One of the first studies of open-label pre-exposure prophylaxis (PrEP) for at-risk gay men in three US cities shows that although the proportion of those initially offered or seeking PrEP who ended up taking it was similar in all cities, the amount of interest in it differed substantially. It also found substantial differences in adherence between the cities, possibly due to a younger population in one, but lower adherence was not associated with lower motivation to take PrEP.
The demonstration project and its volunteers
From September 2012 to September 2013, 1059 HIV-negative gay/bisexual men and transgender women who attended sexual health clinics in San Francisco, Miami and Washington DC were offered an opportunity to be screened for eligibility for open-label tenofovir/FTC (Truvada) PrEP as part of a demonstration study run by the National Institute of Allergy and Infectious Diseases (NIAID).
A large minority (37%) approached the clinic proactively asking for PrEP, and they were 50% more likely to eventually be prescribed it, with 56% of those starting PrEP being self-referrals. In contrast, two-thirds of those offered PrEP by their physician declined the offer. A somewhat lower proportion of self-referrals turned out to be ineligible for PrEP than physician referrals, showing that people who self-refer generally have a good idea of their eligibility; reasons for non-eligibility included not being at risk of HIV for the previous three months and testing HIV positive.
Self referrals were more likely to be white, had a higher educational level, and were both more likely to have a high level of sexual risk and to regard themselves as being at risk.
Fifty-three per cent of those initially referred/self-referred, and 60% of those eligible, eventually started taking PrEP. Participants in San Francisco were more likely to meet eligibility criteria than others, but also more likely to decline an offer of PrEP, with 62% of those eligible turning it down; conversely, participants in Miami were considerably more likely to turn out to be ineligible, largely because they did not fall within risk criteria, but were very much more likely to take up PrEP if it was offered, with only 22% of those eligible turning it down.
Participants in general averaged 32 years of age, with 20% of them under 25 and 18% over 45. Forty-eight per cent were white, and 35% Latino, with a surprisingly small 8% being black, though this may change as the Washington DC site recruits more participants. Forty-two per cent had no health insurance.
Miami trial participants were younger than participants in San Francisco or Washington, more likely to be Latino or African-American, less likely to be insured, and less likely to report drug use or unprotected receptive anal sex in the prior three months. They were also much less likely to self-refer, but were 50% more likely to end up taking PrEP after initially being referred by physicians than San Franciscans.
The researchers commented on the low levels of uptake among black men and transgender women (there were only a handful of the latter in the study).
"Relatively few transgender women and MSM of color were assessed for participation and enrolled in this study," the researchers comment.
"Additional strategies to increase community awareness of PrEP and engage these populations in PrEP programs are urgently needed."
Drug levels and adherence
The most interesting results from this interim analysis, however, were probably the adherence figures, as determined by drug-level testing in a randomised selection of about a third (196) of the volunteers.
However, there were very different adherence patterns between the three cities.
In San Francisco the majority of volunteers (52%) had tenofovir levels consistent with daily dosing. In Washington DC, however, only just over a third (35%) did and in Miami only 13.5% did.
However, another 43% in both Miami and Washington, and 40% in San Francisco, had levels consistent with taking four doses a week or thereabouts. This dose, while not recommended, has been calculated by the iPrEx study researchers as being about 96% (minimum 90%) effective. Ninety-two per cent of San Franciscans, 78% of people from Washington, and 57% of those from Miami appeared to be taking above this dose.
This left 27% of those from Miami, 18% from Washington and 4% from San Francisco taking about two doses a week, which may offer something in the region of 70% protection; 11%, 2% and 4% respectively taking about one dose a week, which may offer very little protection; and 4.5%, 2% and none who had no detectable tenofovir in their blood at all. Timing of doses clearly matters too: if someone is taking PrEP on two days a week, it matters on which days and whether their exposures to HIV happen the day after or four days after they take PrEP.
Clearly, however, some participants are taking PrEP at times of their own choice and, if the Miami results are reproduced elsewhere, sub-optimal adherence is not always associated with lower motivation to take PrEP. It may be more to do with differences in knowledge, convenience and lifestyle.
Cohen SE et al. Implementation of PrEP in STD Clinics: High Uptake and Drug Detection Among MSM in the Demonstration Project. 21st Conference on Retroviruses and Opportunistic Infections (CROI), abstract 954, 2014.