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Assessment, treatment, and follow-up recommendations for people with known or potential exposures to HIV and other infections. Health care providers should evaluate persons rapidly for nPEP when care is sought ≤72 hours after an exposure that presents a substantial risk for HIV acquisition.

Risk Assessment

*Some clinicians would offer nPEP on a case-by-case basis

Substantial Risk for HIV Acquisition

Exposure of: vagina, penis, rectum, eye, mouth or other mucous membrane, non-intact skin, or percutaneous contact
With: blood, semen, vaginal secretions, rectal secretions, breast milk, any body fluid that is visibly contaminated with blood
When: the source is known to have HIV

Negligible Risk for HIV Acquisition

Exposure of: any body part
With: urine, nasal secretions, saliva, sweat, tears (if visible blood, see “Substantial Risk for HIV Acquisition”)
When: regardless of the known or suspected HIV status of the source

Laboratory Assessment

  • HIV Ag/Ab: Rapid (point of care) antigen/antibody (Ag/Ab) combination test is preferred, but if not available, a non-rapid lab-based HIV Ag/Ab combination test alone should be done. If only non-rapid testing is done, start nPEP immediately and arrange follow-up in 1-2 days for HIV results. Consider also sending an HIV NAT if the person has recently taken oral antiretrovirals or had a cabotegravir injection for PrEP during the past year.
    • If the rapid HIV test is reactive (positive), the person does not need nPEP, but should be informed and offered immediate antiretroviral therapy and linked to ongoing HIV care (before being discharged).
    • Oral fluid–based rapid HIV tests are not recommended for HIV screening for nPEP.
  • Gonorrhea (GC) and chlamydia (CT) NAAT: Offer tests according to sites of sexual contact (e.g., swabs for oropharyngeal, rectal, vaginal sites; urine for urethral site).
    • For post-sexual assault patients, STI testing should be considered; empiric treatment should be provided whether or not STI testing is done.
  • Syphilis test: RPR/VDRL or treponemal test
    • For post-sexual assault patients, STI testing should be considered; empiric treatment should be provided whether or not STI testing is done.
  • Urine pregnancy test for persons at risk of pregnancy
  • Serum creatinine, ALT, AST
  • Hepatitis B sAb, cAb, sAg
  • Hepatitis C Ab

Treatment

Adults and adolescents (≥ 13 years) see below. Regimens for children and people with reduced renal function are also available. For any questions contact the National Clinician Consultation Center PEPline.

If rapid HIV Ag/Ab combination testing result is negative (non-reactive), or if lab-based test is sent and is pending, offer nPEP and as appropriate, STI treatment, emergency contraception, hepatitis B prophylaxis, mpox and HPV vaccination:

HIV prophylaxis: Administer first dose of nPEP on site as soon as possible after a negative rapid HIV test result is obtained or a non-rapid HIV test is sent.

  • bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF) (Biktarvy) 1 tablet PO daily x 28 days OR
  • dolutegravir (DTG) 50mg + tenofovir alafenamide (TAF) 25mg/emtricitabine (FTC) 200mg (Descovy) 1 tablet PO daily x 28 days OR
  • dolutegravir (DTG) 50mg + tenofovir disoproxil fumarate (TDF) 300mg/emtricitabine (FTC) 200mg (Truvada) 1 tablet of each PO daily x 28 days
  • Truvada should not be used for those with CrCl less than 60 mL/min; an alternative regimen must be used in those circumstances.

Sexually transmitted GC, CT, and trichomonas empiric treatment: offer to all patients post-sexual assault and consider for others with sexual exposures (oral, vaginal, or rectal exposures)

  • GC: Ceftriaxone (500 mg IM x 1 [1,000 mg IM for persons weighing ≥ 150 kg]) is the recommended treatment for GC and should not be substituted with another antibiotic unless there are clear contraindications (see CDC 2021 STI Treatment Guidelines for alternative).
  • CT: doxycycline 100 mg PO twice/day x 7 days (or if pregnant, azithromycin 1 gram PO x 1)
  • If risk of vaginitis: metronidazole 500mg PO twice daily x 7 days
  • Emergency contraception: Offer to persons at risk of pregnancy with a negative pregnancy test.
  • Hepatitis B prophylaxis: Administer 1 dose of hepatitis B vaccine to persons not previously vaccinated or incom­pletely vaccinated. If the exposure source is available for testing and is HBsAg positive, unvaccinated exposed persons should be given both hepatitis B vaccine and hepatitis B immune globulin during the initial nPEP evalu­ation. Follow-up dose(s) of hepatitis B vaccine should be administered according to the vaccine prescribing informa­tion. Previously vaccinated exposed persons who did not receive postvaccination testing should be provided a single hepatitis B vaccine booster dose.
  • Prophylaxis against hepatitis C is not recommended.
  • HPV vaccination: For those aged 9 to 45 years inclusively, offer HPV vaccination dose if not adequately vaccinated previously (see Gardasil package insert).
  • Mpox vaccination: Offer to anyone with a known or suspected exposure to mpox and to men who have sex with men.

Patient Education

  • Possible nPEP drug side effects: nausea, GI upset, headache, myalgias
  • Possible nPEP drug interactions: antacids, calcium, iron supplements
  • Stress the importance of adherence to the nPEP regimen for 28 days, without interruption
  • For those with ongoing risk of HIV infection, offer PrEP initiation immediately after completion of the 28-day course of nPEP
  • For men who have sex with men, consider offering a doxy-PEP prescription, a single 200 mg dose of doxycycline taken within 72 hours of condomless sex to reduce the risk of syphilis, chlamydia and gonorrhea transmission

Follow-up

  • Contact should be made within 24 hours to confirm access to nPEP medications and to assess tolerability and adherence, and follow up arrangements should be made for 4-6 weeks after initiating nPEP
  • HIV Ag/Ab combination and NAT HIV testing after initial non-reactive test
  • Syphilis test at 4-6 weeks and 3-6 months after exposure
  • HBV and HCV serology tests at 6 months after initial non-reactive test if susceptible at baseline

References and Resources

Primary resource
Non-Occupational Post-Exposure Prophylaxis (nPEP) Toolkit