Barriers to Pre-Exposure Prophylaxis (PrEP) use for HIV: an integrative review

an integrative literature review, using the MEDLINE/PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Academic Search Premier and Scopus (Elsevier) databases.

Results:

all (100%) the articles included identified that PrEP users experience some type of structural barrier related to health services such as long distance from the units, suboptimal logistics for taking pills and professional resistance to prescribing PrEP. Furthermore, 63.21% identified social barriers, such as stigma about sexuality and HIV, in addition to individual barriers such as alcohol use, adverse effects, and concerns about long-term toxicity.

Conclusions:

the barriers to PrEP use are multifactorial. Effective interventions are needed to support PrEP users in accessing, complying with, and retaining health services.

Descriptors:
Pre-Exposure Prophylaxis; Anti-HIV Agents; Prevention and Control; Access to Health Services; Sexual Health

Database	Search strategy
MEDLINE /PubMed	#1 (pre-exposure prophylaxis OR “PrEP” OR “Pre Exposure Prophylaxis” OR “Pre-Exposure Prophylaxi” OR “Prophylaxis, Pre-Exposure” OR “Pre-Exposure Prophylaxis (PrEP)” OR “Pre Exposure Prophylaxis (PrEP)” OR “Pre-Exposure Prophylaxi (PrEP)” OR “Anti-HIV Agents” OR “Agents, Anti-HIV” OR “Anti HIV Agents” OR “Anti-AIDS Agents” OR “Agents, Anti-AIDS” OR “Anti AIDS Agents” OR “Anti-HIV Drugs” OR “Anti HIV Drugs” OR “Drugs, Anti-HIV” OR “AIDS Drugs” OR “Drugs, AIDS” OR “Anti-AIDS Drugs” OR “Anti AIDS Drugs”)
	#2 (HIV Infection [MeSH] OR HIV [MeSH] OR “Human Immunodeficiency Virus” OR “Immunodeficiency Virus, Human” OR “Immunodeficiency Viruses, Human” OR “Virus, Human Immunodeficiency” OR “Viruses, Human Immunodeficiency” OR “Human Immunodeficiency Viruses” OR “Human T Cell Lymphotropic Virus Type III” OR “Human T-Cell Lymphotropic Virus Type III” OR “Human T-Cell Leukemia Virus Type III” OR “AIDS Virus” OR “AIDS Viruses” OR “Virus, AIDS” OR “Viruses, AIDS”)
	#3 (medication adherence [MeSH] OR treatment adherence and compliance [MeSH] OR “Drug Adherence” OR “Adherence, Drug” OR “Medication Nonadherence” OR “Nonadherence, Medication” OR “Medication Noncompliance” OR “Noncompliance, Medication” OR “Medication Non-Adherence” OR “Medication Non Adherence” OR “Non-Adherence, Medication” OR “Medication Persistence” OR “Persistence, Medication” OR “Medication Compliance” OR “Compliance, Medication” OR “Medication Non-Compliance” OR “Medication Non Compliance” OR “Non-Compliance, Medication” OR “Drug Compliance” OR “Compliance, Drug” OR “Therapeutic Adherence and Compliance” OR “Treatment Adherence” OR “Adherence, Treatment” OR “Therapeutic Adherence” OR “Adherence, Therapeutic”)
	#4 (health services accessibility [MeSH] OR “Health Services Availability” OR “Accessibility of Health Services” OR “Accessibility, Health Services” OR “Access to Health Services” OR “Access to Health Care” OR “Access to Therapy” OR “Access to Therapies” OR “Therapy, Access to” OR “Access to Treatment” OR “Access to Treatments” OR “Treatment, Access to” OR “Health Services Geographic Accessibility” OR “Program Accessibility” OR “Accessibility, Program” OR “Access To Medicines” OR “Access To Medicine” OR “Access to Medications” OR “Access to Medication” OR “Medication, Access to” OR “Medication Access” OR “Access, Medication”))
	#1 AND #2 AND #3 AND #4
CINAHL	(pre-exposure prophylaxis or prep or preexposure prophylaxis) OR HIV pre exposure prophylaxis AND (healthcare or health care or hospital or health services or health facilities) AND (barriers or obstacles or challenges) AND (patient compliance or patient adherence)
Academic Search Premier	(pre-exposure prophylaxis or prep or preexposure prophylaxis) OR hiv pre exposure prophylaxis AND ( healthcare or health care or hospital or health services or health facilities ) AND ( barriers or obstacles or challenges ) AND ( patient compliance or patient adherence )
