Who will PrEP be for?

Whether 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 antiretrovirals heard last week.

Rivet 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”.

She 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.

PrEP 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).

Being 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 added.

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.

Amico 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.

It 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.

Jared 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.

On 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.

There 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 use condoms.

Thought 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 it appropriately.

PrEP 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 virally undetectable.

There 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.

The 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.

In 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 year’s time.

In 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.

PrEP 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.

Outside 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.