Skip to main content


Log in

Improving Delivery and Use of HIV Pre-Exposure Prophylaxis in the US: A Systematic Review of Implementation Strategies and Adjunctive Interventions

  • Original Paper
  • Published:
AIDS and Behavior Aims and scope Submit manuscript


Implementation of pre-exposure prophylaxis (PrEP) to prevent HIV transmission is suboptimal in the United States. To date, the literature has focused on identifying determinants of PrEP use, with a lesser focus on developing and testing change methods to improve PrEP implementation. Moreover, the change methods available for improving the uptake and sustained use of PrEP have not been systematically categorized. To summarize the state of the literature, we conducted a systematic review of the implementation strategies used to improve PrEP implementation among delivery systems and providers, as well as the adjunctive interventions used to improve the uptake and persistent adherence to PrEP among patients. Between November 2020 and January 2021, we searched Ovid MEDLINE, PsycINFO, and Web of Science for peer reviewed articles. We identified 44 change methods (18 implementation strategies and 26 adjunctive interventions) across a variety of clinical and community-based service settings. We coded implementation strategies and adjunctive interventions in accordance with established taxonomies and reporting guidelines. Most studies focused on improving patient adherence to PrEP and most conducted pilot trials. Just over one-third of included studies demonstrated a positive effect on outcomes. In order to end the human immunodeficiency virus (HIV) epidemic in the U.S., future, large scale HIV prevention research is needed that develops and evaluates implementation strategies and adjunctive interventions for target populations disproportionately affected by HIV.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Data Availability

We included supplemental files of our codebook, which includes operational definitions of codes. The systematic review dashboard, which a portion of our studies were drawn from is freely available at Additional data is available from the authors upon request.


  1. Centers for Disease Control and Prevention. US Public Health Service: Preexposure prophylaxis for the prevention of HIV infection in the United States—2021 Update: a clinical practice guideline. 2021.

  2. U.S. Department of Health and Human Services. HIV National Strategic Plan for the United States: A Roadmap to End the Epidemic 2021–2025. Washington, D.C.2021.

  3. Bonacci RA, Smith DK, Ojikutu BO. Toward Greater Pre-exposure Prophylaxis Equity: Increasing Provision and Uptake for Black and Hispanic/Latino Individuals in the U.S. Am J Prev Med. 2021;61(5 Suppl 1):S60-s72.

  4. Centers for Disease Control and Prevention. PrEP for HIV Prevention in the U.S. 2021 [ Accessed.

  5. Pleuhs B, Quinn KG, Walsh JL, Petroll AE, John SA. Health care provider barriers to HIV pre-exposure prophylaxis in the United States: a systematic review. AIDS Patient Care STDs. 2020;34(3):111–23.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Haberer JE, Baeten JM, Campbell J, Wangisi J, Katabira E, Ronald A et al. Adherence to antiretroviral prophylaxis for HIV prevention: a substudy cohort within a clinical trial of serodiscordant couples in East Africa. PLoS Med. 2013;10(9):e1001511.

  7. Haberer JE, Bangsberg DR, Baeten JM, Curran K, Koechlin F, Amico KR et al. Defining success with HIV pre-exposure prophylaxis: a prevention-effective adherence paradigm. Aids. 2015;29(11):1277-85.

  8. Landovitz RJ, Beymer M, Kofron R, Amico KR, Psaros C, Bushman L et al. Plasma Tenofovir Levels to Support Adherence to TDF/FTC Preexposure Prophylaxis for HIV Prevention in MSM in Los Angeles, California. J Acquir Immune Defic Syndr. 2017;76(5):501–11.

  9. Zamantakis A, Li DH, Benbow N, Smith JD, Mustanski B. Determinants of Pre-exposure Prophylaxis (PrEP) Implementation in Transgender Populations: A Qualitative Scoping Review. AIDS Behav. 2023;27(5):1600-18.

  10. Hojilla JC, Vlahov D, Crouch PC, Dawson-Rose C, Freeborn K, Carrico A. HIV Pre-exposure Prophylaxis (PrEP) Uptake and Retention Among Men Who Have Sex with Men in a Community-Based Sexual Health Clinic. AIDS Behav. 2018;22(4):1096-9.

  11. Morgan E, Ryan DT, Newcomb ME, Mustanski B. High Rate of Discontinuation May Diminish PrEP Coverage Among Young Men Who Have Sex with Men. AIDS Behav. 2018;22(11):3645-8.

