media in affecting public perceptions, and other aspects of decision theory relevant to vaccination.

• "A review of vaccine research and development: The human immunodeficiency virus (HIV) -- An up-to-date, extensively-referenced review article on the current state of HIV vaccine research, future directions, and scientific challenges that need to be overcome. Heavy on science, but an invaluable starting point for anyone seeking to learn more about the field.
  

Checking in on the Global HIV Vaccine Enterprise

As we've written previously, we're interested in the quest for a vaccine against HIV, what some consider to be the Holy Grail of infectious disease research. One of the most innovative aspects of HIV vaccine research is the creation of the Global HIV Vaccine Enterprise, a multinational consortium first proposed by leading researchers in 2003 and shortly thereafter supported by the G8 nations and the Gates Foundation.

Supporters of the Enterprise argue that it will foster collaboration, reduce dead-end experiments, and lead to more rapid progress in overcoming the significant scientific obstacles to a vaccine. Others wonder if consolidating much of HIV vaccine research under a large umbrella will stifle the creative ideas that sometimes, despite long odds, lead to breakthroughs. It's far too early to tell who's right, but if successful, the Enterprise model may have applications throughout vaccine research.

On Friday, the Chicago Tribune published a story about the initiative. No 'news' in the story, but a nice overview of the Enterprise and its rationale.

There was news regarding the Global HIV Vaccine Enterprise last week, though the announcement likely occurred too late for the Tribune story. Adel Mahmoud, the former president of Merck Vaccines, was named chief executive of the alliance, effective September 1. Here's the press release.

No news on the HIV vaccine front, but a story anyway...

This CNNMoney.com story today on HIV vaccine research has little news value. Its thesis seems to be that an HIV vaccine would be wonderful news for the pharmaceutical industry (nevermind mankind). Backed by a handful of quotes from industry analysts, the author states that a vaccine...

"could bring in blockbuster sales for the companies behind it, save lives, and possibly even improve Big Pharma's battered image, all at the same time."

Even for a business website, it seems as though the issue of 'saving lives' is getting short shrift. Overall, despite several analyst quotes noting that a safe and effective HIV vaccine is years away (if ever), its descriptions of phase II and III clinical trials still sends the impression that we're closer to a vaccine than anyone working in the field believes.

This post isn't intended solely to criticize the story and its author (although his reference to Tamiflu as an "influenza vaccine" slightly hurts his credibility). Rather, it is a good example of the difficulties of accurate, sound coverage of vaccines in the media, particularly when reporters -- especially non-science reporters -- must rely on a few quotes from 'experts' to guide their story. A piece such as this is harmless, but when controversies surface regarding vaccines, such coverage can be problematic. We'll be paying special attention to this phenomenon in the weeks and months ahead.

Finally, a note that the quest for an HIV vaccine and the ethics thereof are special interests of the Ethics of Vaccine project. While other vaccine-related issues are more immediate concerns to society (avian flu, supply shortages, HPV, safety, etc.), the potential benefits of an HIV vaccine are immeasurable. We're interested in the work underway worldwide to make that potential a reality.