Current HIV/AIDS Reports

, Volume 13, Issue 2, pp 116–124 | Cite as

Successful Implementation of HIV Preexposure Prophylaxis: Lessons Learned From Three Clinical Settings

  • Julia L. Marcus
  • Jonathan E. Volk
  • Jess Pinder
  • Albert Y. Liu
  • Oliver Bacon
  • C. Bradley Hare
  • Stephanie E. CohenEmail author
The Science of Prevention (JD Stekler and J Baeten, Section Editors)
Part of the following topical collections:
  1. Topical Collection on The Science of Prevention


The past 3 years have marked a transition from research establishing the safety and efficacy of HIV preexposure prophylaxis (PrEP) to questions about how to optimize its implementation. Until recently, PrEP was primarily offered as part of randomized controlled trials or open-label studies. These studies highlighted the key components of PrEP delivery, including regular testing for HIV and other sexually transmitted infections (STIs), adherence and risk-reduction support, and monitoring for renal toxicity. PrEP is now increasingly provided in routine clinical settings. This review summarizes models for PrEP implementation from screening through initiation and follow-up, focusing on the strengths and weaknesses of three delivery systems: a health maintenance organization, an STI clinic, and a primary care practice. These early implementation experiences demonstrate that PrEP can be successfully delivered across a variety of settings and highlight strategies to streamline PrEP delivery in clinical practice.


Preexposure prophylaxis (PrEP) PrEP delivery PrEP implementation Human immunodeficiency virus (HIV) Implementation Sexually transmitted infections Delivery of health care Science of prevention Review 



This work was supported by a Kaiser Permanente Northern California Community Benefit research grant to Dr. Julia L. Marcus.

Compliance with Ethical Standards

Conflict of Interest

Julia L. Marcus reports grants from Merck.

Albert Y. Liu reports non-financial support from Gilead and personal fees from IAS-USA.

Stephanie E. Cohen reports non-financial support from Gilead.