  12. Li DH, Benbow N, Keiser B, Mongrella M, Ortiz K, Villamar J et al. Determinants of Implementation for HIV Pre-exposure Prophylaxis Based on an Updated Consolidated Framework for Implementation Research: A Systematic Review. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2022;90(S1):S235-S46.

  13. Wensing M, Oxman A, Baker R, Godycki-Cwirko M, Flottorp S, Szecsenyi J et al. Tailored implementation for chronic diseases (TICD): A project protocol. Implementation Science. 2011;6(1):103.

  14. Damschroder LJ, Aron DC, Keith RE, Kirsh SR, Alexander JA, Lowery JC. Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science. Implement Sci. 2009;4:50.

  15. Damschroder LJ, Reardon CM, Widerquist MAO, Lowery J. The updated Consolidated Framework for Implementation Research based on user feedback. Implementation Science. 2022;17(1):75.

  16. Proctor EK, Powell BJ, McMillen JC. Implementation strategies: recommendations for specifying and reporting. Implementation Science. 2013;8(1):139.

  17. Rabin B, Viglione C, Brownson R, Brownson R, Colditz G, Proctor E., editor: Oxford University Press; 2023.

  18. Proctor E, Silmere H, Raghavan R, Hovmand P, Aarons G, Bunger A et al. Outcomes for implementation research: conceptual distinctions, measurement challenges, and research agenda. Adm Policy Ment Health. 2011;38(2):65–76.

  19. Damschroder LJ, Reardon CM, Opra Widerquist MA, Lowery J. Conceptualizing outcomes for use with the Consolidated Framework for Implementation Research (CFIR): the CFIR Outcomes Addendum. Implementation Science. 2022;17(1):7.

  20. Nunn AS, Brinkley-Rubinstein L, Oldenburg CE, Mayer KH, Mimiaga M, Patel R et al. Defining the HIV pre-exposure prophylaxis care continuum. Aids. 2017;31(5):731-4.

  21. Smith JD, Li DH, Merle JL, Keiser B, Mustanski B, Benbow ND. Adjunctive Interventions: Change Methods Directed at Recipients That Support Uptake and Use of Health Innovations. Implementation Science. 2024;19(1).

  22. Sullivan PS, Mena L, Elopre L, Siegler AJ. Implementation Strategies to Increase PrEP Uptake in the South. Curr HIV/AIDS Rep. 2019;16(4):259–69.

  23. Celum CL, Delany-Moretlwe S, McConnell M, van Rooyen H, Bekker LG, Kurth A et al. Rethinking HIV prevention to prepare for oral PrEP implementation for young African women. J Int AIDS Soc. 2015;18(4 Suppl 3).

  24. Mustanski B, Saber R, Macapagal K, Matson M, Laber E, Rodrgiuez-Diaz C et al. Effectiveness of the SMART Sex Ed program among 13–18 year old English and Spanish speaking adolescent men who have sex with men. AIDS Behav. 2023;27(2):733–44.

  25. Shangani S, Bhaskar N, Richmond N, van den Operario D. A systematic review of early adoption of implementation science for HIV prevention or treatment in the United States. AIDS. 2021;35(2):177–91.

  26. Marcus JL, Buisker T, Horvath T, Amico KR, Fuchs JD, Buchbinder SP et al. Helping our patients take HIV pre-exposure prophylaxis (PrEP): a systematic review of adherence interventions. HIV Med. 2014;15(7):385–95.

  27. Sidebottom D, Ekström AM, Strömdahl S. A systematic review of adherence to oral pre-exposure prophylaxis for HIV – how can we improve uptake and adherence? BMC Infectious Diseases. 2018;18(1):581.

  28. Mirzazadeh A, Eshun-Wilson I, Thompson RR, Bonyani A, Kahn JG, Baral SD et al. Interventions to reengage people living with HIV who are lost to follow-up from HIV treatment programs: A systematic review and meta-analysis. PLoS Med. 2022;19(3):e1003940.

  29. Covidence systematic review software. Veritas Health Innov Melbourne Australia. 2022; Available at:

  30. Merle JL, Li D, Keiser B, Zamantakis A, Queiroz A, Gallo CG et al. Categorising implementation determinants and strategies within the US HIV implementation literature: a systematic review protocol. BMJ Open. 2023;13(3):e070216.

  31. Smith JD, Li DH, Rafferty MR. The Implementation Research Logic Model: a method for planning, executing, reporting, and synthesizing implementation projects. Implementation Science. 2020;15(1).

  32. Powell BJ, Waltz TJ, Chinman MJ, Damschroder LJ, Smith JL, Matthieu MM et al. A refined compilation of implementation strategies: results from the Expert Recommendations for Implementing Change (ERIC) project. Implement Sci. 2015;10:21.

