Post-exposure prophylaxis

Christopher J. Hoffmann, M.D., M.P.H., Michael Melia, M.D.

DEFINITION

  • Exposure to HIV is a medical emergency. post-exposure prophylaxis (PEP) should be initiated within 2 hours and no later than 72 hours after exposure.
  • Often classified as occupational (oPEP; e.g., needlestick), non-occupational (nPEP; sexual exposure or injection drug use)

INDICATIONS

Risk of Transmission

  • Factors associated with transmission risk:
    • Viral load of source (sexual transmission does not occur with an undetectable viral load)
    • Volume of fluids from source (volume of blood - increased volume from hollow-bore needle)
    • Type of fluid: blood and/or visibly bloody fluids > seminal and vaginal secretions > cerebrospinal, synovial, pleural, peritoneal, pericardial, and amniotic fluids.
      • Fluids extremely unlikely to be infectious (unless visibly bloody): feces, nasal secretions, saliva, sputum, sweat, tears, urine, vomitus
    • Surface of exposure: direct inoculation into blood, rectal or genital mucosa, mucosa with trauma or visible bleeding pose greatest risk; low to no risk from intact skin
  • Occupational exposures
    • Estimated 600,000-800,000 percutaneous injuries within U.S. hospitals annually
    • Estimated risk of transmission: 0.2-0.3% per needlestick exposure; 0.03-0.09% per mucous membrane exposure (assuming an elevated viral load in the person with HIV)
    • Reported occupational transmissions now exceptionally rare: Whereas 58 confirmed and 150 possible cases of occupationally acquired HIV infection among healthcare workers were reported to CDC 1985-2013, only one case has been reported since 1999.
  • Non-occupational exposure risks when person with HIV has an elevated viral load (when viral load is < 200 there is no risk from sexual exposure)
    • Needle sharing IDU 63/10,000 (0.63%) per exposure
    • Discarded needles with no blood or dried blood - low to no risk for HIV transmission
    • Receptive anal intercourse 138/10,000 (1.38%) per exposure
    • Receptive vaginal intercourse 8/10,000 (0.08%) per exposure
    • Insertive anal intercourse 11/10,000 (0.11%) per exposure
    • Insertive vaginal intercourse 4/10,000 (0.04%) per exposure
    • Receptive and insertive oral intercourse - very low
    • Biting or spitting - negligible risk
    • Kissing - no risk

Testing Source

  • Rapid test: Preferred for oPEP. Use when source person HIV status unknown. Result available in ≤1 hr, highly reliable in ruling out HIV, cost effective, and reduces HCW anxiety. Discontinue PEP if source patient testing is negative.
  • Standard testing for oPEP: ELISA usually available within 72 hrs. Do not wait for result before starting PEP. Discontinue PEP if negative.
  • If acute seroconversion suspected in source, check viral load. This approach should be needed infrequently. Initiate PEP while awaiting test result
  • Source testing usually not possible with nPEP

CLINICAL RECOMMENDATION

Efficacy and Duration of PEP (Post-Exposure Prophylaxis)

  • Exposure to HIV is a medical emergency. PEP should be initiated within 2 hours and no later than 72 hours after exposure. Once PEP is initiated, it can be stopped should further evaluation of the exposure determine low or no risk of HIV exposure.
  • Animal data show that PEP initiated < 24 hrs after exposure and extended for 28 days effective in preventing transmission of HIV. One wk PEP less effective than 4 wks course.
  • Retrospective case-control study showed 81% reduction in HIV transmission risk with AZT monotherapy. Currently available combination therapy likely more effective, although no data.