Jonathan E. Volk, Jess Pinder, C. Bradley Hare, and Oliver Bacon declare they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367:399–410.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Thigpen MC, Kebaabetswe PM, Paxton LA, Smith DK, Rose CE, Segolodi TM, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012;367:423–34.CrossRefPubMedGoogle Scholar
  3. 3.
    Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363:2587–99.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Choopanya K, Martin M, Suntharasamai P, Sangkum U, Mock PA, Leethochawalit M, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2013;381:2083–90.CrossRefPubMedGoogle Scholar
  5. 5.
    Preexposure Prophylaxis for the Prevention of HIV Infection in the United States - 2014: A Clinical Practice Guideline. 2014. Available at: Accessed December 30, 2014.
  6. 6.•
    Grant RM, Anderson PL, McMahan V, Liu A, Amico KR, Mehrotra M, et al. Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study. Lancet. 2014;14:820–9. Uptake of PrEP was high in this open-label extension of randomized PrEP trials, particularly among individuals reporting condomless receptive anal intercourse. PrEP efficacy was highly correlated with drug concentrations in dried blood spots, and there were no HIV seroconversions in participants who had drug levels consistent with having taken four or more doses of TDF/FTC per week.CrossRefPubMedGoogle Scholar
  7. 7.•
    Cohen SE, Vittinghoff E, Bacon O, Doblecki-Lewis S, Postle BS, Feaster DJ, et al. High interest in preexposure prophylaxis among men who have sex with men at risk for HIV infection: baseline data from the US PrEP Demonstration Project. J Acquir Immune Defic Syndr. 2015;68:439–48. In this report of baseline data from an open-label demonstration project in STI clinics and a community health center in three US cities (The US Demonstration Project), uptake of PrEP was high in a diverse population of MSM at risk for HIV infection and did not vary by race/ethnicity, age, or education level.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hosek S, Rudy B, Landovitz R, Kapogiannis B, Siberry G, Liu N, et al. An HIV pre-exposure prophylaxis (PrEP) demonstration project and safety study for young men who have sex with men in the United States (ATN 110). In: 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Vancouver; 2015.Google Scholar
  9. 9.
    Flash C, Landovitz R, Giler RM, Ng L, Magnuson D, Wooley SB, et al. Two years of Truvada for pre-exposure prophylaxis utilization in the US. J Int AIDS Soc. 2014;17:19730.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Grant RM, Liu A, Hecht J, Buchbinder SP, Weber S, Crouch P, et al. Scale-up of preexposure prophylaxis in San Francisco to impact HIV incidence. In: 22nd Conference on Retroviruses and Opportunistic Infections. Seattle; 2015.Google Scholar
  11. 11.
    Mayer K, Krakower D, Levine K, Grasso C, Gelman M. Significant increases in HIV pre-exposure prophylaxis (PrEP) uptake in Boston, a Boston Community Health Center in 2014: who are the recent users? In: 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Vancouver; 2015.Google Scholar
  12. 12.
    Hood J, Buskin S, Barash E, Katz D, Dombrowski J, Golden M. Awareness and utilization of HIV prevention innovations among men who have sex with men in Seattle. In: 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Vancouver; 2015.Google Scholar
  13. 13.•
    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):1–11. In this report from the US Demonstration Project, adherence, as measured in dried blood spots, was higher than that observed in clinical trials of PrEP and was correlated with higher self-reported risk behaviors. HIV incidence was extremely low, despite a high incidence of STIs.Google Scholar
  14. 14.
    Koenig LJ, Lyles C, Smith DK. Adherence to antiretroviral medications for HIV pre-exposure prophylaxis: lessons learned from trials and treatment studies. Am J Prev Med. 2013;44:S91–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Martin M, Vanichseni S, Suntharasamai P, Sangkum U, Mock PA, Leethochawalit M, et al. The impact of adherence to preexposure prophylaxis on the risk of HIV infection among people who inject drugs. AIDS. 2015;29:819–24.CrossRefPubMedGoogle Scholar
  16. 16.
