A recently-published survey from the US and Canada reveals that on the whole HIV-negative gay men would rather take pre-exposure prophylaxis (PrEP) intermittently and only before they anticipate sex, in what has been called “event-driven2 or “on-demand” PrEP.
The study was conducted in 2011 after the iPrEx study results came out and around the time PrEP received approval from the US Food and Drug Administration, so its results were not influenced by later trial results. It was done in preparation for the ADAPT (HPTN 067) trial of three different PrEP regimens, the first results from which were announced at this year’s IAS conference in Vancouver.
The respondents were asked about event-driven and two other types of PrEP – daily and twice-weekly dosing with an added dose after sex (sometimes called ‘time-driven’ dosing). Although event-driven remained the most popular strategy, the popularity of the other two was affected by how frequently participants had condomless anal sex, and whether it was usually planned or sometimes unplanned.
The study was conducted online and advertised on a popular gay dating site. Of 18,710 men who clicked through to the survey from its ad, 6,993 answered an initial screening questionnaire (designed to weed out HIV-positive, non-US/Canadian and under-18 enquirers); 5,079 enrolled and 3,217 completed all questionnaire items.
The questionnaire asked respondents about the frequency of condomless anal sex and how much of it was “unplanned”. Planned had quite a wide definition and included not only an arranged date but also going to a sex party, bathhouse or bar with the intention of having sex, on the premises or that night. So “unplanned” might be better called “unexpected”.
The average age of respondents was 40, 84% were white, 97% defined themselves as gay and 69% were graduates – illustrating one of the problems of internet surveys, namely that they tend to select whiter, richer and better-educated people than in the general population.
Results showed 46% of respondents had had at least one experience of unplanned condomless sex in the last three months – 8% of respondents were classed as having 2frequent” condomless sex, which was defined as having it at least once a week throughout the last three months. Having unplanned sex was associated with lower education (graduates were 32% less likely to have it) but on the contrary a higher income (men who earned more than $18,000 a year were about 30% more likely to have unplanned sex than lower-income men). It was also associated with identifying as gay rather than bisexual and perceiving oneself at high risk of HIV. It was, as one would expect, associated with generally having condomless sex often (over five times in the last three months) but also with being in a monogamous relationship. Finally, it was also associated with not having had a healthcare appointment in the last year.
Because the “frequent condomless sex” group was smaller, there were fewer clear associations with other factors, but the 8% in this group tended to be younger (1% less likely to be in this group per year older), define themselves as gay, and perceive themselves at higher risk of HIV. It was very strongly associated with being in a monogamous relationship: monogamous men were over four times more likely to be in the “frequent condomless sex” category than anyone else. This probably attests to the adoption of sero-sorting/negotiated safety agreements between long-term partners. There were no associations between depression, or drink and drugs, and the type or frequency of sex.
The survey found that 80% of condomless anal sex was planned or expected. Interestingly, it was not the case that sex was more frequent at weekends and only 14% of respondents only, or generally, had sex at weekends. For condomless sex in general, it was most likely to happen on Thursday, Friday or Saturday, while unplanned condomless sex happened at the same frequency throughout the week except for Sunday or Monday.
The respondents were asked which type of PrEP regimen they felt they would prefer if they took PrEP. The most popular was event-driven PrEP, on the basis of the regimen used in ADAPT (a single dose within 48 hours of anticipated sex and a dose no more than two hours after sex if it happened): 76% of respondents said they would take PrEP on that basis.
The study found 62% said they would take time-driven PrEP, which in ADAPT meant two regular doses a week plus a post-sex dose and 50% said they would take daily PrEP. These results, however, were influenced by whether sex was unplanned, or frequent. While intermittent PrEP remained the most popular choice, men who had frequent condomless sex were 50% more likely to also say they would take daily PrEP, while men who had experienced unplanned sex were 24% more likely to say they would take time-driven PrEP. Meanwhile, those who only had planned sex were 21% more likely to prefer event-driven PrEP than average.
The survey was conducted before the first, adherence results from ADAPT were announced. This international study compared adherence in participants given daily, time-driven and event-driven PrEP in three different cities (gay men in Bangkok and Harlem, New York, and women in Cape Town).
Interestingly, ADAPT found that adherence was inversely proportional to the popularity of the PrEP regimens in this preparatory study. In the trial site with the best adherence, namely in gay men in Bangkok, 85% of sex acts were adequately covered by daily PrEP, 84% by time-driven PrEP, but only 75% by intermittent PrEP. In Harlem, among largely poorer black gay men, 66% of acts were covered by daily PrEP, 47% by time-driven and 52% by intermittent. It thus appears that the anticipated ease of a PrEP regimen may not in reality be mirrored by the actual ease of taking it.
Nonetheless in the Ipergay study only 43% of participants took the full amount of PrEP, according to protocol, every time they had sex, and yet Ipergay achieved 86% effectiveness. Drug level studies conducted by the Ipergay researchers indicate that drug levels in most users of intermittent PrEP could be high enough to protect most users, as least in anal sex, as long as adherence does not fall below a certain threshold. However Ipergay had a regimen of two PrEP pills before sex and one in each of the two days after, so the drug exposure was roughly twice that in ADAPT.
Pre-exposure prophylaxis (PrEP), taken as a single daily co-formulated pill containing tenofovir-emtricitabine, is a promising intervention to reduce the likelihood of HIV acquisition in at-risk individuals, including men who have sex with men (MSM). Little is known about the acceptability of less than daily, intermittent PrEP (iPrEP) regimens. We conducted an online survey of North American MSM to characterize their sexual frequency and planning behaviors and correlate these with PrEP dosing preferences. Of the 3,217 respondents who completed the survey, 46% reported engaging in unplanned condomless anal intercourse (CAI) at least once in the prior 3 months and 8% reported engaging in CAI more than once per week. In multivariable analysis, reporting unplanned CAI was associated with lower educational level, identifying as homosexual/gay as compared to bisexual, being in a monogamous relationship, having a higher self-perceived risk of HIV acquisition, higher income, engaging in CAI more than five times in the last 3 months, and not having visited a healthcare provider in the previous year. Frequent CAI (>1x/week) was associated with being younger, identifying as homosexual/gay as compared to bisexual, being in a monogamous relationship, and having a higher self-perceived risk of HIV. Having had only planned sex over the last 3 months was associated with a preference for event-based PrEP, while having frequent or unplanned CAI was associated with a preference for daily or time-driven PrEP regimens, respectively. Our findings suggest that preferences for different PrEP regimens are associated with the sexual frequency and planning behaviors of potential users.