Increasing prescription of pre-exposure prophylaxis (PrEP) is imperative to ending the HIV epidemic in the United States. The objective of this review was to identify health care provider barriers to PrEP implementation. A systematic review was conducted in February 2019 using PubMed to identify barriers to PrEP prescribing practices in the United States. Targeted search terms surrounding PrEP and providers resulted in 222 original studies, 28 of which were ultimately included in our review, with data collected between 2011 and 2018. Six themes were identified across reviewed studies: (i) a lack of PrEP knowledge, (ii) the presence of the Purview Paradox, which refers to discordance in beliefs between HIV specialists and primary care providers on who should prescribe PrEP, (iii) concerns about PrEP costs, (iv) concerns about behavioral and health consequences, (v) interpersonal stigma, and (vi) concerns about patient adherence. A majority of providers were lacking knowledge regarding PrEP, resulting in discomfort in prescribing PrEP, or limited awareness and understanding of PrEP clinical guidelines. Discrepant opinions were identified regarding whether PrEP was best managed within primary care or specialty clinics. Other barriers included concerns about cost, patient adherence, and follow-up maintenance care. Finally, concerns about risk compensation and discomfort discussing sexual activities with patients who would benefit most from PrEP were apparent. Additional work is needed to prepare providers to prescribe and manage patients on PrEP, optimize PrEP delivery, and reduce provider bias. Future research is needed to identify providers’ attitudes and beliefs regarding innovations in PrEP dosing, task shifting, and novel strategies for PrEP care.

HIV pre-exposure prophylaxis (PrEP) is highly effective at preventing HIV; however, PrEP use among transgender individuals remains low. We conducted a systematic review to identify barriers and facilitators to PrEP uptake, adherence, and persistence among transgender individuals in the United States. We conducted a literature search in PubMed and CINAHL databases in March 2021 and followed PRISMA guidelines. Studies were eligible if they were published in a peer-reviewed journal and reported interest, uptake, adherence, and/or persistence of PrEP use among transgender individuals. Articles that did not disaggregate results for transgender participants were excluded. Data from included articles were coded using content analysis and narratively synthesized using a framework matrix. We screened 254 unique articles published after US Food and Drug Administration approval of PrEP, and 33 articles were included in the review. Five themes were identified in the literature, including (1) PrEP concentrations were lower among individuals taking feminizing hormones, but the difference did not appear clinically significant; (2) concerns regarding interactions between gender-affirming hormone therapy and PrEP remain a large barrier; (3) PrEP initiation may facilitate increased self-advocacy and self-acceptance; (4) lack of trust in medical institutions impacts PrEP uptake; and (5) social networks have a significant influence on PrEP knowledge, interest, and adherence. Additional research is needed involving transgender men and nonbinary persons, and efforts to improve PrEP persistence among the transgender community are needed. Training health care providers to provide inclusive and affirming care is perhaps one of the strongest areas for intervention to increase PrEP uptake and persistence.