[Skip to Content]
[Skip to Content Landing]
HIV

HIV Preexposure ProphylaxisA Review

Educational Objective
To review the efficacy and safety of preexposure prophylaxis (PrEP) to prevent HIV transmission.
1 Credit CME
Abstract

Importance  About 40 000 Americans and 2 million people worldwide are newly infected with HIV each year. The combination antiretroviral regimen, tenofovir disoproxil fumarate (TDF)/emtricitabine, taken as a single pill once daily, has been shown to prevent HIV transmission but is used by fewer than 20% of people who could benefit in the United States.

Observations  PubMed was searched on February 15, 2018, using the search terms pre-exposure, prophylaxis, HIV, and PrEP to identify English-language articles published between 2010 and 2018. Four placebo-controlled randomized clinical trials have demonstrated that preexposure prophylaxis (PrEP) with daily dosing of TDF/emtricitabine significantly reduces HIV acquisition in men who have sex with men, high-risk heterosexuals, and injection drug users who share injection equipment. The efficacy of daily TDF/emtricitabine exceeds 90% but is highly correlated with degree of adherence. TDF/emtricitabine is safe and well-tolerated. Only 2% of people discontinue PrEP because of adverse effects. Sexually transmitted infections are common among those using PrEP. Resistance to TDF/emtricitabine when used for PrEP is rare (<0.1%) and usually occurs when PrEP is inadvertently prescribed to individuals with undiagnosed acute HIV infection who have false-negative findings on HIV antibody/antigen testing due to HIV infection acquired within 7 to 10 days of testing. Effective methods are needed to identify individuals at high risk for acquiring HIV, ensure their access to PrEP, and maximize medication adherence.

Conclusions and Relevance  TDF/emtricitabine is an effective and safe therapy for preventing HIV transmission. Increasing prescription of TDF/emtricitabine for patients at risk of acquiring HIV has the potential to reduce new HIV infections.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Article Information

Corresponding Author: James Riddell IV, MD, University of Michigan Medical Center, 1500 E Medical Center Dr, University Hospital South F4131, Ann Arbor, MI 48109-5378 (jriddell@umich.edu).

Accepted for Publication: February 19, 2018.

Author Contributions: Dr Riddell had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Amico, Mayer.

Acquisition, analysis, or interpretation of data: Riddell, Mayer.

Drafting of the manuscript: All authors.

Critical revision of the manuscript for important intellectual content: Mayer.

Supervision: Riddell.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Riddell reported receiving grant support from GlaxoSmithKline and ViiV Healthcare. Dr Amico reported receiving an educational grant through the University of Michigan from Gilead Sciences for material development for PrEP awareness and serving as an expert in an advisory meeting in May 2017 for Gilead Sciences. Dr Mayer reported receiving unrestricted research grants from Gilead Sciences and ViiV Healthcare.

