Discussion
enema, flatulence, diarrhea
EVENTS
RMs are needed for individuals with an increased chance of acquiring HIV through RAI, particularly young SGM across the globe [All three administration modalities with placebo products were found to be safe for use, with less than 20% of AEs deemed related to the study products/modalities and only two related events being graded as having moderate clinical severity or higher. These findings align with our study hypothesis. The safety profile of all three administration modalities with placebo products is promising and underscores the potential of all three modalities as viable for rectal drug delivery. The low incidence of distinct product-related AEs (e.g., diarrhea, flatulence) across study products is also noteworthy, as it mirrors common AEs reported when using over-the-counter rectal products (e.g., enemas) and prior rectal microbicide candidates in clinical trials (e.g., gels). while we should continue to reduce the occurrence of any AEs during product development, the promising safety profiles for the three modalities using placebo products employed in this trial offer a threshold whereby future clinical trials examining these same modalities with active drug ingredients can benchmark their safety endpoints.Consistent with our hypotheses for our acceptability and adherence endpoints, SGM participants reported high overall acceptability for all three products and high overall adherence per protocol and per RAI act. While survey research literature has noted high hypothetical acceptability to RMs as an HIV prevention strategy prior to RAI [While overall acceptability and adherence were high for each product, we observed differences in acceptability and adherence after SGM participants had used all three modalities. While the products were rated similarly in their acceptability and there were no differences based on participants’ assigned product sequence, adherence to the enema was higher when compared to the fast-dissolving insert or the suppository. Given the high prevalence of rectal douching prior to RAI among SGM globally [We also observed differences for both acceptability and adherence between participants living in the different communities across the five countries participating in the trial. Compared to San Francisco, participants in the other regions reported greater acceptability of the three rectal modalities under study. Consistent with prior research with hypothetical and real-world studies with rectal candidates [