pre-exposure prophylaxis (PrEP) is adopted and is effective as an HIV
prevention method depends crucially on people’s subjective assessment of
whether they are at risk of HIV, and their cultural and moral beliefs about
whether they should take PrEP, the second IAPAC summit on controlling the HIV epidemic with
heard last week.
Amico of the University of Connecticut told the meeting that wide variability
in adherence in the randomised controlled trials of PrEP “may signal poor
acceptability, but could also signal community or cultural conflicts with the
research paradigm itself”.
drew attention to how PrEP and other prevention studies conducted in the last
ten years, especially in poorer countries, had attracted a “post-colonial
narrative”. In this, while trial participants might see themselves as trying to
ensure their health and aid others through trial participation, they were often
surrounded by a community suspicious that they were enrolling in the trial
purely for financial gain, and that trial investigators were harming
participants; myths sprang up about participants’ blood being sold or their
being deliberately infected with HIV.
studies have been surrounded with suspicion in richer countries too, but
participants’ adherence seems to be lower in poorer
settings, Amico added: this has been seen consistently, from the MTN
001 pill/gel comparison study,
where adherence in US women was 84% but in Ugandan women only 39%, to the open-label extension of
the iPrEx study
(where, even though participants knew they were taking active drug, adherence was
still only 60% in Peruvian sites, and did not match the 80 to 90% adherence seen
in US sites).
young, being single or in a non-exclusive relationship, heavy alcohol use, distrust
of the provider and low perceived risk from HIV or perceived benefit from PrEP
were all associated with low adherence. Using drug level monitoring, while it
might be useful to researchers in knowing who was using the product, would not
necessarily increase adherence or the reliability of self-reported adherence if
forces in trial participants’ lives continued to make adherence difficult, Amico
Young people, who may need PrEP most, especially struggle to adhere to
it: in a companion presentation (see more below), Ken Mayer of Fenway Health in
Boston showed that adherence in under-25-year-olds enrolled in iPrEx was only
44% compared with 73% in over-25s and a
study of gay young people in Chicago had difficulties in recruiting and adherence,
partly because of lack of settled accommodation.
said that products that were matched to common practices or that addressed
multiple needs might be better: injectable agents with less frequent dosing,
slow-release devices such as a vaginal ring, dual-purpose products such as
joint contraceptive and PrEP formulations, and intermittent PrEP might in
future match PrEP better to people’s needs.
was still too early to say what adherence to PrEP would be in the real world,
beyond the randomised controlled trials, Amico added. She stressed the vital
role of social scientists. Firstly, social science findings would help to
design trials to take account of drivers of product use, strategies to promote
product use, new tools such as PrEP as an option in a suite of prevention
alternatives, and monitoring feedback strategies. Secondly, social science was
integral to ongoing implementation research in demonstration studies and
rollout, to establish patterns of product use and establish how best to
intervene to support adherence.
Baeten, principal investigator in the Partners
PrEP study, said that interest in participating in trials is growing as
more people hear of PrEP. In San Francisco, a PrEP demonstration project started
enrolling 600 gay men and transgender women in July and there is currently a
waiting list of over 50 people. A demonstration project in Kenya and Uganda enrolled 90%
of the maximum number of people envisaged. Tools to identify those most
appropriate for PrEP may need to be developed to identify those most at risk, as
people are not always very good at estimating their own risk.
the other hand, people will not take PrEP unless they are motivated to do so
and feel at risk. For this reason,
Baeten said, he expected PrEP use to be very different in the real world;
people undoubtedly would use PrEP as and when they felt the need to, and needed
education on safe ways to do this.
is no evidence as yet that PrEP will inevitably compromise condom use, even in
open-label studies; but randomised controlled trials (RCTs) are not the real
world. In RCTs, condom use has tended to be high, whereas in some pilot
trials, especially in trials for gay men, the participants coming forward are tending to be very high-risk people who never or rarely
also needed to be given to PrEP discontinuation, Baeten added. Unlike HIV
treatment, PrEP need only be taken during periods of risk, but criteria and
support structures needed to be developed that would enable people to come off
needed to be integrated into HIV and STI testing and treatment, Baeten suggested,
as part of a whole package of sexual health services. The Partners PrEP demonstration
project, which only
enrols heterosexual couples, is now offering PrEP specifically for a six-month period while the
HIV-positive partner starts treatment, in order to allow them time to become
were undoubted risks to setting up PrEP programmes if they featured low adherence,
he added, but in many countries, even if HIV incidence stays steady, HIV
prevalence will inevitably rise. In the end, he said, the risk of adopting PrEP
too slowly may be higher than the risk of not adopting it at all.
number of PrEP pilot studies continues to expand. Ken Mayer gave details of
ongoing or planned studies from South Africa, Nigeria, India, Kenya and Uganda, while in the US nearly 3000 people are currently enrolled or about to be enrolled
in demonstration projects. He compared current levels of PrEP awareness and acceptance
with initial low awareness and slow uptake of prevention-of-mother-to-child-transmission programmes.
addition, there were other randomised trials addressing unanswered research
questions. The HPTN 067 (ADAPT) trial would examine three different PrEP
regimens (daily, twice-a-week or pre-sex Truvada); NEXTPrEP was looking at maraviroc (Celsentri)
in various combinations with or without tenofovir; in Europe, IPERGAY in France
was looking at the efficacy of a pre- and post-sex regimen; and PROUD in England
at the behavioural consequences of immediate PrEP versus the offer of it in a
the US, demonstration projects are looking at how to integrate counselling and
support into PrEP programmes. Initial qualitative data from a San Francisco
Health Department project suggested that the social advantages participants saw
in PrEP included decreased anxiety about transmission, increased communication
and disclosure to partners, increased intimacy and trust, an increased sense of
community and self-efficacy, and increased sexual pleasure.
On the other hand,
the social disadvantages included feeling stigmatised for taking PrEP, concerns
that it would influence them towards risky behaviour, an increase in negative
reactions from healthcare workers unacquainted with PrEP and, already, a concern
about how to access PrEP after the end of the demonstration project.
had to be part of a combination approach to prevention, said Mayer, that
included initiatives to increase testing; risk assessment; adherence
counselling; and interventions to help people with depression, substance use, and relationship dynamics
that might impact on people’s ability to control their HIV risk and sexual
health. HPTN 065 is a study to assess the feasibility of such a community-level 'test,
link to care, plus treat' strategy (TLC-Plus) in the United States that will
include PrEP as one of its components.
the demonstration projects, an initial study (reported
by aidsmap.com) had found (to date) 1447 individual patients being
prescribed PrEP by a variety of physicians, a majority of them family doctors
or nurses not involved in HIV care. Individual requests for PrEP were still
relatively uncommon outside the studies; Fenway Health had only seen 45 people
coming forward for it since the US Food and Drug Administration licensed it in
August 2012, though numbers were increasing, with nine prescriptions in the
last month with data (May 2013). Mayer
said that engaging and educating physicians about PrEP would be crucial to its
future as a prevention method – which would involve updating them about HIV.