SCOPUS	(TITLE-ABS-KEY(“pre-exposure prophylaxis”) AND TITLE-ABS-KEY (“HIV”) AND TITLE-ABS-KEY (“Health Services Accessibility”) OR TITLE-ABS-KEY (“medication adherence”) OR TITLE-ABS-KEY (“treatment compliance”)) AND (LIMIT-TO(PUBYEAR, 2021) OR LIMIT-TO PUBYEAR, 2020) OR LIMIT-TO (PUBYEAR, 2019) OR LIMIT-TO (PUBYEAR, 2018) OR LIMIT-TO (PUBYEAR, 2017) OR LIMIT-TO (PUBYEAR, 2016) OR LIMIT-TO (PUBYEAR, 2015) OR LIMIT-TO (PUBYEAR, 2014) OR LIMIT-TO (PUBYEAR, 2013) OR LIMIT-TO (PUBYEAR, 2012) OR LIMIT-TO (PUBYEAR, 2011)) AND ( LIMIT-TO(DOCTYPE, “ar”))

Authors, year and country of study	Objective of study	Population/sample studied	Method/strategy used	Main findings	LoE^* * LoE - level of evidence.
Arnold et al., 2017(¹⁸18 Arnold T, Rubisten LB, Chan PA, Brumer AP, Bolonha ES, Beauchamps L, et al. Social, structural, behavioral and clinical factors influencing retention in Pre-Exposure Prophylaxis (PrEP) care in Mississippi. Plos One. 2017;12(2):e0172354. https://doi.org/10.1371/journal.pone.0172354 https://doi.org/10.1371/journal.pone.017... )/ USA	Explore the structural, social, behavioral and clinical factors that affect PrEP use and retention in care.	Young MSM (n=30)	Qualitative/individual interviews	The main factors that affect PrEP use and retention in PrEP care include structural factors (cost, assistance with doctor visits and drug payments), HIV stigma and relationship status, partner’s HIV status, risky sexual behaviors and clinical factors (side effects).	V
Ellison et al., 2019(²⁰20 Ellisson J, Berg JJVD, Montgomery MC, Tao J, Pashankar R, Mimiaga MJ, et al. Next-Generation HIV Pre-Exposure Prophylaxis Preferences Among Men Who Have Sex with Men Taking Daily Oral Pre-Exposure Prophylaxis. AIDS Patient Care STDS. 2019;33(11):482-91. https://doi.org/10.1089/apc.2019.0093 https://doi.org/10.1089/apc.2019.0093... )/ USA	Assess barriers to oral PrEP and influences of sociodemographic characteristics and sexual behavior in choosing new drug formulations.	MSM (n=108)	Quantitative, cross-sectional/individual interviews	The listed barriers were daily PrEP regimen, difficult access to PrEP prescribers, difficulty making appointments, picking up prescriptions and talking to health professionals prescribing PrEP, racial and ethnic differences (Black and Hispanic men face more barriers compared to white and Asian men).	IV
Hunt et al., 2019(²¹21 Hunt T, Lalley-Chareczko L, Daughtridge G, Swyryn M, Koenig H. Challenges to PrEP use and perceptions of urine tenofovir adherence monitoring reported by individuals on PrEP. AIDS Care. 2019;31(10):1203-6. https://doi.org/10.1080/09540121.2019.1587369 https://doi.org/10.1080/09540121.2019.15... )/ USA	Examine the challenges of accessing and complying with PrEP and to assess the usefulness of objectively monitoring PrEP compliance via urine.	Young adults (aged 18 - 34) using PrEP (n=40)	Quantitative, cross-sectional, descriptive	Participants reported being able to access PrEP quickly, but notable barriers reported included the unwillingness of the provider to prescribe PrEP. Regarding compliance, the most frequent barrier was remembering to take the medication.	V
Park et al., 2019(²²22 Park CJ, Taylor TN, Gutierrez NR, Zingman BS, Blackstocke OJ. Pathways to HIV Pre-exposure Prophylaxis Among Women Prescribed PrEP at an Urban Sexual Health Clinic. J Assoc Nurses AIDS Care. 2019;30(3):321-9. https://doi.org/10.1097/JNC.0000000000000070 https://doi.org/10.1097/JNC.000000000000... )/ USA	Characterize the path to PrEP gathering and continuity.	Black or Latina heterosexual cisgender women (n=14)	Qualitative	Misinformation about PrEP among healthcare professionals, concerns about medication safety, difficulty filling and withdrawing PrEP at pharmacies, out-of-pocket health costs.	V