Selection of PEP Agents

  • Preferred: TAF/FTC/BIC given potency, favorable side effect profile, once-daily dosing, low resistance risk, anticipated effectiveness, and single-tablet regimen
  • TDF/FTC + DTG given potency, favorable side effect profile, once-daily dosing, low resistance risk, and anticipated effectiveness (use TAF instead of TDF if impaired kidney function)
  • Many other choices reasonable but limited by side effects, more-than-daily dosing, food or medication restrictions, and/or lack of experience as PEP
  • Not recommended:
    • AZT/3TC requires twice-daily dosing and is associated with considerable side effects.
    • Do not use ABC/3TC because of possibility of life-threatening abacavir hypersensitivity reaction.
    • Do not use NVP because of risk of life threatening hepatotoxicity in pts with normal CD4 counts
  • If high concern or known drug resistance select regimen based on known resistance. One initial option may be TDF/FTC + DTG + DRV + rtv while consulting HIV expert (National Clinicians’ PEP Hotline: 888-448-4911) to assist in selection of drugs to which source’s virus unlikely to be resistant. Important to rapidly obtain information on source treatment history and genotypes, if available.
  • Drug-drug interactions must be reviewed.

Drugs for PEP

  • TDF: Potent, well tolerated, once-daily dosing; effective for PEP in primate studies; do not dose daily if eGFR < 60.
  • TAF may generate lower mucosal tenofovir levels than TDF, so some prefer TDF > TAF, particularly for nPEP, although efficacy of TAF for PrEP among MSM reassuring
    • Toxicity concerns favoring TAF over TDF in PLWH do not apply to PEP/nPEP given short duration of therapy
  • FTC: Daily, similar to 3TC, available coformulated with TDF (Truvada).
  • RAL: Potent, well-tolerated; twice-daily dosing; no food requirement; recommended in combination with TDF/FTC by USPHS
  • DTG: Potent, well-tolerated; once-daily dosing.
  • 3TC: Potent, well tolerated, available in coformulation with AZT (Combivir).
  • BIC Potent, well-tolerated; once-daily dosing. Limited experience.
  • NVP: DO NOT USE in PEP as 22 HCWs had serious adverse reactions (12 hepatotoxicity including 1 liver transplant, 14 skin reactions including Stevens-Johnson syndrome) (U.S. Public Health Service).

Monitoring and Counseling: All

  • HIV serology (ideally via rapid test) at presentation and again at 6 wks, 12 wks, and 6 mos. Perform at 12 mos if HCV acquired with injury.
    • If fourth-generation combination HIV p24 antigen-HIV Ab test used, testing at baseline, 6 wks, and 4 mos sufficient.
    • If rapid testing not available, do not delay initiation of PEP if it is otherwise indicated.
  • Clinical assessment and laboratory tests (CBC and metabolic profile, including assessment of glucose and renal and hepatic functions) prior to initiation and at week two of PEP.
  • Clinical assessment within 72 hours after starting PEP. Prescribe supportive-care meds (e.g., anti-emetics) if needed.
  • Pregnancy: does not preclude PEP.
    • All listed preferred PEP agents are safe for use during pregnancy.
  • Breastfeeding: Not a contraindication to PEP.
  • Blood and tissue donation: Avoid until final HIV test negative.
  • Prevent sexual transmission: Safe sex or abstain until final HIV test negative. Greatest risk in first 6-12 wks post exposure.
  • Advise HCW to seek medical care for any new symptoms while on PEP and/or for any acute illness that occurs during follow-up period. Risk of seroconversion highest within first 6-12 wks post injury.
  • Do not neglect the possibility that the patient may need mental health care regarding his/her exposure.

Adjunctive Treatment, Monitoring, and Counseling: oPEP

  • For cutaneous breaches, the exposed skin should be cleansed with soap and water. Alcohol-based cleansers (virucidal) should also be used for small wounds and punctures.
  • Exposed mucous membranes should be flushed with water or saline.
  • Initiation of PEP: As quickly as possible, ideally with 2 hrs of injury. Benefits likely diminish significantly >24-36 hours after exposure. PEP typically not recommended if ≥72h post-exposure, although guidelines suggest PEP might be considered up to one week after extremely high-risk exposures (e.g., percutaneous injury with a needle that had been in a blood vessel of an HIV-infected patient).

