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 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 two to twelve
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.