  33. Waltz TJ, Powell BJ, Matthieu MM, Damschroder LJ, Chinman MJ, Smith JL et al. Use of concept mapping to characterize relationships among implementation strategies and assess their feasibility and importance: results from the Expert Recommendations for Implementing Change (ERIC) study. Implement Sci. 2015;10:109.

  34. Hwang S, Birken SA, Melvin CL, Rohweder CL, Smith JD. Designs and methods for implementation research: advancing the mission of the CTSA program. J Clin Translational Sci. 2020;4(3):159–67.

    Article  Google Scholar 

  35. Baumann AA, Cabassa LJ. Reframing implementation science to address inequities in healthcare delivery. BMC Health Services Research. 2020;20(1):190.

  36. Brownson RC, Kumanyika SK, Kreuter MW, Haire-Joshu D. Implementation science should give higher priority to health equity. Implementation Science. 2021;16(1):28.

  37. McNulty M, Smith JD, Villamar J, Burnett-Zeigler I, Vermeer W, Benbow N et al. Implementation Research Methodologies for Achieving Scientific Equity and Health Equity. Ethn Dis. 2019;29(Suppl 1):83–92.

  38. Centers for Disease Control and Prevention. HIV Prevention In the United States. Mobilizing the End of the Epidemic 2022 [,Black%20women%2C%20and%20transgender%20women. Accessed 9/11/2023.

  39. Blase K, Fixsen D. Core intervention components: identifying and operationalizing what makes Programs Work. ASPE Research brief. US Department of Health and Human Services; 2013.

  40. Atkins L, Francis J, Islam R, O’Connor D, Patey A, Ivers N et al. A guide to using the Theoretical Domains Framework of behaviour change to investigate implementation problems. Implementation Science. 2017;12(1):77.

  41. Cane J, O’Connor D, Michie S. Validation of the theoretical domains framework for use in behaviour change and implementation research. Implementation Science. 2012;7(1):37.

  42. Michie S, van Stralen MM, West R. The behaviour change wheel: A new method for characterising and designing behaviour change interventions. Implementation Science. 2011;6(1):42.

  43. Landes SJ, McBain SA, Curran GM. An introduction to effectiveness-implementation hybrid designs. Psychiatry Res. 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Gregg E, Linn C, Nace E, Gelberg L, Cowan B, Fulcher JA. Implementation of HIV Preexposure Prophylaxis in a Homeless Primary Care Setting at the Veterans Affairs. J Prim Care Community Health. 2020;11:2150132720908370.

  45. Roth AM, Tran NK, Felsher M, Gadegbeku AB, Piecara B, Fox R et al. Integrating HIV Preexposure Prophylaxis With Community-Based Syringe Services for Women Who Inject Drugs: Results From the Project SHE Demonstration Study. J Acquir Immune Defic Syndr. 2021;86(3):e61-e70.

  46. Leeman J, Birken SA, Powell BJ, Rohweder C, Shea CM. Beyond implementation strategies: classifying the full range of strategies used in implementation science and practice. Implementation Science. 2017;12:1–9.

  47. Brownson RC, Eyler AA, Harris JK, Moore JB, Tabak RG. Getting the Word Out: New Approaches for Disseminating Public Health Science. J Public Health Manag Pract. 2018;24(2):102 – 11.

  48. Teitelman AM, Tieu HV, Chittamuru D, Shaw PA, Nandi V, Davis A et al. A Randomized Controlled Pilot Study of Just4Us, a Counseling and Navigation Intervention to Promote Oral HIV Prophylaxis Uptake Among PrEP-Eligible Cisgender Women. AIDS Behav. 2023;27(9):2944-58.

  49. Hosek SG, Green KR, Siberry G, Lally M, Balthazar C, Serrano PA et al. Integrating Behavioral HIV Interventions into Biomedical Prevention Trials with Youth: Lessons from Chicago’s Project PrEPare. J HIV AIDS Soc Serv. 2013;12(3–4).

  50. Teitelman AM, Koblin BA, Brawner BM, Davis A, Darlington C, Lipsky RK et al. Just4Us: Development of a Counselor-Navigator and Text Message Intervention to Promote PrEP Uptake Among Cisgender Women at Elevated Risk for HIV. J Assoc Nurses AIDS Care. 2021;32(2):188–204.