Adjunctive Treatment, Monitoring and Counseling: HCW

  • Employee/occupational health service should be contacted regarding all exposures to potentially contaminated fluids.
  • For cutaneous breaches, the exposed skin should be cleansed with soap and water. Alcohol-based cleansers (virucidal) should also be used for small wounds and punctures.
  • Exposed mucous membranes should be flushed with water or saline.
  • Screen for HBV at baseline, 4-6 wks after exposure, and then 3-4 months after exposure.
  • Screen for HCV at baseline, 3-4 mos after exposure, and then 6 mos after exposure. Confirm positive serology with PCR.

Adjunctive Treatment, Monitoring and Counseling: nPEP

  • Risk reduction strategies (e.g., sexual abstinence, consistent condom use, avoidance of sharing injection drug use paraphernalia) should be stressed.
  • Patients who receive ≥1 courses of nPEP should be considered for PrEP.
  • Consider emergency contraception as appropriate.
  • Pregnancy test at baseline and then 6 wks and 3 mos after exposure if woman of childbearing potential with sexual exposure.
  • Screen for HBV at baseline, 4-6 wks after exposure, and then 3-4 months after exposure.
  • Screen for HCV at baseline, 3-4 mos after exposure, and then 6 mos after exposure. Confirm positive serology with PCR.
  • Screen for syphilis by serology and gonorrhea & chlamydia by site of exposure during initial evaluation (or soon thereafter) and approximately 6 wks after exposure.

Hepatitis B Post-Exposure Prophylaxis

  • Exposed individual unvaccinated and source HBsAg+ or unknown: HBIG x1 + vaccine series (3 doses). Check post-vaccine serology.
  • Exposed individual unvaccinated and source negative: vaccine series (3 doses). Check post-vaccine serology for vaccine response.
  • Exposed individual vaccinated and known to be a responder (antibody to HBsAg >10 mIU/mL): No treatment.
  • Exposed individual previously HBV-infected (antibody to HBsAg >10 mIU/mL): No treatment.
  • Exposed individual vaccine non-responder and source HBsAg+ or unknown: HBIG x2 (one month apart).
  • Exposed individual antibody status unknown: Test for anti-HBs.
    • If anti-HBs ≥10 mIU/mL: no action needed.
    • If anti-HBs < 10 mIU/mL and source HBsAg+ or unknown: HBIG x1 + vaccine series (3 doses). Check post-vaccine serology.
    • If anti-HBs < 10 mIU/mL and source negative: vaccine series (3 doses). Check post-vaccine serology.

Hepatitis C Occupational Exposure

  • If HCV antibody positive obtain HCV RNA. If active infection indicated by detectable HCV RNA, follow recommendations for acute HCV (generally delayed treatment initiation)

Useful Management Resources

OTHER INFORMATION

  • Report all cases of suspected occupationally acquired HIV infection in healthcare workers to state health department HIV surveillance staff and the CDC Coordinator for Cases of Public Health Importance, Division of HIV/AIDS Prevention, at 404-639-0934 or 404-639-2050.

Basis for recommendation

  1. Kuhar DT, Henderson DK, Struble KA, et al. Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis. Infect Control Hosp Epidemiol. 2013;34(9):875-92.  [PMID:23917901]

    Comment: Updated recommendations to include the use of three-drugs for all persons for whom PEP is indicated

References

  1. Billick MJ, Fisher KN, Myers S, et al. Brief Report: Outcomes of Individuals Using HIV Postexposure Prophylaxis-In-Pocket ("PIP") for Low-Frequency, High-Risk Exposures in Toronto, Canada. J Acquir Immune Defic Syndr. 2023;94(3):211-213.  [PMID:37850980]
  2. Mayer KH, Gelman M, Holmes J, et al. Safety and Tolerability of Once Daily Coformulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide for Postexposure Prophylaxis After Sexual Exposure. J Acquir Immune Defic Syndr. 2022;90(1):27-32.  [PMID:34991141]
  3. Bekerman E, Cox S, Babusis D, et al. Two-dose emtricitabine/tenofovir alafenamide plus bictegravir prophylaxis protects macaques against SHIV infection. J Antimicrob Chemother. 2021;76(3):692-698.  [PMID:33202006]

