By testing participants’ blood for the presence of PrEP drugs, researchers have attempted to estimate the number of PrEP doses they have actually taken. They have then looked at the number of HIV infections in people with different levels of adherence.

For example, in the iPrEX OLE study of men who have sex with men and transgender women most infections occurred in people taking less than two doses a week, with none occurring in individuals taking four or more doses. The researchers calculated the following levels of protection:

• Less than two doses a week: 44% fewer infections (credible range: -31 to 77%)

• Two or three doses a week: 84% fewer infections (credible range: 21 to 99%)

• Four or more doses a week: 100% fewer infections (credible range: 86 to 100%).

These results are relevant to HIV exposure during anal sex, but not vaginal sex. Moreover, there are limitations to the methods used to produce these estimates, so they should be treated with caution. In particular, note that the ‘true’ figure for the reduction in infections associated with four or more doses could be as low as 86%. It is not necessarily 100%.

But in practical terms, adherence is most important during periods of exposure to HIV. If an individual knows for sure that they are not going to have sex for a period of time, or not with anyone who could expose them to HIV, then they may prefer to stop taking PrEP during that period. However, it may take several days after PrEP is resumed for protective concentrations to build up in tissues.

Factors associated with good adherence in studies include older age, higher levels of education, perceiving oneself to be at risk of HIV infection and having a higher level of sexual activity. While high-quality adherence counselling is probably helpful, we know little about which approaches are most effective.

Almost all PrEP studies, including PROUD, asked participants to take PrEP every day. But one study has shown that PrEP pills can also be very effective when people only take it before and after they have sex. This is sometimes known as ‘intermittent’ dosing or ‘event-driven’ dosing.

In the IPERGAY study, participants were told to take a double dose of Truvada (two pills) from 2-24 hours before anticipated sex, and then, if sex happened, two separate doses in each of the two days that followed.

The study was conducted in France and Canada, recruiting 400 men who have sex with men. As with the PROUD study, many had multiple sexual partners and were at higher risk of HIV infection than many other gay men.

The rate of new HIV infections was 0.9% in the PrEP group and 6.8% in the placebo control group, with the difference translating to an effectiveness of 86% (credible range: 39 to 98%). Extraordinarily and coincidentally, this was the same level of effectiveness as seen in PROUD.

The study demonstrates that good adherence to intermittent PrEP is possible and that it can be as effective as daily PrEP. The researchers calculated that 18 men needed to take PrEP to prevent one HIV infection in a year.

Some participants had sex quite frequently and were therefore taking PrEP on an almost daily basis. A minority of participants only took a handful of pills a month, either because they were not having much sex or because they had poor adherence.

An intermittent dosing schedule could be given as an option in future UK clinical guidelines. The approach may make adherence easier for some people, particularly those who have a good idea when they are likely to have sex. (For example, this is the case for some people who use dating apps.) But personal preferences vary – other people may find the routine of daily PrEP easier to remember.

With fewer overall doses, any missed doses will matter far more than in a daily regimen.

As fewer pills are taken, an intermittent approach is likely to be cheaper. For the same reason, it might reduce side-effects.

A study in Thailand, South Africa and the United States is trying to find out which dosing schedules are easiest to adhere to. Some participants take PrEP daily, others follow a schedule similar to the IPERGAY study, while in a third group participants are asked to take PrEP twice a week plus an additional dose within two hours of having sex. Full results will be announced soon.