    Anderson PL, Glidden DV, Liu A, Buchbinder S, Lama JR, Guanira JV, et al. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med. 2012;4:151ra125.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Amico KR, Marcus JL, McMahan V, Liu A, Koester KA, Goicochea P, et al. Study product adherence measurement in the iPrEx placebo-controlled trial: concordance with drug detection. J Acquir Immune Defic Syndr. 2014;66:530–7.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Agot K, Taylor D, Corneli AL, Wang M, Ambia J, Kashuba AD, et al. Accuracy of self-report and pill-count measures of adherence in the FEM-PrEP clinical trial: implications for future HIV-prevention trials. AIDS Behav. 2015;19:743–51.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Mayer KH, Safren SA, Haberer J, Elsesser S, Clarke W, Hendrix CW, et al. Project PrEPARE: high levels of medication adherence with continued condomless sex in U.S. men who have sex with men in an oral PrEP adherence trial. AIDS Res Hum Retrovir. 2014;30:A23–4.CrossRefGoogle Scholar
  20. 20.
    Liu A, Stojanovski K, Lester RT, Amico KR, McMahan V, Goicochea P, et al. Developing and implementing a mobile health (mHealth) adherence support system for HIV-uninfected men who have sex with men (MSM) taking pre-exposure prophylaxis (PrEP): the iText Study. In: 8th International Conference on HIV Treatment and Prevention. Miami; 2014.Google Scholar
  21. 21.
    HPTN 073. Pre-exposure prophylaxis (PrEP) initiation and adherence among black men who have sex with men (BMSM) in three U.S. cities. Available at: Accessed September 3, 2015.
  22. 22.
    Lehman DA, Baeten JM, McCoy CO, Weis JF, Peterson D, Mbara G, et al. Risk of drug resistance among persons acquiring HIV within a randomized clinical trial of single- or dual-agent preexposure prophylaxis. J Infect Dis. 2015;211:1211–8.PubMedGoogle Scholar
  23. 23.
    Grant RM, Liegler T, Defechereux P, Kashuba AD, Taylor D, Abdel-Mohsen M, et al. Drug resistance and plasma viral RNA level after ineffective use of oral pre-exposure prophylaxis in women. AIDS. 2015;29:331–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Liegler T, Abdel-Mohsen M, Bentley LG, Atchison R, Schmidt T, Javier J, et al. HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. J Infect Dis. 2014;210:1217–27.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Mulligan K, Glidden DV, Anderson PL, Liu A, McMahan V, Gonzales P, et al. Effects of emtricitabine/tenofovir on bone mineral density in HIV-negative persons in a randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2015;61(4):572–80.Google Scholar
  26. 26.
    Liu AY, Vittinghoff E, Sellmeyer DE, Irvin R, Mulligan K, Mayer K, et al. Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco. PLoS ONE. 2011;6, e23688.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Mugwanya KK, Wyatt C, Celum C, Donnell D, Mugo NR, Tappero J, et al. Changes in glomerular kidney function among HIV-1-uninfected men and women receiving emtricitabine-tenofovir disoproxil fumarate preexposure prophylaxis: a randomized clinical trial. JAMA Int Med. 2015;175:246–54.CrossRefGoogle Scholar
  28. 28.
    Solomon MM, Lama JR, Glidden DV, Mulligan K, McMahan V, Liu AY, et al. Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis. AIDS. 2014;28(6):851–9.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Marcus JL, Glidden DV, Mayer KH, Liu AY, Buchbinder SP, Amico KR, et al. No evidence of sexual risk compensation in the iPrEx trial of daily oral HIV preexposure prophylaxis. PLoS ONE. 2013;8, e81997.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Mugwanya KK, Donnell D, Celum C, Thomas KK, Ndase P, Mugo N, et al. Sexual behaviour of heterosexual men and women receiving antiretroviral pre-exposure prophylaxis for HIV prevention: a longitudinal analysis. Lancet Infect Dis. 2013;13:1021–8.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Liu AY, Vittinghoff E, Chillag K, Mayer K, Thompson M, Grohskopf L, et al. Sexual risk behavior among HIV-uninfected men who have sex with men (MSM) participating in a tenofovir pre-exposure prophylaxis (PrEP) randomized trial in the United States. J Acquir Immune Defic Syndr. 2013;64(1):87-94.Google Scholar
  32. 32.
    Elsesser S, Biello K, Taylor S, Tomassilli J, Safren SA, Mayer K. Absence of sexual behavioral disinhibition in a PrEP adherence trial: considerations for medical providers who prescribe PrEP for men who have sex with men (MSM). In: 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Vancouver; 2015.Google Scholar
  33. 33.
    Milam J, Jain S, Moore D, Daar E, Dube M, Young J, et al. Risk compensation among men who have sex with men (MSM) in Southern California following the initiation of pre-exposure prophylaxis (PrEP). In: 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Vancouver; 2015.Google Scholar
  34. 34.
    Cassell MM, Halperin DT, Shelton JD, Stanton D. Risk compensation: the Achilles’ heel of innovations in HIV prevention? BMJ. 2006;332:605–7.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.••
