Strengths & limitations
This study had several strengths. First, this is the first study to examine the safety and acceptability of and adherence to these three promising modalities for rectal drug delivery prior to RAI. Examining each product’s use in real life contexts strengthens the social validity of our findings and the potential use for these three modes of delivery in the future. Second, the crossover randomized design of our trial allowed us to assess SGM participants’ acceptability of and adherence to these three modalities within the same trial, offering a unique opportunity to compare their acceptability, safety, and adherence within individuals who used all three products prior to RAI. Third, given the variability in both legal protections and social acceptance of SGM people between and within these countries, our ability to recruit and retain a large sample of young SGM living in geographically and socio-politically diverse countries is noteworthy and strengthens the generalizability of our findings to diverse contexts. Finally, our efforts to minimize the impact of the COVID-19 pandemic during our data collection period minimized interruptions to our trial and ensured that rigor was preserved [Nonetheless, our trial also had several limitations. First, self-reported responses tend to be favorable due to social desirability; however, we tried to minimize bias by having participants complete their questionnaires in a private location during their clinical visits. Second, there is a possibility of recall bias when participants completed their surveys. Third, we recruited a convenience sample of participants willing to use each of the study products at least once per week, as required by the protocol. We acknowledge that the generalizability of our clinical trial findings may not be representative of all individuals practicing RAI. Fourth, given the placebo nature of the three products used in our trial, we were unable to employ a biological confirmation method regarding participants’ product use and adherence, or examine the extent and duration of rectal coverage afforded by each product during and after sex. These data will be crucial in the future, particularly as drug candidates are embedded into these modalities and tested for safety and adherence. Fifth, we were unable to recruit the sexual partners of our study participants. Given existing data regarding partners’ roles in young SGMs’ decision-making when selecting HIV prevention strategies prior to sex, future research examining these dyadic dynamics may be warranted. Finally, while we designed our clinical trial to resemble participants’ product use to as close as ‘real-world’ settings possible while maintaining rigor, we acknowledge that the trial protocols may hinder the social validity of the findings. Future research examining these products in real-world situations may further clarify their potential for use as rectal microbicide modalities.