  51. Smith JD, Li DH, Hirschhorn LR, Gallo C, McNulty M, Phillips G et al. Landscape of HIV Implementation Research Funded by the National Institutes of Health: A Mapping Review of Project Abstracts. AIDS and Behavior. 2020;24(6):1903-11.

  52. Kanny D, Jeffries IVWL, Chapin-Bardales J, Denning P, Cha S, Finlayson T, et al. Racial/ethnic disparities in HIV preexposure prophylaxis among men who have sex with men—23 urban areas, 2017. Morb Mortal Wkly Rep. 2019;68(37):801.

    Article  Google Scholar 

  53. Bunting SR, Saqueton R, Batteson TJ. A Guide for Designing Student-Led, Interprofessional Community Education Initiatives About HIV Risk and Pre-Exposure Prophylaxis. MedEdPORTAL. 2019;15:10818.

  54. Burns PA, Omondi AA, Monger M, Ward L, Washington R, Sims Gomillia CE et al. Meet Me Where I Am: An Evaluation of an HIV Patient Navigation Intervention to Increase Uptake of PrEP Among Black Men Who Have Sex with Men in the Deep South. J Racial Ethn Health Disparities. 2022;9(1):103–16.

  55. Chen A, Dowdy DW. Clinical effectiveness and cost-effectiveness of HIV pre-exposure prophylaxis in men who have sex with men: risk calculators for real-world decision-making. PLoS One. 2014;9(10):e108742.

  56. Saberi P, Berrean B, Thomas S, Gandhi M, Scott H. A Simple Pre-Exposure Prophylaxis (PrEP) Optimization Intervention for Health Care Providers Prescribing PrEP: Pilot Study. JMIR Form Res. 2018;2(1).

  57. Brant AR, Dhillon P, Hull S, Coleman M, Ye PP, Lotke PS et al. Integrating HIV Pre-Exposure Prophylaxis into Family Planning Care: A RE-AIM Framework Evaluation. AIDS Patient Care STDS. 2020;34(6):259–66.

  58. Horack CL, Newton SL, Vos M, Wolfe BA, Whitaker A. Pre-Exposure Prophylaxis in a Reproductive Health Setting: A Quality Improvement Project. Health Promot Pract. 2020;21(5):687-9.

  59. Havens JP, Scarsi KK, Sayles H, Klepser DG, Swindells S, Bares SH. Acceptability and feasibility of a pharmacist-led HIV pre-exposure prophylaxis (PrEP) program in the Midwestern United States. Open Forum Infect Dis. 2019;6(10).

  60. Khosropour CM, Backus KV, Means AR, Beauchamps L, Johnson K, Golden MR et al. A Pharmacist-Led, Same-Day, HIV Pre-Exposure Prophylaxis Initiation Program to Increase PrEP Uptake and Decrease Time to PrEP Initiation. AIDS Patient Care STDS. 2020;34(1):1–6.

  61. Buchbinder SP, Havlir DV. Getting to Zero San Francisco: A Collective Impact Approach. J Acquir Immune Defic Syndr. 2019;82 Suppl 3(Suppl 3):S176-s82.

  62. Fuchs JD, Stojanovski K, Vittinghoff E, McMahan VM, Hosek SG, Amico KR et al. A Mobile Health Strategy to Support Adherence to Antiretroviral Preexposure Prophylaxis. AIDS Patient Care STDS. 2018;32(3):104–11.

  63. Hoenigl M, Hassan A, Moore DJ, Anderson PL, Corado K, Dubé MP et al. Predictors of Long-Term HIV Pre-exposure Prophylaxis Adherence After Study Participation in Men Who Have Sex With Men. J Acquir Immune Defic Syndr. 2019;81(2):166–74.

  64. Liu AY, Vittinghoff E, von Felten P, Rivet Amico K, Anderson PL, Lester R et al. Randomized Controlled Trial of a Mobile Health Intervention to Promote Retention and Adherence to Preexposure Prophylaxis Among Young People at Risk for Human Immunodeficiency Virus: The EPIC Study. Clin Infect Dis. 2019;68(12):2010-7.

  65. Desrosiers A, Levy M, Dright A, Zumer M, Jallah N, Kuo I et al. A Randomized Controlled Pilot Study of a Culturally-Tailored Counseling Intervention to Increase Uptake of HIV Pre-exposure Prophylaxis Among Young Black Men Who Have Sex with Men in Washington, DC. AIDS Behav. 2019;23(1):105–15.

  66. Liu AY, Cohen SE, Vittinghoff E, Anderson PL, Doblecki-Lewis S, Bacon O et al. Preexposure Prophylaxis for HIV Infection Integrated With Municipal- and Community-Based Sexual Health Services. JAMA Intern Med. 2016;176(1):75–84.