Rice et al., 2019(²³23 Rice WS, Stringer KL, Sohail M, Crockett KB, Atkins GC, Kudroff K, et al. Accessing Pre-exposure Prophylaxis (PrEP): perceptions of Current and Potential PrEP Users in Birmingham, Alabama. AIDS Behav. 2019;23:2966-79. https://doi.org/10.1007/s10461-019-02591-9 https://doi.org/10.1007/s10461-019-02591... )/ USA	Examine perceptions of access to PrEP.	Men who use PrEP (n=44)	Semi-structured individual interviews	The main barriers were cultural and social norms that silence the discussion about sexuality, lack of awareness and dissemination about PrEP, stigma related to sexuality, concerns about the adequacy and technical quality of PrEP services. The structural ones were long distances from health services, conflicting appointment times, medication costs, lack of health insurance resources, lack of knowledge of PrEP by health professionals, low perceived risk of HIV, concern about side effects.	V
Schwartz et al., 2019(²⁴24 Schwartz J, Grimm J. Stigma Communication Surrounding PrEP: the experiences of a sample of men who have sex with men. Health Commun. 2019;34(1):84-90. https://doi.org/10.1080/10410236.2017.1384430 https://doi.org/10.1080/10410236.2017.13... )/ USA	Better understand the experiences of MSM in the adoption of PrEP.	MSM (n=38)	Qualitative/individual interviews	Stigma about PrEP from the very health professionals who provide PrEP, stigma of health professionals about homosexuality, social stigma about PrEP use being related to promiscuity, perception of discomfort of health professionals in talking about sexual health with gay men.	V
Sun et al., 2019(²⁵25 Sun, CJ, Anderson KM, Bangsberg D. Access to HIV Pre-exposure Prophylaxis in Practice Settings: a Qualitative Study of Sexual and Gender Minority Adults’ Perspectives. J Gen Intern Med. 2019;34:535-43. https://doi.org/10.1007/s11606-019-04850-w https://doi.org/10.1007/s11606-019-04850... )/ USA	Identify barriers and facilitators to accessing PrEP.	Gay and cisgender men (n=27)	Qualitative	Long distances to access PrEP, living in a rural area, difficulty connecting to a PrEP prescriber, costs to buy the drug and interruptions in the supply of PrEP in pharmacies, long distances to access PrEP, living in a rural area, difficulty connecting to a professional PrEP prescriber, costs to purchase the drug, and interruptions in the supply of PrEP at pharmacies.	V
Wood et al., 2019(⁷7 Wood S, Gross R, Shea JA, Bauermeister JA, Franklin J, Petsis D, et al. Barriers and Facilitators of PrEP Adherence for Young Men and Transgender Women of Color. AIDS Behav. 2019;23(10):2719-29. https://doi.org/10.1007/s10461-019-02502-y https://doi.org/10.1007/s10461-019-02502... )/ USA	Identify barriers and facilitators to HIV PrEP compliance.	MSM and trans women (n=31)	Nested mixed method with a prospective cohort	Stigma related to being mistaken for someone with a positive HIV status, HIV-related homophobia, stigma related to skin color, fear of having one’s sexuality revealed to one’s family, inaccessibility of health systems, side effects, stressors related to routine life and low perception of HIV risk.	IV
Laborde et al., 2020(²⁶26 Laborde ND, Kinley PM, Spinelli M, Vittinghoff E, Whitacre R, Scott HM, et al. Understanding PrEP Persistence: provider and patient perspectives. AIDS Behav. 2020;24(9):2509-19. https://doi.org/10.1007/s10461-020-02807-3 https://doi.org/10.1007/s10461-020-02807... )/ USA	Interpret the difficulties in PrEP persistence in a context of structural barriers, as well as clinical, pharmaceutical and interpersonal experiences.	Adult PrEP users (n=25) and health professionals prescribing PrEP (n=18)	Qualitative/individual interviews	Sexuality-related stigma, medical distrust, difficulty meeting PrEP follow-up requirements such as scheduling and attending routine appointments and laboratory tests, housing instability, substance use, mental health, difficulty communicating with providers. Getting refills from pharmacies was inconvenient and alienating for some participants.	V