References
1.
Hess  K, Johnson  A, Hu  X,  et al. HIV Surveillance Report: diagnoses of HIV infection in the United States and dependent areas, 2016. Centers for Disease Control and Prevention website. https://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-surveillance-report-2016-vol-28.pdf. 2017. Accessed February 19, 2018.
2.
World Health Statistics 2017: Monitoring Health for the SDGs. World Health Organization website. http://www.who.int/gho/publications/world_health_statistics/2017/en/. 2017. Accessed March 2, 2018.
3.
Johnson  A, Hess  K, Hu  S,  et al. HIV Surveillance Report Supplemental Report: monitoring selected national HIV prevention and care objectives by using HIV surveillance data—United States and 6 dependent areas, 2014. Centers for Disease Control and Prevention website. https://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-surveillance-supplemental-report-vol-21-4.pdf. 2016. Accessed February 19, 2018.
4.
Patel  P, Borkowf  CB, Brooks  JT, Lasry  A, Lansky  A, Mermin  J.  Estimating per-act HIV transmission risk: a systematic review.  AIDS. 2014;28(10):1509-1519.PubMedGoogle ScholarCrossref
5.
Rodger  AJ, Cambiano  V, Bruun  T,  et al; PARTNER Study Group.  Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy.  JAMA. 2016;316(2):171-181.PubMedGoogle ScholarCrossref
6.
Cohen  MS, Chen  YQ, McCauley  M,  et al; HPTN 052 Study Team.  Prevention of HIV-1 infection with early antiretroviral therapy.  N Engl J Med. 2011;365(6):493-505.PubMedGoogle ScholarCrossref
7.
Centers for Disease Control and Prevention (CDC). Trends in U.S. HIV diagnoses, 2005-2014. CDC website. https://www.cdc.gov/nchhstp/newsroom/docs/factsheets/hiv-data-trends-fact-sheet-508.pdf. 2016. Accessed February 19, 2018.
8.
García-Lerma  JG, Cong  ME, Mitchell  J,  et al.  Intermittent prophylaxis with oral Truvada protects macaques from rectal SHIV infection.  Sci Transl Med. 2010;2(14):14ra4.PubMedGoogle ScholarCrossref
9.
Cardo  DM, Culver  DH, Ciesielski  CA,  et al; Centers for Disease Control and Prevention Needlestick Surveillance Group.  A case-control study of HIV seroconversion in health care workers after percutaneous exposure.  N Engl J Med. 1997;337(21):1485-1490.PubMedGoogle ScholarCrossref
10.
Buchbinder  SP, Liu  A.  Pre-exposure prophylaxis and the promise of combination prevention approaches.  AIDS Behav. 2011;15(suppl 1):S72-S79.PubMedGoogle ScholarCrossref
11.
Grant  RM, Lama  JR, Anderson  PL,  et al; iPrEx Study Team.  Preexposure chemoprophylaxis for HIV prevention in men who have sex with men.  N Engl J Med. 2010;363(27):2587-2599.PubMedGoogle ScholarCrossref
12.
Baeten  JM, Donnell  D, Ndase  P,  et al; Partners PrEP Study Team.  Antiretroviral prophylaxis for HIV prevention in heterosexual men and women.  N Engl J Med. 2012;367(5):399-410.PubMedGoogle ScholarCrossref
13.
McCormack  S, Dunn  DT, Desai  M,  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.PubMedGoogle ScholarCrossref
14.
Anderson  PL, Glidden  DV, Liu  A,  et al; iPrEx Study Team.  Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men.  Sci Transl Med. 2012;4(151):151ra125.PubMedGoogle ScholarCrossref
15.
Adams  LM, Balderson  BH.  HIV providers’ likelihood to prescribe pre-exposure prophylaxis (PrEP) for HIV prevention differs by patient type: a short report.  AIDS Care. 2016;28(9):1154-1158.PubMedGoogle ScholarCrossref
16.
