Leading AIDS experts criticise major US vaccine trial

16 January 2004

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US scientists and AIDS advocates yesterday called into question the US National Institutes of Health decision to proceed with trials of a controversial vaccine strategy in Thailand, saying the $120 million needed to run the trial would be better spent on newer vaccine candidates with a better chance of success.

Writing in the journal Science, 22 leading basic scientists and vaccine researchers called on the US National Institutes of Health to review whether it is wise to proceed with the study. “We seriously question whether it is sensible now to conduct a third trial that, in our opinion, is no more likely to generate a meaningful level of protection against infection or disease,” the scientists write.

The study will use a combination of ALVAC, a canary pox-based vaccine designed to stimulate CD8+ T-cell responses to HIV, and a booster using AIDSVAX (a gp120-based vaccine designed to stimulate antibody responses). However the scientists say that both vaccines have proved weak or ineffective in studies so far. In particular AIDSVAX has failed to demonstrate any clear protective effect in two large phase III studies reported in 2003, and the authors of the letter throw particular doubt on the claim that a combination of the two vaccines might somehow stimulate HIV-specific CD4 T-cell responses.

Glossary

phase III

The third and most definitive stage in the clinical evaluation of a new drug or intervention, typically a randomised control trial with the new intervention compared to an existing therapy or a placebo, in large numbers of participants (typically hundreds or thousands). Trial results are used to evaluate the overall risks and benefits of the drug and provide the information needed for regulatory approval.

efficacy

How well something works (in a research study). See also ‘effectiveness’.

CD8

A molecule on the surface of some white blood cells. Some of these cells can kill other cells that are infected with foreign organisms.

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

gp120

A glycoprotein on the HIV envelope. gp120 binds to a CD4 receptor on a host cell, such as a CD4 T lymphocyte (CD4 cell). This starts the process by which HIV fuses its viral membrane with the host cell membrane and enters the host cell.

The scientists fear that the study will fail, and warn that the cause of AIDS vaccine development cannot afford another large and costly failure.

“The scientific community must do a better job of brining truly promising vaccine candidates to this stage of development,” said Professor Michael Lederman of the AIDS Clinical Trials Unit at Cleveland University Hospitals,”otherwise we risk eroding public confidence in the research.

One of the leading AIDS advocacy groups in the United States supports yesterday’s letter to Science.

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"Even if the current trial proceeded to conclusion and did show some degree of vaccine efficacy, the design of the study would make it impossible to know whether ALVAC alone was responsible, or if the addition of AIDSVAX had improved – or worsened – the outcome" said Richard Jefferys of Treatment Action Group yesterday. "A second, even larger phase III efficacy trial would then have to be performed in order to answer this question - a mind-boggling example of short-sighted planning for which the NIH should be called to task."