This article by Gus Cairns first appeared on aidsmap.com here. Republished with permission.
A study in which a group of HIV-negative gay and bisexual men from New York were asked to predict each day whether they would have sex the following day, and then compared their prediction with what actually happened, found that men generally overestimated the likelihood they would have sex.
The only time men accurately predicted whether they would have sex the next day was in the days they predicted it was very unlikely: if men reported that there was only a zero to 5% chance of sex the following day then, sure enough, only about 4% actually ended up having sex and there was no case in which someone had sex after having predicted that there was zero chance of them having sex the following day. The sexual optimists, on the other hand, were often disappointed: only 45% of men who predicted a 90% chance of sex the following day actually ended up having it.
In this study, 92 gay men and other men who have sex with men (MSM) from New York aged over 18 were asked to keep online sexual diaries every day for 30 days. The mean completion rate was 78%. The men were asked to say whether they had had sex (where sex meant “anal intercourse with a casual partner”) and also rate the likelihood, from zero to 100%, that they would also have anal sex with a casual partner the following day.
This was a very mixed group of MSM. Their mean age was 33 but a quarter were under 22 and a quarter over 44; 54% were white, 14% black and 14% Latino; 16% defined as bisexual, rather than gay; roughly equal proportions were in full-time work, part-time work and unemployed/student; and two-thirds had been to university. Only one in six had a current steady relationship. Fifty-nine per cent reported they had sex on three or more days per week.
Although there was a correlation between the prediction of sex and its occurrence, the men were in general more likely to overestimate rather than underestimate their chances of casual sex the following day. If men said they thought there was a 100% chance of sex the following day, only 58% actually had it: if a 50% chance, only 20% had it; if a 20% chance, only 10% had it. Only if men rated their chances of sex as very low were their forecasts accurate: for instance, where men rated their chances as 1-10%, about 5% had sex, and if they thought there was no chance, they did not end up having sex.
Implications for PrEP regimens
The researchers comment that these findings have implications for studies of intermittent PrEP: while so far intermittent-PrEP studies have tended to instruct participants to take PrEP if they think they are likely to have sex the next day, it might be safer, and in certain situations more cost-effective, they comment, to tell participants: “take PrEP daily unless you are definitely not going to have sex tomorrow; then you can miss a dose.”
This strategy would have to be quite strict, however. Although participants generally overestimated their chances of having sex, when the researchers ‘worked backwards,’ i.e. looked at occasions of sex and then looked at whether participants had predicted it, they found a number of ‘false negatives’: cases where people had ended up having sex even though they had rated the probability as low.
This means that, if a group of gay men similar to those in this study were told to take PrEP if they thought they would have sex, there was a substantial number of ‘false positives’, to the extent that only 20% of PrEP doses taken would actually being needed. However 3.8% of occasions of sex would be ‘false negatives’, i.e. not covered by PrEP. There were only no ‘false negatives’ if participants were absolutely certain they would not have sex the following day.
Given that, while ‘false positives’ only waste money, but a ‘false negative’ may end up with an HIV infection, the researchers recommend that the safest advice would be to advise PrEP takers that they can skip a dose only if there is “no chance” they will have sex the following day.
While most studies of pre-exposure prophylaxis (PrEP) have involved taking a daily dose of antiretroviral drugs to prevent HIV, some studies have looked at, and are looking, at intermittent dosing of one sort or another. Intermittent dosing may lower the possibility of side-effects, but the main motive for investigating it is cost: with each Truvada (tenofovir/emtricitabine) pill in the US costing $25.86 (£17), the researchers estimate, it could save $4700 a year per person (£3110) if people took PrEP only every other day, or only 50% of the time.
Recently the French IPERGAY study, which randomised gay men to take two Truvada or placebo pills 2-12 hours before they anticipated sex, and then to take two more in the two days after sex if it actually happened, stopped its randomised phase because of higher-than-expected effectiveness. Data on adherence shows that the amount of drug used in IPERGAY was about 50% of what would be used with full adherence to daily dosing.
An ongoing international study, HPTN067 (ADAPT), randomises participants to three different regimens: daily PrEP; PreP twice a week regardless of the chance of sex, with an extra post-exposure dose if sex occurs (time-driven); or one dose of PrEP 24 hours before anticipated sex, followed by one post-exposure dose two hours after sex (event-driven). This study was closed to follow-up in December and results are expected soon.
Looking at various sexual patterns and comparing them with the ADAPT and IPERGAY intermittent regimens, clearly if men had no sex one week, money would be saved if PrEP was taken according to either of the event-driven regimens, compared to the time-driven regimen. But if they had sex, the IPERGAY regimen would end up with the highest pill usage because it requires four pills. If there was one occasion of sex in the week, or two on consecutive days, then the ADAPT event-driven regimen would be the most economic with only two pills used; but if there were two occasions of sex separated by a day or more, then the ADAPT time-driven regimen would be as economic as the event-driven regimen.
These results are based on 100% prediction reliability, i.e. that in all event-driven regimens, the participants do end up having sex. However the researchers comment that due to the chance of ‘false negatives’ the IPERGAY protocol may actually be the safest, for two reasons.If men end up having sex more than twice a week, their PrEP coverage in IPERGAY would be at least four doses a week, which is the level that the iPrEx study predicts would be effective. Also, IPERGAY allows them to take Truvada the day on which they anticipate sex, rather than the day before. They thus recommend the ADAPT fixed-dose regimen, with a dose only omitted if there is no chance of sex, for men who have sex no more than once a week on one day or two consecutive days, but the IPERGAY regimen for men who have sex on more than two days a week or on days that are not consecutive.
One major limitation of this study was that it only looked at casual sex, even in the case of the 16% of men who had a steady partner. Men’s ability to predict sex - or to postpone it if PrEP has not been taken – may be greater in situations of sex with a regular partner, and more research is needed on the predictability of sex within regular relationships.
Parsons JT et al. Accuracy of highly sexually active gay and bisexual men’s predications of their daily likelihood of anal sex and its relevance for intermittent event-driven HIV pre-exposure prophylaxis. JAIDS, early online publication: doi: 10.1097/QAI.0000000000000507. 2014.