Comparison between daily and on-demand PrEP (pre-exposure prophylaxis) regimen in covering condomless anal intercourse for men who have sex with men in Hong Kong: A randomized, controlled, open-label, crossover trial

Introduction Both daily and on-demand regimens have been proven effective for pre-exposure prophylaxis (PrEP) against HIV in men who have sex with men (MSM). We aimed to compare the two regimens on their coverage of condomless anal intercourse (CLAI) in MSM. Methods A randomized, controlled, open-label, crossover trial was conducted in a teaching hospital in Hong Kong. Participants were sexually active HIV-negative MSM aged 18 years or above with normal renal function and without chronic hepatitis B infection. Oral tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (TDF/FTC) tablets were prescribed for PrEP. After a 2-week lead-in with daily TDF/FTC for treatment-naive MSM for tolerance assessment, participants were randomly assigned in a 1:1 ratio with a block size of four to either daily-first or on-demand-first arm based on the IPERGAY study, for receiving PrEP for 16 weeks, then crossed-over to the alternative regimen for another 16 weeks. The primary outcome was the proportion of days with PrEP-covered CLAI by intention-to-treat analysis. The trial is registered with the CCRB Clinical Trials Registry, CUHK, CUHK_CCRB00606, and is closed to accrual. Results Between 25 August 2018 and 23 March 2019, 119 eligible participants were assigned to daily-first arm (n = 59) and on-demand-first arm (n = 60) with an 87% overall completion rate (n = 103). With 96% and 54% of days on PrEP during daily and on-demand periods, respectively, the proportion of days with PrEP-covered CLAI between two arms were not statistically different (92% vs. 92%, p = 0.93). About half (47%) were diagnosed with at least one episode of incident sexually transmitted infection. Mild and time-limited adverse events, including diarrhoea, headache, nausea and dizziness, were reported in 37 (31%) and 10 (8%) during the daily and on-demand periods, respectively. At the end of the study, a similar proportion favoured daily or on-demand regimen. Conclusions High prevention-effective adherence, as reflected from the coverage of CLAI, was achievable by either daily or on-demand PrEP among MSM, albeit a higher number of tablets taken for daily PrEP. As both regimens were well accepted, a flexible approach adopting either or both regimens with possible switching is warranted in order to suit individual health needs.