Nieto et al., 2020(²⁷27 Nieto O, Brooks RA, Landrian A, Cabral A, Fehrenbacher AE. PrEP discontinuation among Latino/a and Black MSM and transgender women: a need for PrEP support services. PLoS One. 2020;15(11):e0241340. https://doi.org/10.1371/journal.pone.0241340 https://doi.org/10.1371/journal.pone.024... )/ USA	Explore reasons for discontinuing PrEP.	Black and Latino MSM and Black and Latino transgender women (n=22)	Qualitative/interviews with a semi-structured script	Lower perceived risk of HIV related to changes in sexual behavior, loss or change of health insurance, long distances to health services, difficulty attending routine appointments, anticipated and experienced adverse medication effects, fear of PrEP interaction with hormones or overloading the body with too many medications.	V
Nieto et al., 2020(²⁸28 Nieto O, Anne EF, Cabral A, Landrian A, Brooks RA. Barriers and motivators to pre-exposure prophylaxis uptake among Black and Latina transgender women in Los Angeles: perspectives of current PrEP users, AIDS Care. 2021;33:244-52. https://doi.org/10.1080/09540121.2020.1769835 https://doi.org/10.1080/09540121.2020.17... )/ USA	Identify barriers and drivers for PrEP adoption.	Black and Latino trans women (n=18)	Qualitative/individual semi-structured interviews	Structural, logistical, linguistic, and cultural barriers to physician engagement, lack of competent transgender care, and prioritization of hormone therapy over PrEP use.
Owens et al., 2020(²⁹29 Owens C, Hubach RD, Williams D, Voorheis E, Lester J, Reece M, et al. Facilitators and Barriers of Pre-exposure Prophylaxis (PrEP) Uptake Among Rural Men who have Sex with Men Living in the Midwestern U.S. Arch Sex Behav. 2020;49:2179-91. https://doi.org/10.1007/s10508-020-01654-6 https://doi.org/10.1007/s10508-020-01654... )/ USA	Raise barriers and facilitators to PrEP use.	MSM and who live in rural areas (n=34)	Quantitative/semi-structured interviews	Lack of rural dissemination of information about PrEP, health professional not informing about PrEP, concern about medication side and adverse effects, cost of PrEP compliance and involvement, lack of access to PrEP care and quality of care, especially in a rural environment.	IV
Camp & Saberi, 2021(³⁰30 Camp C, Saberi P. Facilitators and barriers of 2-1-1 HIV pre-exposure prophylaxis. Plos One. 2021. https://doi.org/10.1371/journal.pone.0251917 https://doi.org/10.1371/journal.pone.025... )/ USA	Understand enablers and barriers to on-demand PrEP use and preferences for PrEP regimens, challenges to PrEP use during the pandemic.	MSM (n=140)	Cross-sectional, quantitative, with online data collection	Unplanned sexual encounters, difficulty remembering the dose, unpreparedness of the professional to provide PrEP care, the COVID-19 pandemic (difficulty in performing/obtaining laboratory tests, having PrEP refills, receiving a refill prescription from a healthcare professional, not being able to get a healthcare professional consultation, and not being able to communicate with your healthcare professional).	V
Felsher et al., 2021(³¹31 Felsher M, Ziegler E, Amico KR, Carrico A, Coleman J, Roth AM. "PrEP just isn't my priority": adherence challenges among women who inject drugs participating in a pre-exposure prophylaxis (PrEP) demonstration project in Philadelphia, PA USA. Soc Sci Med. 2021;275:113809. https://doi.org/10.1016/j.socscimed.2021.113809 https://doi.org/10.1016/j.socscimed.2021... )/ USA	Describe the context of lives of people who use drugs and the challenges of compliance with PrEP.	Cisgender women who inject drugs (n=23)	Qualitative/individual interviews with semi-structured script	Difficulty meeting basic survival needs arising from the intersection of opioid use disorder, economic insecurity and housing instability, forgetting to take medication regularly, lack of secure storage of pills, loss or theft of pills, low self-efficacy, disabling structural factors (prescription drug market, drug treatment facility, or prison facility).	V
