Adherence

One interesting finding was that adherence in the study was not only lower than expected, it was also a lot lower in reality than it was on the basis of participants’ own reports, or by counting the number of pills dispensed. On the basis of what iPrEx was able to determine, we cannot really say that PrEP will work 19 times out of 20 if you have perfect adherence, nor can we say (as one agency concluded) that PrEP definitely won’t work if your adherence is less than 90%.

“All we can say,” Susan Buchbinder, one of the iPrEx investigators told Aidsmap, “is that it does look like people who were able to take their drug more regularly were more likely to be protected."

On the one hand, this is discouraging as it suggests adherence will be a big challenge in making PrEP work; on the other hand, it suggests that the potential efficacy of PrEP is very high – as efficacious as condoms, if not more so – and if we can help patients achieve high adherence it could offer significant protection against infection.

Bob Grant, the study’s global Principal Investigator, said: “Although daily use of a pill to prevent something is challenging, it is feasible. We know from the use of statins to prevent high cholesterol and, perhaps more relevantly, oral contraceptives to prevent pregnancy, that people will adhere to preventative regimens if they see enough benefit in them.”

Grant said that the iPrEx researchers would be looking into the adherence and efficacy question much more deeply, and would be checking thousands of other stored samples for drug levels to get a much more accurate idea of the true adherence levels in the trial. These investigations would not only help establish a truer picture of efficacy, but also look at whether people gave up taking their pills at characteristic times. If those who stopped taking Truvada did so very soon after starting, for instance, it might suggest that the reason was side-effects.

Grant emphasised that one of the most promising aspects of the trial was that efficacy was highest in the highest-risk people: the men who had significant levels of unprotected anal sex as the passive partner. In fact, there was little measurable efficacy in men who denied being receptive in anal sex.

“It became apparent early in the trial,” he said, “that iPrEx was attracting the highest risk individuals. Many had never had an HIV test before or come forward for help with prevention, yet here they were volunteering to be part of a prevention initiative. It was also just as effective in the youngest men in the study as in anyone else.”

A rollover study offering every participant in the study open-label Truvada started in early 2011. This study, which will last till 2013, will allow the investigators to monitor for longer-term side-effects and long-term changes in behaviour.

Importantly, the study will also use a completely different style of adherence counselling, which was piloted in the last few months of iPrEx. Feedback from interviews with participants showed that they found being reminded about adherence by the same people who were giving them blood tests was not conducive to being honest about adherence problems. The rollover study will, therefore, feature adherence counsellors who are completely separate from the staff doing monitoring tests, and who will not be informed of patients’ adherence levels as assessed by blood tests. All patients will be treated equally and asked about what factors are making it easy or hard to take the pills.