The World Health Organization (WHO) has endorsed the on-demand, or 2-1-1, pre-exposure prophylaxis (PrEP) dosing protocol for men who have sex with men (MSM) just as a new French study has provided a more in-depth comparison of the daily versus on-demand PrEP regimens, aidsmap reports.
The on-demand dosing protocol involves taking a double dose of Truvada (tenofovir disoproxil fumarate/emtricitabine) two to 24 hours before expected sex. Then, if sex occurs, a single dose should follow the double dose by 24 hours and then one last single dose should be taken 24 hours after that. If sex ultimately occurs on consecutive days, individuals should continue taking one Truvada tablet daily until 48 hours have passed since the last sex act.
The WHO recommendation was announced at the 10th International AIDS Society Conference on HIV Science (IAS 2019) in Mexico City along with new findings of the French Prévenir study comparing on-demand PrEP with the daily PrEP protocol. Led by Jean-Michel Molina, MD, of the Hôpital Saint-Louis in Paris, the study followed his previous IPERGAY study of on-demand PrEP and, as of May 2019, had enrolled 3,057 men at 26 sites in Paris.
Molina was among those who developed the WHO recommendation for on-demand PrEP.
At the 9th International AIDS Society Conference on HIV Science (IAS 2018) in Amsterdam, Molina presentedinitial findings of Prévenir, which at the time had seen no new HIV infections among its participants. In his Mexico City conference update, he reported two seroconversions in the study.
Eighty-five percent of the participants were white. The median age was 36 years old. Thirty individuals were heterosexual, 13 were transgender women and the remainder were MSM. The majority said they did not have a regular sexual partner.
Upon entering the study, the participants reported a median of 10 sexual partners during the previous three months and a median of two acts of condomless sex during the past month. Fourteen percent reported using recreational drugs when they last had sex, known in Europe as chemsex.
The Prévenir participants were given the option of taking Truvada daily or according to the on-demand protocol and could switch back and forth between the two dosing protocols. Upon joining the study, about half chose on-demand PrEP; throughout the study, an even proportion followed either dosing protocol. About 15% switched regimens during the study.
At the study visits, men taking PrEP daily reported taking Truvada as directed the last time they had sex in 97% of cases among those following the daily dosing schedule and 82% of the time among those observing the on-demand protocol. The men who did not follow their dosing protocol most commonly reported that they perceived the sex they had had at the time as low risk. At about 20% of the clinic visits in each group, participants said they used a condom the last time they had intercourse.
Two men who had opted to take PrEP on demand contracted HIV during the study. Both men reported that they had stopped taking Truvada several weeks before testing positive for the virus and that in the meantime they had engaged in condomless sex. This meant that the diagnosis rate per 100 cumulative years of follow-up was 0.09 cases in Prévenir as a whole, zero cases among those in the daily PrEP group and 0.2 cases in the on-demand group.
Molina estimated that the study had prevented 143 new cases of HIV.
Those in the daily PrEP group reported a higher number of sex acts and sexual partners compared with those in the on-demand group. In overall study cohort, the frequency with which participants engaged in sex increased by 43% after entering the study before plateauing. The number of reported recent sexual partners declined by 20% after participants went on PrEP.
Compared with the diagnosis rate seen when the participants entered the study, the sexually transmitted infection (STI) rate increased by 38% at month 18, reaching 86 diagnoses per 100 cumulative years of follow-up. At the study’s outset as well as at month 18, STIs were more common among those in the daily PrEP group.
Nine people taking PrEP daily and 11 following the on-demand protocol contracted hepatitis C virus (HCV) during the study. One person each contracted hepatitis A, B and E viruses (HAV, HAB and HEV). This translated to an overall viral hepatitis infection rate of 1.04 cases per 100 cumulative years of follow-up.
As for the WHO recommendation, it followed a 2015 vote of confidence for daily PrEP. The new advisory indicates that on-demand PrEP is an option for MSM, including those who would find the dosing strategy more effective and convenient, those who have less frequent sex and those who can anticipate sex with at least two hours to spare. The recommendation does not apply to any other sex or gender identity, about whom more research regarding the on-demand strategy’s use is needed.
To read the conference abstract, click here.
To read the aidsmap article, click here.
To read the WHO report, click here.