Jackson-Gibson et al., 2021(³³33 Jackson-Gibson M, Ezema AU, Orero W, Were I, Ohiomoba RO, Mbullo PO, et al. Facilitators and barriers to HIV pre-exposure prophylaxis (PrEP) uptake through a community-based intervention strategy among adolescent girls and young women in Seme Sub-County, Kisumu, Kenya. BMC Public Health. 2021;21:1284. https://doi.org/10.1186/s12889-021-11335-1 https://doi.org/10.1186/s12889-021-11335... )/ Kenya	Explore enablers and barriers to PrEP implementation, acceptance and persistence.	Adolescent girls and young women (n=40)	Qualitative/individual interviews and focus groups	Side effects (lack of appetite, dizziness, nausea, vomiting, and stomach pains), PrEP-related community stigma, geographic distance to health facility, PrEP use associated with increased promiscuity, commercial sex workers, and people infected with PrEP HIV.	V
Kadiamada-Ibarra et al., 2021(³⁹39 Kadiamada-Ibarra H, Hawley NL, Sosa-Rubí SG, Wilson-Bathers M, Franco RR, Galárraga O. Barreiras e facilitadores para a adoção da profilaxia pré-exposição entre trabalhadores do sexo masculinos no México: uma aplicação da estrutura RE-AIM. BMC Saúde Pública. 2021;21:2174. https://doi.org/10.1186/s12889-021-12167-9 https://doi.org/10.1186/s12889-021-12167... )/ Mexico	Identify barriers and facilitators of a PrEP compliance program.	Male sex workers (n=8)	Quali-quantitative/individual interviews + focus groups	Lack of properly focused strategies to reach male sex workers, stigma related to HIV, PrEP use and key populations, geographic distance from PrEP facilities, lack of information about where to get PrEP and costs, lack of public policy, limitation of PrEP provision at ImPrEP sites and in implementation studies.	V
Kimani et al., 2021(³⁴34 Kimani M, Van Der Elst EM, Chirro O, Wahome E, Ibrahim F, Mukuria N, et al. “I wish to remain HIV negative”: pre-exposure prophylaxis adherence and persistence in transgender women and men who have sex with men in coastal Kenya. Plos One. 2021. https://doi.org/10.1371/journal.pone.0244226 https://doi.org/10.1371/journal.pone.024... )/ Kenya	Explore reasons for PrEP persistence.	Transgender women and men who have sex with men (n=53)	Mixed study/qualitative stage with semi-structured interview	Daily dosing schedule was a nuisance. Withdrawal of 90-day pills, negative reactions from partners and stigmatizing health services were considered barriers.	V
Koppe et al., 2021(³⁸38 Koppe U, Marcus U, Albrecht S, Jansen K. Barriers to using HIV pre-exposure prophylaxis (PrEP) and sexual behavior after stopping PrEP: a cross-sectional study in Germany. BMC Public Health. 2021;21:159. https://doi.org/10.1186/s12889-021-10174-4 https://doi.org/10.1186/s12889-021-10174... )/ Germany	Analyze factors associated with stopping PrEP, barriers that may prevent people from continuing PrEP, and investigate sexual behavior after stopping PrEP.	Adults who used or were using PrEP (n=4,848)	Cross-sectional, quantitative/online data collection	The barriers described are often modifiable. Barriers were referred to as changing sexual partners, satisfaction with other prevention strategies, lower perception of risk of acquiring HIV, side effects, not wanting to take a chemical substance, fear of long-term side effects. Logistical barriers were difficulty obtaining PrEP, difficulty finding a doctor who prescribes PrEP, financial burden, and lack of health insurance coverage.	V