    Comment: Demonstration of the effectiveness of 4 weeks FTC/TAF/BIC in Macaque model of HIV exposure.
    Rating: Important

  4. Chauveau M, Billaud E, Bonnet B, et al. Tenofovir DF/emtricitabine/rilpivirine as HIV post-exposure prophylaxis: results from a multicentre prospective study. J Antimicrob Chemother. 2019;74(4):1021-1027.  [PMID:30689937]

    Comment: Observational, prospective, multi-center, open-label, non-randomized study in France. 163 courses of PEP prescribed for 150 sexual exposures, 13 non-sexual. Five stopped PEP owing to negative source HIV test. 136/158 (86%) of those who continued completed all 28d, highlighting tolerability of this (contemporary) regimen. No HIV seroconversions at 16w.

  5. Moore DL. Needle stick injuries in the community. Paediatr Child Health. 2018;23(8):532-546.  [PMID:30894792]
  6. Cresswell FV, Ellis J, Hartley J, et al. A systematic review of risk of HIV transmission through biting or spitting: implications for policy. HIV Med. 2018.  [PMID:29687590]
  7. Nwaiwu CA, Egro FM, Smith S, et al. Seroconversion rate among health care workers exposed to HIV-contaminated body fluids: The University of Pittsburgh 13-year experience. Am J Infect Control. 2017;45(8):896-900.  [PMID:28449921]
  8. Fätkenheuer G, Jessen H, Stoehr A, et al. PEPDar: A randomized prospective noninferiority study of ritonavir-boosted darunavir for HIV post-exposure prophylaxis. HIV Med. 2016;17(6):453-9.  [PMID:27166295]

    Comment: Open-label, randomized, multi-center, prospective study in Germany of DRV + rtv or LPV/r + 2 NRTI for PEP. No difference in early discontinuations or ADR between groups. Fewer DRV + rtv subjects (16%) had ≥1 grade 2-3 ADS vs 29% of LPV/r subjects (p = 0.006). No seroconversions reported.

  9. Joyce MP, Kuhar D, Brooks JT. Notes from the field: occupationally acquired HIV infection among health care workers - United States, 1985-2013. MMWR Morb Mortal Wkly Rep. 2015;63(53):1245-6.  [PMID:25577991]

    Comment: Updated data on risk of occupationally-acquired HIV infection, including confirmation of only one such case since 1999.
    Rating: Important

  10. Schillie S, Murphy TV, Sawyer M, et al. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm Rep. 2013;62(RR-10):1-19.  [PMID:24352112]

    Comment: Post-exposure HBV prophylaxis recommendations following occupational percutaneous and/or mucosal exposure to blood and body fluids
    Rating: Important

  11. Henderson DK. Management of needlestick injuries: a house officer who has a needlestick. JAMA. 2012;307(1):75-84.  [PMID:22146902]

    Comment: Comprehensive discussion of epidemiology and risk, prevention, management, treatment, and counseling for healthcare providers who sustain needlestick injuries, including above recommendation re: post-exposure HCV testing.

  12. Mayer KH, Mimiaga MJ, Gelman M, et al. Raltegravir, tenofovir DF, and emtricitabine for postexposure prophylaxis to prevent the sexual transmission of HIV: safety, tolerability, and adherence. J Acquir Immune Defic Syndr. 2012;59(4):354-9.  [PMID:22267017]

    Comment: Study of 85 evaluable participants given nPEP demonstrating improved side effect profile when compared with historical control of AZT/3TC plus ritonavir-boosted protease inhibitor.

  13. Landovitz RJ, Currier JS. Clinical practice. Postexposure prophylaxis for HIV infection. N Engl J Med. 2009;361(18):1768-75.  [PMID:19864675]

    Comment: Nice contemporary review of nPEP that highlights TDF/FTC or AZT/3TC PLUS ATV/r, DRV/r, or LPV/r as the medication combinations of choice for post-exposure prophylaxis. The authors favor use of nPEP if there is ≥0.1% risk of HIV transmission from an HIV-positive person or a person of unknown HIV-status at high risk for infection.

