US gay youth PrEP study meets recruitment and adherence problems

A small six-month pilot study of the feasibility and acceptability of pre-exposure prophylaxis (PrEP) in young gay men aged 18 to 22 in the US found that although participants reported adherence levels of 80%, their actual adherence (in the previous 48 hours, as measured by drug concentrations) fell from 65% to 20% during the study.

Young people's mobility appeared to be the largest reason for poor PrEP adherence, with 60% reporting 'being away from home' as a reason they did not take their pills.

This was a placebo-controlled study, so participants did not know if they were actually taking PrEP. Halfway through this study, the results of the iPrEx PrEP trial were announced; at that point the study was unblinded and all participants were given the option to take PrEP. Adherence after unblinding will be reported in another paper, and it will be interesting to see if there is a difference in adherence when participants know they are taking PrEP.

The study enrolled 68 young gay men (mean age 20) from Chicago. The intention had originally been to enrol 100, but although 753 potential participants were contacted and 241 met eligibility criteria (the most relevant of which was having had unprotected anal sex at least once in the last year), only 68 were enrolled and 58 randomised. Only 17% of those initially assessed (via a mobile-phone risk assessment tool) attended a screening appointment, though in many cases this was because researchers capped enrolment at about five participants per month due to limited staffing at the trial site. Low staffing, the researchers told Aidsmap, led to long wait times for eligible participants and thus loss to follow-up when staff tried to contact them later. Once youth were enrolled in the study, however, retention was high: 98.5% consistently attended appointments.

Only four out of the 58 randomised men were of white ethnicity (7%): 53% were African-American and 37% were mixed race or of other ethnicity such as Hispanic. Even though a majority of participants had attended some tertiary education, a third of participants had spent at least one night in emergency accommodation, 17% had exchanged sex for money or a place to stay, and 15% had been 'kicked out' (the researchers' phrase) of their family homes due to their sexual orientation.

Of the 743 initially contacted, 3% (22 individuals) were excluded because when screened they turned out to have HIV – a considerably higher undiagnosed positivity rate, say the researchers, than among gay youth in the US generally.

Participants were randomised into three groups of 20, 19 and 19 individuals each. All participants received a group-based behavioural intervention called Many Men, Many Voices as a weekend seminar in small groups (average eight participants). This workshop, which is one of those recommended as of proven effectiveness in the US Centers for Disease Controls' DEBI (Distribution of Effective Behavioral Interventions) site, helps gay men discuss sexual risk and self-protection in the context of being in both a racial and a sexual minority.

One third of participants received no further interventions apart from monthly clinic visits, during which they could receive safer-sex counselling as well as health monitoring. One-third were randomised to also take a once-daily Truvada (tenofovir/emtricitabine) pill as PrEP, while the remaining third took a daily placebo pill.

Adherence was assessed by self-report, using both a straightforward questionnaire and a calendar prompt to jog participants' memories, by pharmacy refills, and by drug levels in plasma.

By self-report, participants reported taking 72% of doses in the first two months of the study and this increased to over 80% in the following four months. Drug-level monitoring told a very different story; while adherence was moderately good initially at about two-thirds of doses taken and was in the 50 to 60% range in the first three months, it then declined steadily and was only 20% by month six. (It is important to emphasise that the drug-level assay used could only measure drug taken in the last 48 hours, so drug level monitoring could have missed intermittent use, e.g. at weekends.) The biggest single reason for failing to take the daily pill was that participants were away from home (60% cited this as the reason, or one of the reasons).

There was a warning of low adherence in that twice as many participants who expressed an opinion said they did not like the idea of having to take a pill every day compared to those who said they liked it, and a majority were also not keen on the size or taste of the pill. In contrast, the large majority of participants liked taking part in the study as a whole, appreciated the regular health and behavioural monitoring at study visit, and valued having safer-sex counselling.

There was a trend to less unprotected sex over the study period, but this was not statistically significant and may be just as unreliable, say the researchers, as self-reported adherence. There were 17 diagnoses of STIs during the study, with HPV (genital warts) being the most common.

Being randomised to a daily pill did change some opinions, with a majority of members of both PrEP and placebo groups saying they were less worried about HIV infection now they were in the study, compared to hardly any non-pill takers. The same applied to anxiety about having unprotected sex. There was no statistically significant relationhip between taking a pill and having unprotected sex.

The study shows that it is possible to enrol young gay men into a PrEP study, but also shows they may need considerably more support to use it effectively as an HIV prevention measure. Researchers were unable to recruit more people into the study largely because participants' contact details kept changing and staff could not locate them.  In other words, the same factors affect young people's adherence to PrEP as their adherence to HIV treatment, and young peopel of both sexes and different cultures find adherence difficult, as seen in the results of the African VOICE study.

After this pilot trial was finished, however, participants were invited to joing the iPrEx OLE open-label extension of the iPrEx PrEP study. Forty-six of them did and have completed 72 weeks on that study.  Youth-specific figures from iPrEx OLE are awaited.