Bob Grant of the iPrEx study team provided the first data on
iPrEx-OLE, where OLE stands for Open-Label Extension. In this study,
participants in the
original iPrEx placebo-controlled study, which reported an
overall efficacy of 44% for tenofovir/FTC-based PrEP, were invited to
join an extension study in which they all received tenofovir/FTC. The hope was that, if subjects knew they were not taking a
placebo, adherence and therefore efficacy might be higher.
efficacy results for iPrEx-OLE will be published in 2014, but Grant
announced data at IAS 2013 on factors associated with participants wanting to
join iPrEx-OLE and staying in it, and also on drug levels in all
participants – seen as the gold-standard way of ascertaining
terms of recruitment, 2340 people were eligible to join iPrEx-OLE,
and 1526 of these (65%) said they wished to enrol in the open-label
study, but only 1038 (44%) actually started taking PrEP.
Of those who did not continue, 15% dropped out as the placebo-controlled
trial was still ongoing, 8% in the time gap between studies, and 12% just
before iPrEx-OLE started, at the time the results of the
placebo-controlled study were unblinded and individuals learned what
they had taken. Another 5% became HIV positive in the gap between
far the most common reason for not
continuing was concern about side effects: 49% of non-continuers
cited this as a concern.
Other concerns were less common:14% said
they could manage their HIV risk without PrEP, 15% said they didn't
like taking a pill daily, and 12% said they didn't like taking the
pills at all. Seven per cent feared people would think they had HIV
if they took PrEP and 3% feared it would 'out' them as gay. Nine per
cent feared developing drug resistance. These are non-exclusive
figures: people could cite more than one reason.
who elected to continue into iPrEx-OLE were older (76% of over-30s
continued versus 68% of under-25s) and were less well educated.
Wishing to continue was related to HIV risk: 79 and 74% of those who had
anal sex with, and without, a condom versus 64% who said they did not
have anal sex continued into iPrEx-OLE.
surprisingly, 62% of the roughly 50% of placebo-controlled study
participants who had undetectable drug levels wanted to continue: 75%
of those who always had detectable drug levels did.
Drug-level monitoring was done in all participants, using a test sensitive
to one dose of drug in the previous three days. To avoid the 'white
coat effect', where non-adherent subjects take a pill immediately
before their clinic visit, a drug level test was performed on either
week 4, week 8, or week 12 of the study, but participants were not
drug was found in 61 to 71% of subjects. Except for one US site, drug detection was more common in all participants in
iPrEx-OLE than in the original trial. However, rates of drugs detection were
only slightly higher in the other
US sites and the Brazilian, Thai and South African sites. In the sites
in Peru and Ecuador, however, where only 30% with detectable drug was found at
some sites in the original trial, over 61% had detectable drug at all sites, indicating a
doubling of adherence.
drug was associated with older age and higher education: there was a
slight tendency for participants who had condomless sex to have less
detectable drug, but this was not statistically significant.
if he was disappointed that about 65% of 44% of participants in the
original study (28%) both elected to continue into iPrEX-OLE and take
the study drug, Bob Grant pointed out that taking PrEP daily was not
a requirement of staying in iPrEx-OLE: participants could stop and
restart PrEP in consultation with researchers and if they agreed to an
HIV test before resumption.
added: “PrEP is not for everyone, or even necessarily for a
majority. We feel however that PrEP is an indication for a lot of
people who for one reason or another cannot access or use condoms.
are also finding consistently that HIV prevention methods are
synergistic and do not detract from each other: starting PrEP may
well also involve testing more often, being linked to care if you do
test positive, and accessing a range of support.”