WHO recommends option of event-driven PrEP for gay men

The World Health Organization (WHO) has updated its guidelines for oral pre-exposure prophylaxis (PrEP) in men who have sex with men to include ‘event-driven PrEP’ (ED-PrEP) in addition to daily PrEP.

In a new technical brief entitled What’s the 2+1+1? released at the 10th International AIDS Society Conference on HIV Science (IAS 2019) in Mexico City in July, the WHO acknowledges the mounting evidence for the effectiveness of PrEP taken before and after sex to prevent HIV in gay men.

France and the USA already have guidance for ED-PrEP, while Belgium, the Netherlands and the UK are implementing it via demonstrations projects and trials.

Informing the new WHO guidance, trial results from Prévenir, an ongoing observational study sponsored by the French research agency l’Agence française de recherche sur le sida (ANRS), were presented at IAS 2019.

The research followed 3,000 HIV-negative men on PrEP, with 49% choosing ED-PrEP and 51% choosing daily PrEP. By the end of the trial, only two HIV infections in men taking ED-PrEP had occured. These two men had both discontinued PrEP before the time of their infection.

While the WHO uses the term event-driven PrEP, other terms used include “on-demand”, “non-daily”, “event-based”, “pericoital”, “intermittent” PrEP and “2+1+1”. The latter describes the dosing schedule of ED-PrEP, which consists of the use of a double dose (two pills, which serves as the loading dose) of tenofovir (TDF) plus emtricitabine (FTC) or lamivudine (3TC) between two and 24 hours in advance of sex; then, a third pill 24 hours after the first two pills, and a fourth pill 48 hours after the first two pills.

Other regimes have been studied, including the use of only a single pill before and after sex, or taking PrEP four times per week, but so far their efficacy is not known.

In their endorsement, the WHO notes that ED-PrEP should be considered for men who would find it more effective and convenient. This includes men who have infrequent sex (for example, sex less than two times per week on average), or among men who can plan for sex at least two hours in advance, or who can delay sex for at least two hours.

Importantly, the guidance does not recommend ED-PrEP for women, transgender women, or men who have vaginal and/or anal sex with women, as there is inadequate research particularly around the dosing schedule of ED-PrEP in these groups.

For cisgender women, tenofovir may not reach sufficient levels in the genital tract during ED-PrEP in order to prevent HIV. Whereas in trans women, feminizing hormonal drugs have been shown to have a small effect on tenofovir concentration levels in the blood. This is not an issue for daily PrEP, but may be for ED-PrEP.