Barriers and Facilitators Influencing PrEP Uptake Among Men Who Have Sex with Men and Transgender Women in the United States: A Systematic Review.

In the United States, men who have sex with men (MSM) and transgender women (TGW) have high HIV pre-exposure prophylaxis (PrEP) awareness, yet uptake rates remain extremely low. This signifies the presence of certain barriers not yet addressed in policy and practice and facilitators not yet utilized in designing effective interventions. This systematic review used the Gelberg and Andersen Model of Vulnerable Populations as a theoretical framework to explore barriers and facilitators to PrEP uptake among MSM and TGW in the US. We searched PubMed, Embase, CINAHL, and Web of Science in May 2025 to identify eligible studies exploring barriers and/or facilitators to PrEP uptake among MSM and TGW in the US. Studies published in 2012 onward in the English language and particularly focusing on uptake (initiation) met the eligibility criteria. We excluded studies focused on awareness, willingness, adherence, persistence, and other components of the PrEP care continuum. The review was conducted in accordance with the PRISMA 2020 Statement. Barriers and facilitators reported in studies were mapped into the domains of the Gelberg and Andersen model and then narratively synthesized using a thematic approach. Eleven studies (9 qualitative and two mixed methods) met the eligibility criteria. Utilizing the Gelberg and Andersen model, within the predisposing factors domain, three themes emerged, namely (a) PrEP knowledge, health beliefs, and misinformation, (b) stigma, discrimination, and trust, and (c) influence of social environment and lived realities. Within the enabling factors domain, three themes emerged, namely (a) financial access and insurance coverage, (b) healthcare provider and system factors, and (c) addressing specific community needs and systemic vulnerabilities. Finally, within the need factors domain, one theme emerged, namely perceived versus evaluated need for PrEP. Additionally, a sub-group analysis showed that Black and Latino TGW may experience additional barriers to PrEP uptake due to intersecting stigma related to race, sexuality, and HIV and scarcity of culturally competent and gender-affirming care. Also, rural MSM may experience additional barriers due to reliance on urban social networks for information and support because of lack of such networks and support tailored to their geographical location. The findings of this review reveal an intricate interplay between predisposing, enabling, and need factors, which aligning with the observations that although PrEP awareness among MSM and TGW has grown, significant gaps in knowledge and misinformation remain, and uptake remains extremely low. These factors extend beyond general awareness levels and hence must be addressed through policy and practice interventions to enhance HIV prevention efforts among this key population in the US.