Ogunbajo et al. 2021(¹⁹19 Ogunbajo A, Storholm ED, Ober AJ, Bogart LM, Reback CJ, Flynn R, et al. Multilevel Barriers to HIV PrEP Uptake and Adherence Among Black and Hispanic/Latinx Transgender Women in Southern California. AIDS Behav. 2021;25:2301-15. https://doi.org/10.1007/s10461-021-03159-2 https://doi.org/10.1007/s10461-021-03159... )/ USA	Understand barriers to compliance experienced for PrEP use.	Black and Hispanic/Latino trans women and non-binary individuals (n=30)	Qualitative/individual interview	Concerns about costs, mental health issues, substance use, and concerns about PrEP side effects, including hormone interaction, intimate/romantic partner influence, and the impact of patient-professional communication, stigma, and negative community views related to PrEP, negative experiences in healthcare settings, unreliable transportation, employment, and housing insecurity.	V
O’Rourke et al., 2021(³⁵35 O’Rourke S, Hartmann M, Myers L. The PrEP Journey: Understanding How Internal Drivers and External Circumstances Impact The PrEP Trajectory of Adolescent Girls and Young Women in Cape Town, South Africa. AIDS Behav. 2021;25:10195. https://doi.org/10.1007/s10461-020-03145-0 https://doi.org/10.1007/s10461-020-03145... )/ Cape Town	Explore PrEP use experiences, including compliance and persistence or discontinuation experiences.	Adolescent girls and young women (n=22)	Qualitative prospective cohort	Pill-taking challenges, social opposition, or traumatic/unexpected event. Feelings of disappointment/failure regarding inability to continue PrEP use, PrEP-related stigma, decreased motivation, cultural issues such as conflict with coming-of-age traditions, lack of family support.	V
Sack et al., 2021(³⁶36 Sack DE, Schacht CD, Paulo P, Graves E, Emílio AM, Matino A, et al. Pre-exposure prophylaxis use among HIV serodiscordant couples: a qualitative study in Mozambique. Global Health Action. 2021;14. https://doi.org/10.1080/16549716.2021.1940764 https://doi.org/10.1080/16549716.2021.19... )/ Mozambique	Explore the perspectives, attitudes and experiences of HIV-serodiscordant partners taking PrEP.	People in HIV-serodiscordant relationships (n=19)	Qualitative/individual semi-structured interviews	The factors that influence PrEP compliance were divided into individual, interpersonal and organizational. Individual factors were love for the partner, knowledge about PrEP and belief that the drug is effective, and fear of HIV and PrEP stigma. Interpersonal factors affecting PrEP uptake were desire to protect family, partner support and relationship strength, overcoming fear of stigma to seek support from family and friends, and gender compliance approaches.	V
Stoner et al., 2021(³⁷37 Stoner MCD, Rucinsk KB, Giovenco D, Gill K, Morton JF, Bekker LG, et al. Trajectories of PrEP Adherence Among Young Women Aged 16 to 25 in Cape Town, South Africa. AIDS Behav. 2021;25:2046-53. https://doi.org/10.1007/s10461-020-03134-3 https://doi.org/10.1007/s10461-020-03134... )/ Cape Town	Understand patterns of decline in PrEP compliance in a prospective longitudinal cohort study.	Adolescent girls and young women (n=22)	Qualitative prospective cohort	Lack of family or partner support, traumatic events, and changes in the partnership. Decreased motivation, logistical barriers related to the health service, difficulty with the PrEP routine, forgetfulness, being busy, getting sick, changing residence, taking care of children, participating in cultural activities and difficulty in attending clinical appointments.	IV
Willie et al., 2021(³²32 Willie TC, Monger M, Nunn A, Kershaw T, Stockman JK, Mayer KH, et al. “PrEP’s just to secure you like insurance”: a qualitative study on HIV pre-exposure prophylaxis (PrEP) adherence and retention among black cisgender women in Mississippi. BMC Infect Dis. 2021;21:1102. https://doi.org/10.1186/s12879-021-06786-1 https://doi.org/10.1186/s12879-021-06786... )/ USA	Understand the multilevel factors that influence PrEP persistence.	Black cisgender women (n=8)	Qualitative/ individual interviews	Accessibility and costs of PrEP services, medication side effects (upset stomach, constipation, tachycardia and morning sickness).	V

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[1] Corresponding author: Renata Karina Reis, E-mail: rkreis@eerp.usp.brr