The other 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. Participants
claimed at least 90% adherence but a substudy, in which drug levels in
participants’ blood and immune cells were measured, suggested that in reality
it was about 50%.
Subanalyses were done
suggesting that, based on pill counts and self-reports, the efficacy of PrEP in
people who took more than half their doses was 50% and in people who took 90%
of their doses was 74%. However the significantly lower ‘real’ adherence levels make analyses based on pill counts unreliable, as they assumed all pills dispensed
We can’t really say, therefore, that PrEP will definitely work 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."
This on the one hand 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.”
He 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
He 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
will start 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
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.