More oil on the fire for Thai HIV vaccine trial

Disagreements between HIV/AIDS vaccine developers regarding a vaccine efficacy trial currently underway in Thailand were given a fresh airing this week, in an exchange of letters published in Science.

Fifteen researchers from institutes around the world wrote a letter in response to previous criticism of the Thai trial that was published in January 2004 (see World’s biggest HIV vaccine trial ‘is a costly mistake’). They argue in the trial’s favour, saying that it will test the efficacy of an important vaccine strategy.

In response, the authors of the original critique maintained their stance, saying that the trial will almost certainly fail and this will come at a high financial and social cost. They say the design of clinical trials needs to be more stringent and transparent. “A scientifically informed, internationally coordinated, and forward-thinking process to guide HIV vaccine research and development now needs to be created — urgently,” they write.

The Thai phase III clinical trial is meant to test the efficacy of a ‘prime-boost’ vaccine strategy, which combines two vaccines in the hopes of eliciting a stronger and more varied immune response.

The controversy arises from the use of an HIV protein called gp120 to elicit an immune response against the virus. Some researchers, including the authors of two of this week’s Science letters, say previous evidence clearly demonstrates that gp120 will not be able to elicit an adequate immune response. On these grounds, they say, the Thai vaccine trial is wasting valuable resources.

In today’s letter “Support for the RV144 HIV vaccine trial”, Robert Belshe and colleagues retort that, even if the vaccine being tested in Thailand is not effective, the trial will still yield important results for future vaccine development.

“To cut off a line of scientific inquiry prematurely undermines basic tenets of drug and vaccine development, especially in the developing world, and could deny the benefit of potentially important new knowledge,” they say.

To this, the critics respond, “we continue to believe that greater selectivity is needed to ensure that the products that reach phase III efficacy testing are promising ones.”

The authors say that repeated failures of phase III trials could have a number of serious adverse consequences. “These include erosion of the will of populations to participate in such trials and the willingness of governments, organisations, and corporations to fund not just the trials themselves, but also, and most critically, research directed to developing a successful AIDS vaccine.”

Robert Gallo, director of the Institute of Human Virology and the University of Maryland, United States, was one of the signatories of the critique published in January. He chose not to sign their latest letter in this week’s issue of Science “because I do not want to engage in a new debate over process”.

In his own separate letter, he maintained that “given the available evidence, there is little reason for optimism that the [Thai trial] vaccine will protect a human being from HIV infection”. He says the decision to carry this potential vaccine through to a phase III trial was based on previous results that were “no better” than “woefully inadequate”.

However, he says it may be too late to interrupt the current trial, but believes it should be pursued “with full understanding and admission of its scientific weaknesses”.

“Not to do so encourages the continued use of extremely expensive and undefined efforts that are justified solely by the tenuous notions that ‘we may learn something’ or that we need to have candidates ‘in the pipeline’.”

A fourth letter, written by the board, staff and executive director of the AIDS Vaccine Advocacy Coalition, agrees that cancelling the trial, which has already enrolled more than 3000 volunteers, would send a negative message to vaccine developers.

Reference: Science 305, 177 (2004)

Link to full text of letters in Science