Participants, of both sexes, had an average age of 32. In terms of ethnicity, 23 where white, 11 black African and two of other ethnicity.
Drug levels of raltegravir in rectal fluid were about one milligram per millilitre: this is a high level, so high that Julie Fox commented that it was theorised that it could have been just unabsorbed drug passed through the gut. However, these levels persisted for at least two days after stopping the drug, suggesting cellular absorption. Levels in vaginal fluid were about 100 times lower.
Levels of lamivudine in the rectum were even higher than that of raltegravir, but fell somewhat more quickly, whereas levels in the vagina were only ten times lower than in the rectum, but persisted for at least five days after PrEP was stopped.
The explant assays showed that raltegravir alone was 70-80% protective – slightly more so, in fact, to vaginal cells – and that protection persisted for at least three days after PrEP was stopped.
Adding in lamivudine, however, raised protection to 100%. In rectal cells, this had happened by day two and stayed at 100% while PrEP was taken, falling to 80% four days after PrEP was stopped. In the vagina, protection was only 65% at day two but had built up to 100% by day eight – and was still 100% protective at day 12. Drug levels in the rectum were correlated with protection, but drug levels in the vagina were not, leading Dr Fox to comment that we still do not fully understand how PrEP protects on a molecular level.
These tissue levels and the levels of protection seen – with a fast build-up in the rectum and a slower one in the vagina – are similar to studies of tenofovir/emtricitabine PrEP. Like them, it suggests that raltegravir/lamivudine PrEP could work with event-based dosing for gay men, but that daily PrEP would be needed for women, with a week to achieve full protection.
The study also provides valuable evidence that lamivudine is indeed likely to work just as well as emtricitabine if used in PrEP.