Thigpen  MC, Kebaabetswe  PM, Paxton  LA,  et al; TDF2 Study Group.  Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana.  N Engl J Med. 2012;367(5):423-434.PubMedGoogle ScholarCrossref
17.
Choopanya  K, Martin  M, Suntharasamai  P,  et al; Bangkok Tenofovir Study Group.  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(9883):2083-2090.PubMedGoogle ScholarCrossref
18.
Molina  JM, Capitant  C, Spire  B,  et al; ANRS IPERGAY Study Group.  On-demand preexposure prophylaxis in men at high risk for HIV-1 infection.  N Engl J Med. 2015;373(23):2237-2246.PubMedGoogle ScholarCrossref
19.
Marrazzo  JM, Ramjee  G, Richardson  BA,  et al; VOICE Study Team.  Tenofovir-based preexposure prophylaxis for HIV infection among African women.  N Engl J Med. 2015;372(6):509-518.PubMedGoogle ScholarCrossref
20.
Van Damme  L, Corneli  A, Ahmed  K,  et al; FEM-PrEP Study Group.  Preexposure prophylaxis for HIV infection among African women.  N Engl J Med. 2012;367(5):411-422.PubMedGoogle ScholarCrossref
21.
Mayer  KH, Ramjee  G.  The current status of the use of oral medication to prevent HIV transmission.  Curr Opin HIV AIDS. 2015;10(4):226-232.PubMedGoogle ScholarCrossref
22.
Anderson  PL, Liu  AY, Castillo-Mancilla  JR,  et al.  Intracellular tenofovir-diphosphate and emtricitabine-triphosphate in dried blood spots following directly observed therapy.  Antimicrob Agents Chemother. 2017;62(1):e01710-e1717. PubMedGoogle Scholar
23.
Marcus  JL, Hurley  LB, Hare  CB,  et al.  Preexposure prophylaxis for HIV prevention in a large integrated health care system: adherence, renal safety, and discontinuation.  J Acquir Immune Defic Syndr. 2016;73(5):540-546. PubMedGoogle ScholarCrossref
24.
Patterson  KB, Prince  HA, Kraft  E,  et al.  Penetration of tenofovir and emtricitabine in mucosal tissues: implications for prevention of HIV-1 transmission.  Sci Transl Med. 2011;3(112):112re4.PubMedGoogle ScholarCrossref
25.
Hanscom  B, Janes  HE, Guarino  PD,  et al.  Brief report: preventing HIV-1 infection in women using oral preexposure prophylaxis: a meta-analysis of current evidence.  J Acquir Immune Defic Syndr. 2016;73(5):606-608.PubMedGoogle ScholarCrossref
26.
Liu  AY, Cohen  SE, Vittinghoff  E,  et al.  Preexposure prophylaxis for HIV infection integrated with municipal- and community-based sexual health services.  JAMA Intern Med. 2016;176(1):75-84.PubMedGoogle ScholarCrossref
27.
Volk  JE, Marcus  JL, Phengrasamy  T,  et al.  No new HIV infections with increasing use of HIV preexposure prophylaxis in a clinical practice setting.  Clin Infect Dis. 2015;61(10):1601-1603.PubMedGoogle ScholarCrossref
28.
Hosek  SG, Rudy  B, Landovitz  R,  et al; Adolescent Trials Network (ATN) for HIVAIDS Interventions.  An HIV preexposure prophylaxis demonstration project and safety study for young MSM.  J Acquir Immune Defic Syndr. 2017;74(1):21-29.PubMedGoogle ScholarCrossref
29.
Hosek  SG, Landovitz  RJ, Kapogiannis  B,  et al.  Safety and feasibility of antiretroviral preexposure prophylaxis for adolescent men who have sex with men aged 15 to 17 years in the United States.  JAMA Pediatr. 2017;171(11):1063-1071.PubMedGoogle ScholarCrossref
30.
Baeten  JM, Heffron  R, Kidoguchi  L,  et al; Partners Demonstration Project Team.  Integrated delivery of antiretroviral treatment and pre-exposure prophylaxis to HIV-1-serodiscordant couples: a prospective implementation study in Kenya and Uganda.  PLoS Med. 2016;13(8):e1002099.PubMedGoogle ScholarCrossref
31.