  14. Bryant J, Baxter L, Hird S. Non-occupational postexposure prophylaxis for HIV: a systematic review. Health Technol Assess. 2009;13(14):iii, ix-x, 1-60.  [PMID:19236820]

    Comment: Systematic review of nPEP studies through December 2007 which found that nPEP for male-male intercourse was cost effective and for IDUs sharing needles with known HIV-infected person. Studies however were of mixed or limited quality.

  15. Guinot D, Ho MT, Poynten IM, et al. Cost-effectiveness of HIV nonoccupational post-exposure prophylaxis in Australia. HIV Med. 2009;10(4):199-208.  [PMID:19207598]

    Comment: Retrospective cost analysis of nPEP in Australia. nPEP not found to be cost-effective except in the case of unprotected receptive anal intercourse.

  16. Kim JC, Askew I, Muvhango L, et al. Comprehensive care and HIV prophylaxis after sexual assault in rural South Africa: the Refentse intervention study. BMJ. 2009;338:b515.  [PMID:19286746]

    Comment: Descriptive paper about nurse-run PEP program for sexual assault exposures in S. Africa.

  17. Henderson DK. Managing occupational risks for hepatitis C transmission in the health care setting. Clin Microbiol Rev. 2003;16(3):546-68.  [PMID:12857782]

    Comment: Comprehensive and excellent review of Hepatitis C occupational exposure management.

  18. Do AN, Ciesielski CA, Metler RP, et al. Occupationally acquired human immunodeficiency virus (HIV) infection: national case surveillance data during 20 years of the HIV epidemic in the United States. Infect Control Hosp Epidemiol. 2003;24(2):86-96.  [PMID:12602690]

    Comment: Summarizes characteristics of the reported U.S. cases.

  19. Gerberding JL. Clinical practice. Occupational exposure to HIV in health care settings. N Engl J Med. 2003;348(9):826-33.  [PMID:12606738]

    Comment: Clinical practice review with some useful management resources.

  20. Sulkowski MS, Ray SC, Thomas DL. Needlestick transmission of hepatitis C. JAMA. 2002;287(18):2406-13.  [PMID:11988061]

    Comment: Case report and review.

  21. Braitstein P, Chan K, Beardsell A, et al. Safety and tolerability of combination antiretroviral post-exposure prophylaxis in a population-based setting. J Acquir Immune Defic Syndr. 2002;29(5):547-8.  [PMID:11981375]

    Comment: Discusses ARV tolerability.

  22. Quirino T, Niero F, Ricci E, et al. HAART tolerability: post-exposure prophylaxis in healthcare workers versus treatment in HIV-infected patients. Antivir Ther. 2000;5(3):195-7.  [PMID:11075939]

    Comment: Discusses ARV tolerability issues among HCW versus HIV+ pts identifying higher adverse effects among HCW than HIV+ pts.

  23. Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. N Engl J Med. 1997;337(21):1485-90.  [PMID:9366579]

    Comment: Sentinel retrospective case control study that identified benefit of AZT PEP.

  24. Smith DK, Grohskopf AL, Black RJ et al. Antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV in the United States: recommendations from the U.S. Department of Health and Human Services. Atlanta: Centers for Disease Control and Prevention, 2005. MMWR 1/21/05.

    Comment: DHHS guidelines on nPEP that provide and excellent, detailed discussion of the risks and benefits of nPEP followed by a recommended approach to persons seeking nPEP. These contain more background information than the 2005 Occupational Exposures guidelines.
    Rating: Important

  25. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1- Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. Accessed November 13, 2015. [Table 6, p. C-30]

    Comment: Recommended initial combination regimens for ART-naive, HIV-infected pregnant women; used as basis of above recommendations for PEP for pregnant women.

Post-exposure prophylaxisis the Johns Hopkins Guides Word of the day!

Last updated: September 13, 2025