    McCormack S, Dunn DT, Desai M, Dolling DI, Gafos M, Gilson R, et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet. 2016;387(10013):53-60. In this pragmatic open-label trial in the UK, participants at 13 sexual health clinics were randomized to receive immediate or deferred PrEP. HIV incidence was high in the deferred arm, with an 86 % risk reduction in the immediate arm. There was no evidence of an increase in STI incidence.Google Scholar
  36. 36.•
    Volk JE, Marcus JL, Phengrasamy T, Blechinger D, Nguyen DP, Follansbee S, et al. No new HIV infections with increasing use of HIV preexposure prophylaxis in a clinical practice setting. Clin Infect Dis. 2015;61(10):1601–3. This real-world evaluation of PrEP in a large clinical practice setting found No new HIV infections in a growing population of PrEP users, despite high STI incidence and a reported decrease in condom use in a subset of patients.Google Scholar
  37. 37.
    Volk JE, Marcus JL, Phengrasamy T, Hare CB. Incident hepatitis C virus infections among users of HIV preexposure prophylaxis in a clinical practice setting. Clin Infect Dis. 2015;60(11):1728–9.Google Scholar
  38. 38.
    California PrEP Provider Directory. HIVE, San Francisco General Hospital. Available at: Accessed July 14, 2015.
  39. 39.
    PrEP local medical services. Project Inform, San Francisco, CA. Available at: Accessed July 14, 2015.
  40. 40.
    van der Helm JJ, Hoebe CJ, van Rooijen MS, Brouwers EE, Fennema HS, Thiesbrummel HF, et al. High performance and acceptability of self-collected rectal swabs for diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae in men who have sex with men and women. Sex Transm Dis. 2009;36:493–7.CrossRefPubMedGoogle Scholar
  41. 41.
    Freeman AH, Bernstein KT, Kohn RP, Philip S, Rauch LM, Klausner JD. Evaluation of self-collected versus clinician-collected swabs for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae pharyngeal infection among men who have sex with men. Sex Transm Dis. 2011;38:1036–9.CrossRefPubMedGoogle Scholar
  42. 42.
    Gilead Sciences, Inc. Truvada for PrEP Medication Assistance Program. Available at: Accessed July 9, 2015.
  43. 43.
    Klein D, Hurley LB, Merrill D, Quesenberry Jr CP. Review of medical encounters in the 5 years before a diagnosis of HIV-1 infection: implications for early detection. J Acquir Immune Defic Syndr. 2003;32:143–52.CrossRefPubMedGoogle Scholar
  44. 44.
    Nurutdinova D, Rao S, Shacham E, Reno H, Overton ET. STD/HIV risk among adults in the primary care setting: are we adequately addressing our patients’ needs? Sex Transm Dis. 2011;38:30–2.CrossRefPubMedGoogle Scholar
  45. 45.
    Montano DE, Phillips WR, Kasprzyk D, Greek A. STD/HIV prevention practices among primary care clinicians: risk assessment, prevention counseling, and testing. Sex Transm Dis. 2008;35:154–66.CrossRefPubMedGoogle Scholar
  46. 46.
    Baeten JM, Haberer JE, Liu AY, Sista N. Preexposure prophylaxis for HIV prevention: where have we been and where are we going? J Acquir Immune Defic Syndr. 2013;63 Suppl 2:S122–9.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Liu A, Cohen S, Follansbee S, Cohan D, Weber S, Sachdev D, et al. Early experiences implementing pre-exposure prophylaxis (PrEP) for HIV prevention in San Francisco. PLoS Med. 2014;11, e1001613.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    San Francisco Department of Public Health. San Francisco Sexually Transmitted Disease Annual Summary, 2013. San Francisco Department of Public Health, San Francisco, California. December 2014. Available at: Accessed July 27, 2015.
  49. 49.
    Patel P, Klausner JD, Bacon OM, Liska S, Taylor M, Gonzalez A, et al. Detection of acute HIV infections in high-risk patients in California. J Acquir Immune Defic Syndr. 2006;42:75–9.CrossRefPubMedGoogle Scholar
  50. 50.
    Landovitz RJ, Combs KB, Currier JS. Availability of HIV postexposure prophylaxis services in Los Angeles County. Clin Infect Dis. 2009;48:1624–7.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Pre-Exposure Prophylaxis Drug Assistance Program (PrEP DAP). Washington State Department of Health. Available at: Accessed August 3, 2015.
  52. 52.
    Pre-Exposure Prophylaxis Assistance Program (PrEP-AP). New York State Department of Health. Available at: Accessed August 3, 2015.

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Julia L. Marcus
    • 1
  • Jonathan E. Volk
    • 2
  • Jess Pinder
    • 3
  • Albert Y. Liu
    • 4
  • Oliver Bacon
    • 4
  • C. Bradley Hare
    • 2
  • Stephanie E. Cohen
    • 4
    Email author
  1. 1.Division of ResearchKaiser Permanente Northern CaliforniaOaklandUSA
  2. 2.Kaiser Permanente Northern California, San Francisco Medical CenterSan FranciscoUSA
  3. 3.One Medical GroupSan FranciscoUSA
  4. 4.San Francisco Department of Public HealthUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations