VaxGen trials likely to go to full term

Dr Donald Francis, Chief Executive of VaxGen, said at the AIDS Vaccine 2001 conference in Philadelphia on Friday afternoon that he expected the clinical trial of his company’s AIDSVAX B/B product, which has enrolled 5,418 volunteers in the USA, Canada, Puerto Rico and Amsterdam, to continue to its planned conclusion at the end of 2002.

The independent Data and Safety Monitoring Board for the trial will take a first look at the efficacy data this November. It could then stop the trial if it is already clear that the vaccine reduces HIV transmission by at least 30 per cent. Safety data are reviewed throughout the process and have been reassuring with no unexpected hazards reported. Dr Francis stressed that for the trial to be stopped prematurely the vaccine would need to be highly effective. Continuation of the trial at this stage would therefore not imply that the vaccine has failed. He said that enough people had acquired HIV during the trial to be confident of a result, one way or the other, at the end of the process.

Risk Behaviour Patterns

Dr Brad Bartholow of the US Centers for Disease Control and Prevention described HIV-related risk-taking reported by volunteers in the VaxGen trials. Criteria for enrolment had included, for gay men, unprotected anal sex at least once in the previous 12 months other than with a regular HIV negative partner. For women, a partner diagnosed with HIV, multiple male sex partners or a history of using crack cocaine (which in many US cities is linked to HIV risk through sexual transmission) were required. Injecting drug users were, however, excluded.

Volunteers were asked what they thought about the efficacy of the vaccine and whether they thought they had been given the vaccine, or a placebo, or didn’t know (most said they didn’t know).

There was a general trend, among gay men and among women, to have less unprotected anal or vaginal sex as time went on through the trial. This also applied to higher-risk behaviour, i.e. unprotected sex with someone who might be or is known to be HIV positive, and receptive unprotected anal sex with a known positive partner.

Gay men who thought, 12 months into the trial, that they had received the vaccine, were slightly more likely to report unprotected sex than gay men who thought they had received the placebo or who “didn’t know”. This was especially true of those who thought the vaccine worked. At the same time, this group showed the same rate of reduction in risk-behaviour as other gay men. The fact that the behaviour difference existed from the start of the trial, before any injections were received, argues against the belief “causing” the risk-taking. A more likely explanation is that at least some gay men who know they have taken risks are talking up the vaccine to themselves as reassurance.

Trends in behaviour among the women enrolled in the trial were more difficult to analyse. Women volunteers are in a small minority – 308 – and their educational background is different, with few having more than high school education, in contrast to the better-educated gay male volunteers. Focus-group research suggested that some of the women weren’t sure whether the “vaccine” or the “placebo” was the active preparation, despite much effort through the trial to explain the difference.

A slide session (McLellan) and a poster (Novak) explored the experience and views of women volunteers taking part in the trial suggested a need for support groups in which volunteers are able to share experience with others from the same community.

VaxGen in Thailand

Dr Punnee Pitisuttithum from Mahidol University, one of the partners in the Bangkok Vaccine Evaluation Group described the trial of VaxGen’s AIDSVAX B/E product in Thailand. This trial enrolled 2,545 injecting drug users by August 2000. So far, 98 per cent of trial volunteers have continued to attend clinics for follow-up sessions, although the fact that 96 per cent of eligible volunteers have received four injections may give a better guide to drop-out rates – which are still remarkably low. 93 per cent of participants in this trial are male, with an average age of 26. The first interim assessment of efficacy is due late in 2002 and final results are expected late in 2003.

Speaking at a press briefing, Dr Pitisuttithum was asked about incentives for trial involvement, about treatment offered to those who seroconverted, and how these impressive follow-up rates had been achieved. She paid tribute to the commitment of the volunteers themselves and more than 200 clinical staff who were supporting those volunteers. Volunteers’ out of pocket expenses for attendance are met, but this hadn’t been given as a reason for participation when volunteers were asked why they were taking part. She doubted that it would be an undue incentive, given the amount of commitment demanded from volunteers, including answering detailed and intrusive questionnaires about risk behaviour on each visit. Indeed, as part of the informed consent process, volunteers had been required to pass a comprehension test to make sure they understood what they had agreed to.

The standard of treatment offered in the VaxGen trial to volunteers who seroconverted was set within Thailand and had actually changed already during the course of the trial, with triple combination therapy as the standard of care where antiretrovirals were indicated. Dr Francis observed that while VaxGen had made a donation in Thailand towards the cost of clinical care in the communities where the trial was taking place, it was not directly funding the treatment of people diagnosed HIV positive in the trial. This was and would remain the responsibility of the Thai partners in the consortium running the trial.

Learning From VaxGen’s Trials

Whether or not VaxGen’s products prove effective, it is already clear that much will be learned that will help in the planning of future trials.

Dr Timothy Mastro, who now heads CDC’s vaccine-related research programmes, told Aidsmap that in the VaxGen trials, volunteers who did seroconvert were tending to wait for at least a couple of viral load tests before making decisions about treatment. This made sense to most people, based on the possibility that vaccination – if they had indeed received the vaccine – might limit their viral load without treatment. This was very encouraging in relation to the prospects for evaluating future vaccines that might not prevent infection but were much more likely than AIDSVAX to limit viral load.