Smith  DK, Van Handel  M, Wolitski  RJ,  et al.  Vital signs: estimated percentages and numbers of adults with indications for preexposure prophylaxis to prevent HIV acquisition—United States, 2015.  MMWR Morb Mortal Wkly Rep. 2015;64(46):1291-1295.PubMedGoogle ScholarCrossref
32.
Mayer  KH, Krakower  DS, Boswell  SL.  Antiretroviral preexposure prophylaxis: opportunities and challenges for primary care physicians.  JAMA. 2016;315(9):867-868.PubMedGoogle ScholarCrossref
33.
Mayer  KH, Chan  PA, Patel  R, Flash  CA, Krakower  DS.  Evolving models and ongoing challenges for HIV preexposure prophylaxis implementation in the United States.  J Acquir Immune Defic Syndr. 2018;77(2):119-127.PubMedGoogle Scholar
34.
Krakower  DS, Oldenburg  CE, Mitty  JA,  et al.  Knowledge, beliefs and practices regarding antiretroviral medications for HIV prevention: results from a survey of healthcare providers in New England.  PLoS One. 2015;10(7):e0132398.PubMedGoogle ScholarCrossref
35.
US Public Health Service. Preexposure prophylaxis for the prevention of HIV infection in the United States—2014: a clinical practice guideline. Centers for Disease Control and Prevention website. https://www.cdc.gov/hiv/pdf/prepguidelines2014.pdf. 2014. Accessed February 19, 2018.
36.
Solomon  MM, Schechter  M, Liu  AY,  et al; iPrEx Study Team.  The safety of tenofovir-emtricitabine for HIV pre-exposure prophylaxis (PrEP) in individuals with active hepatitis B.  J Acquir Immune Defic Syndr. 2016;71(3):281-286.PubMedGoogle ScholarCrossref
37.
Marcus  JL, Volk  JE, Pinder  J,  et al.  Successful implementation of HIV preexposure prophylaxis: lessons learned from three clinical settings.  Curr HIV/AIDS Rep. 2016;13(2):116-124. PubMedGoogle ScholarCrossref
38.
Medland  NA, Chow  EP, Walker  RG, Chen  M, Read  TR, Fairley  CK.  Incidence of renal Fanconi syndrome in patients taking antiretroviral therapy including tenofovir disoproxil fumarate.  Int J STD AIDS. 2018;29(3):227-236.PubMedGoogle ScholarCrossref
39.
Herlitz  LC, Mohan  S, Stokes  MB, Radhakrishnan  J, D’Agati  VD, Markowitz  GS.  Tenofovir nephrotoxicity: acute tubular necrosis with distinctive clinical, pathological, and mitochondrial abnormalities.  Kidney Int. 2010;78(11):1171-1177.PubMedGoogle ScholarCrossref
40.
Mugwanya  K, Baeten  J, Celum  C,  et al; Partners PrEP Study Team.  Low risk of proximal tubular dysfunction associated with emtricitabine-tenofovir disoproxil fumarate preexposure prophylaxis in men and women.  J Infect Dis. 2016;214(7):1050-1057.PubMedGoogle ScholarCrossref
41.
Kasonde  M, Niska  RW, Rose  C,  et al.  Bone mineral density changes among HIV-uninfected young adults in a randomised trial of pre-exposure prophylaxis with tenofovir-emtricitabine or placebo in Botswana.  PLoS One. 2014;9(3):e90111.PubMedGoogle ScholarCrossref
42.
Grigsby  IF, Pham  L, Mansky  LM, Gopalakrishnan  R, Carlson  AE, Mansky  KC.  Tenofovir treatment of primary osteoblasts alters gene expression profiles: implications for bone mineral density loss.  Biochem Biophys Res Commun. 2010;394(1):48-53.PubMedGoogle ScholarCrossref
43.
Murnane  PM, Heffron  R, Ronald  A,  et al; Partners PrEP Study Team.  Pre-exposure prophylaxis for HIV-1 prevention does not diminish the pregnancy prevention effectiveness of hormonal contraception.  AIDS. 2014;28(12):1825-1830.PubMedGoogle ScholarCrossref
44.
Matthews  LT, Baeten  JM, Celum  C, Bangsberg  DR.  Periconception pre-exposure prophylaxis to prevent HIV transmission: benefits, risks, and challenges to implementation.  AIDS. 2010;24(13):1975-1982.PubMedGoogle ScholarCrossref
45.
Mofenson  LM.  Tenofovir pre-exposure prophylaxis for pregnant and breastfeeding women at risk of HIV infection: the time is now.  PLoS Med. 2016;13(9):e1002133.PubMedGoogle ScholarCrossref
46.
Mayer  KH, Maloney  KM, Levine  K,  et al.  Sociodemographic and clinical factors associated with increasing bacterial sexually transmitted infection diagnoses in men who have sex with men accessing care at a Boston community health center (2005-2015).  Open Forum Infect Dis. 2017;4(4):ofx214. PubMedGoogle ScholarCrossref
47.
Hurt  CB, Eron  JJ  Jr, Cohen  MS.  Pre-exposure prophylaxis and antiretroviral resistance: HIV prevention at a cost?  Clin Infect Dis. 2011;53(12):1265-1270.PubMedGoogle ScholarCrossref
48.
Knox  DC, Anderson  PL, Harrigan  PR, Tan  DH.  Multidrug-resistant HIV-1 infection despite preexposure prohylaxis.  N Engl J Med. 2017;376(5):501-502. PubMedGoogle ScholarCrossref
49.
Markowitz  M, Grossman  H, Anderson  PL,  et al.  Newly acquired infection with multidrug-resistant HIV-1 in a patient adherent to preexposure prophylaxis.  J Acquir Immune Defic Syndr. 2017;76(4):e104-e106. PubMedGoogle ScholarCrossref
50.
Hoornenborg  E, Prins  M, Achterbergh  RCA,  et al; Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam Consortium (H-TEAM).  Acquisition of wild-type HIV-1 infection in a patient on pre-exposure prophylaxis with high intracellular concentrations of tenofovir diphosphate: a case report.  Lancet HIV. 2017;4(11):e522-e528. PubMedGoogle ScholarCrossref
51.
Branson  B, Owen  S, Wesolowski  L,  et al. Laboratory testing for the diagnosis of HIV infection: updated recommendations. Centers for Disease Control and Prevention website. https://stacks.cdc.gov/view/cdc/23447. 2014. Accessed February 19, 2018.
52.
Nel  A, van Niekerk  N, Kapiga  S,  et al; Ring Study Team.  Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women.  N Engl J Med. 2016;375(22):2133-2143.PubMedGoogle ScholarCrossref
53.
Markowitz  M, Frank  I, Grant  RM,  et al.  Safety and tolerability of long-acting cabotegravir injections in HIV-uninfected men (ECLAIR): a multicentre, double-blind, randomised, placebo-controlled, phase 2a trial.  Lancet HIV. 2017;4(8):e331-e340.PubMedGoogle ScholarCrossref
54.
Ledgerwood  JE, Coates  EE, Yamshchikov  G,  et al; VRC 602 Study Team.  Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults.  Clin Exp Immunol. 2015;182(3):289-301.PubMedGoogle ScholarCrossref
55.
AMP HIV Prevention Study website. http://www.ampstudy.org/. Accessed February 19, 2018.
56.
Hua  CK, Ackerman  ME.  Increasing the clinical potential and applications of anti-HIV antibodies.  Front Immunol. 2017;8:1655.PubMedGoogle ScholarCrossref
57.
Puri  A, Sivaraman  A, Zhang  W, Clark  MR, Banga  AK.  Expanding the domain of drug delivery for HIV prevention: exploration of the transdermal route.  Crit Rev Ther Drug Carrier Syst. 2017;34(6):551-587.PubMedGoogle ScholarCrossref
58.
Gunawardana  M, Remedios-Chan  M, Miller  CS,  et al.  Pharmacokinetics of long-acting tenofovir alafenamide (GS-7340) subdermal implant for HIV prophylaxis.  Antimicrob Agents Chemother. 2015;59(7):3913-3919.PubMedGoogle ScholarCrossref
59.
Fonner  VA, Dalglish  SL, Kennedy  CE,  et al.  Effectiveness and safety of oral HIV preexposure prophylaxis for all populations.  AIDS. 2016,30(12):1973-1983. PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close