  67. Mitchell JT, LeGrand S, Hightow-Weidman LB, McKellar MS, Kashuba AD, Cottrell M et al. Smartphone-Based Contingency Management Intervention to Improve Pre-Exposure Prophylaxis Adherence: Pilot Trial. JMIR Mhealth Uhealth. 2018;6(9):e10456.

  68. Colson PW, Franks J, Wu Y, Winterhalter FS, Knox J, Ortega H et al. Adherence to Pre-exposure Prophylaxis in Black Men Who Have Sex with Men and Transgender Women in a Community Setting in Harlem, NY. AIDS Behav. 2020;24(12):3436-55.

  69. Klein CH, Kuhn T, Huxley D, Kennel J, Withers E, Lomonaco CG. Preliminary Findings of a Technology-Delivered Sexual Health Promotion Program for Black Men Who Have Sex With Men: Quasi-Experimental Outcome Study. JMIR Public Health Surveill. 2017;3(4):e78.

  70. Pinnock H, Barwick M, Carpenter CR, Eldridge S, Grandes G, Griffiths CJ et al. Standards for Reporting Implementation Studies (StaRI) Statement. Bmj. 2017;356:i6795.

  71. Merle JL, Thayer AJ, Larson MF, Pauling S, Cook CR, Rios JA, et al. Investigating strategies to increase general education teachers’ adherence to evidence-based social-emotional behavior practices: a meta-analysis of the single-case literature. J Sch Psychol. 2022;91:1–26.

    Article  PubMed  Google Scholar 

  72. Powell BJ, Fernandez ME, Williams NJ, Aarons GA, Beidas RS, Lewis CC et al. Enhancing the Impact of Implementation Strategies in Healthcare: A Research Agenda. Frontiers in Public Health. 2019;7.

  73. Michie S, Carey RN, Johnston M, Rothman AJ, de Bruin M, Kelly MP et al. From Theory-Inspired to Theory-Based Interventions: A Protocol for Developing and Testing a Methodology for Linking Behaviour Change Techniques to Theoretical Mechanisms of Action. Annals of Behavioral Medicine. 2017;52(6):501–12.

  74. Almirall D, Nahum-Shani I, Sherwood NE, Murphy SA. Introduction to SMART designs for the development of adaptive interventions: with application to weight loss research. Transl Behav Med. 2014;4(3):260–74.

  75. Dalton JE, Bolen SD, Mascha EJ. Publication Bias: The Elephant in the Review. Anesth Analg. 2016;123(4):812-3.

  76. Nilsen P, Bernhardsson S. Context matters in implementation science: a scoping review of determinant frameworks that describe contextual determinants for implementation outcomes. BMC Health Services Research. 2019;19(1):189.

  77. Huebner DM, Mustanski B. Navigating the Long Road Forward for Maximizing PrEP Impact Among Adolescent Men Who Have Sex with Men. Arch Sex Behav. 2020;49(1):211-6.

Download references


This work was supported by a supplement grant to the Third Coast Center for AIDS Research, an NIH-funded center (P30 AI117943; PI: D’Aquila; Supplement PIs: Mustanski & Benbow). J.D. Smith was supported by the CIRCL-Chicago Implementation Research Center (UG3 HL154297) and the Utah Clinical and Translational Science Institute (UM1 TR004409). James Merle was supported by a training grant from the National Library of Medicine (T15LM007124; PI: Eilbeck). JPZ and az’s time was supported by a training grant from the National Institute of Mental Health (T32MH130325; PI: Newcomb). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information

Authors and Affiliations



BM, DL, NB, and JDS conceived of the paper. DL and BK performed the literature search. JLM, DL, BK, JPZ, AQ, AZ, VM, and JV conducted the screening for inclusion and contributed to the coding. JLM performed the data analysis and synthesis. All authors drafted and/or critically revised the work.

Corresponding author

Correspondence to James L. Merle.

Ethics declarations

Compliance with Ethical Standards

This research involved searching previously published literature and did not involve human subjects.

Competing Interests

The authors have no relevant financial interests to disclose. Dr. Brian Mustanksi is an associate editor of the journal.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Merle, J.L., Benbow, N., Li, D.H. et al. Improving Delivery and Use of HIV Pre-Exposure Prophylaxis in the US: A Systematic Review of Implementation Strategies and Adjunctive Interventions. AIDS Behav (2024).

Download citation

  • Accepted:

  • Published:

  • DOI: