PEP Quick Guide for Occupational Exposures

These NCCC post-exposure prophylaxis (PEP) recommendations will help you with urgent decision-making for occupational exposures to HIV and hepatitis B and C. Consultation can be obtained from Occupational Health or Employee Health Services, local experts, or the NCCC’s PEPline. See the PEPline page for current hours and availability. The CDC’s occupational post-exposure guidelines can be accessed on our PEP Guidelines page.

Commonly Asked Questions

Initial Evaluation: Assessing Exposures and Testing

What immediate measures should be taken?
• Lightly wash needlestick/cut exposed area with soap and water
• Flush splashes to the nose, mouth, or skin with water
• Irrigate eyes with clean water, saline, or sterile irrigants

What is considered to be a potential exposure to HIV, HBV or HCV?
For transmission of blood borne pathogens (HIV, HBV and HCV) to occur, an exposure must include both of the following:
• Infectious body fluid: Blood, semen, vaginal fluid, amniotic fluid, breast milk, cerebrospinal fluid, pericardial fluid, peritoneal fluid, pleural fluid and synovial fluid can transmit HIV, HBV and HCV.

• Note that saliva, vomitus, urine, feces, sweat, tears and respiratory secretions do not transmit HIV (unless visibly bloody). The risks of HBV and HCV transmission from non-bloody saliva are considered to be negligible.

The PEPline does not recommend routine HIV, HBV or HCV surveillance testing following exposure or possible exposure to non-bloody saliva.*

* Federal guidelines consistently emphasize that non-bloody saliva does not carry risk for transmitting HIV, stating that non-bloody saliva is not considered infectious for HIV. The federal guidelines on HBV and HCV are not as clear. They emphasize that certain non-bloody fluids, including saliva, are unlikely to transmit those viruses (various terms are used in the different guidelines), but do not make specific recommendations regarding follow-up testing. In the absence of clear federal guidelines on follow-up HBV and HCV testing following non-bloody saliva exposures, the PEPline recommendation, above, has taken many factors into consideration. Advantages of follow-up testing include: (1) reassurance for exposed persons who need additional confirmation; (2) documentation of the lack of transmission to confer liability protection; and (3) conformity with local regulations (e.g., state, hospital, or practice protocols/guidelines). Disadvantages of follow-up testing include: (1) increasing confusion and stress from the contradictory messages that the exposure does not confer transmission risk yet months of follow-up testing is to be performed; (2) addressing potential false positive test results, which create personal distress and additional healthcare costs; (3) possibly increasing work-related stress and stress-related health conditions; (4) creating a period of modified sexual practices/interactions and family planning in certain instances; and (5) increasing overall healthcare costs and time away from work. Because the transmission risk of HBV and HCV in exposures to non-bloody saliva, if any, is considered to be negligible and the disadvantages listed above are important, the PEPline does not routinely recommend follow-up testing, but does not take the position that such testing should not occur.

• A portal of entry (percutaneous, mucous membrane, cutaneous with non-intact skin)
If both of these factors are not present, there is no risk of blood borne pathogen transmission and further evaluation is not required.

What baseline testing should be performed after an exposure?
Source Person (SP):
• HIV Ag/Ab or HIV Ab (rapid HIV testing preferred if accessible)*
• HCV Ab or HCV RNA (“HCV viral load”)
• Testing for HBsAg (HBV surface antigen) alone is sufficient to inform management of exposed HCP. If possible, consider comprehensive HBV screening of source persons to help facilitate increased HBV screening in general.
* If SP’s rapid HIV test is positive, assume this is a true positive for purposes of initial PEP decision-making, and send confirmatory/supplemental testing.
Exposed Person (EP): If no blood borne pathogen exposure occurred, or SP is confirmed negative on baseline testing, no baseline testing is clinically indicated for the EP. Testing can be considered for other purposes, including medicolegal concerns or as per institutional protocols. For bites, see “How should a human bite be managed?”
• HIV Ag/Ab or HIV Ab
• HCV Ab (if positive, follow-up with HCV RNA testing)
• HBV testing: Depends on immunization status.
Note that most healthcare and public safety personnel have been vaccinated against hepatitis B. If previously vaccinated and they know they responded to the vaccine series (a positive titer after completion of either a 2- or 3-dose vaccine series is ≥ 10mIU/mL), they are considered to have lifelong immunity and require no further testing or treatment. Similarly, if employee health records indicate they responded to the vaccination series, they are considered immune. For all others, see the “Exposures to HBV” section of this guide.

Is a rapid HIV test accurate enough to decide on whether to give PEP?
Rapid HIV tests are generally very sensitive and specific and can be used to determine whether to offer PEP. A positive rapid HIV test should be preliminarily considered a true positive for the purposes of initial PEP decision-making. A negative rapid test should be considered a true negative. Investigation of whether a source might be in the “window period” is unnecessary for determining whether HIV PEP is indicated unless acute HIV (acute retroviral syndrome) is clinically suspected.

Deciding Whether to Give HIV PEP

What is the time frame for using PEP?
Efficacy is time sensitive: the first dose should be given as soon as possible. Optimal time to start PEP is within hours of exposure, rather than days. Do not wait for SP test results (unless results will be available within an hour or two) to proceed with a PEP decision and initiation, when indicated. The PEPline considers 72 hours post-exposure as the outer limit of opportunity to initiate PEP; however, a delay of that scale is believed to compromise PEP efficacy. The 72-hour outside limit recommendation is based on animal studies; no human data are available that establishes the outer limit of PEP effectiveness. Consultation with the PEPline or an expert in post-exposure prophylaxis is recommended if considering PEP initiation beyond 72 hours.
* Note: PEP should be initiated as soon as possible. If additional information subsequently becomes available that the source person is HIV negative, PEP can always be discontinued.

What is the risk of HIV transmission?

* Note: These estimates are from exposures to blood from HIV-positive source persons; risk for transmission from infectious fluids other than blood is probably considerably lower than for blood exposures.

Is PEP always recommended if the source person is HIV positive?
PEP is typically recommended when an exposure to an HIV positive patient has occurred.
(See “What is considered to be a potential exposure to HIV, HBV or HCV?”)
• Although the decision-making and risk context for occupational PEP differs from non-occupational PEP, studies analyzing more than 90,000 sexual encounters have shown that transmissions from persons with undetectable HIV viral load did not occur. The PEPline therefore does not always recommend PEP following exposures involving source persons with recent undetectable viral load, as the risks of PEP (although few) are anticipated to be greater than benefits. To allow for person-centered, shared decision-making, exposed persons who remain concerned and wish to start PEP should not be denied PEP. Initiation of PEP should not be delayed if the source person’s viral load and/or HIV treatment information or consultation is not immediately available.

Is PEP recommended if the source person has an unknown HIV status?
PEP is generally not warranted in cases of unknown status. However, consider PEP for exposures from a source with HIV risk factors. The decision to take PEP should be individualized following a shared decision-making process based on accurate risk assessment, the treating clinician’s recommendations, and patient preferences. If questions exist, seek expert consultation.

Is PEP recommended if the source person is unknown (e.g. sharps box injury)?
PEP is generally not warranted when the source person is unknown. However, consider PEP on a case by case basis. The decision to take PEP should be individualized following a shared decision-making process based on accurate risk assessment, the treating clinician’s recommendations, and patient preferences. If questions exist, seek expert consultation.

Should PEP be given if it is uncertain whether the exposure constitutes a significant risk?
If consultation is not available within a few hours, PEP can be started pending consultation. Timely and comprehensive assessment is key, and PEP can be discontinued later if the final decision is that PEP is not warranted.

What if the source person might be in the “window period” for HIV?
If the source person’s HIV test is negative at the time of the exposure, they are generally considered uninfected and PEP is not recommended.
• The “window period” for HIV Ab seroconversion (the period between initial HIV acquisition and development of detectable HIV antibodies) can cause patient and provider anxiety. No instances of occupational transmission during the window period have been detected in the United States to date.
• Therefore, investigation of whether a source person might be in the “window period” is unnecessary for determining whether HIV PEP is indicated unless acute HIV is clinically suspected, or recent (within the previous 1-2 months) high-risk exposure has occurred. If acute HIV is suspected, PEP should be started while an HIV RNA PCR (“HIV viral load”) is sent from the source person. Note that only about 50-60% of persons with acute HIV develop symptoms (typically presents as a non-specific viral syndrome 2-10 weeks after infection).

Is PEP recommended for a patient who was stuck with a sharp device (e.g. needle, razor) from an unknown source outside of a healthcare setting?
This common occurrence falls into the classification of possible exposure to blood/body fluid from an unknown source. A “found needle” is the classic occurrence. No cases of HIV transmission from a “found needle” outside of a healthcare setting in the United States have been documented. Therefore, the PEPline generally discourages PEP in these cases. Even within healthcare settings, “found needles” have only been implicated in two cases of transmission over the past two decades.

How should a human bite be managed?
• Human bites can result in exposures to both the biter and the bitten person. The bitten sustains a cutaneous exposure if blood was present in the mouth of the biter before the bite. The biter sustains a mucous membrane exposure if blood from the bitten person enters the oral cavity of the biter.
• If the saliva is non-bloody, there is no HIV transmission risk to the bitten. The PEPline does not recommend routine HIV, HBV or HCV surveillance testing following exposure or possible exposure to non-bloody saliva. (See above)

HIV PEP: What to Give

How to choose a PEP regimen?
Three-drug PEP regimens are now the recommended regimens for all exposures. There are some special circumstances in which a two-drug regimen can be considered/used, especially when recommended antiretroviral medications are unavailable or there is concern about potential toxicity or adherence difficulties. Consultation is recommended if a two-drug regimen is considered. In addition, the Guidelines state, “PEP is not justified for exposures that pose a negligible risk for transmission.” Consultation with an expert can help determine if the exposure poses a “negligible risk” to explore whether alternative approaches, including a modified regimen, are appropriate.

PREFERRED 3-DRUG HIV PEP REGIMEN:

PLUS

Raltegravir (Isentress®; RAL) 400mg by mouth twice daily
or
Dolutegravir (Tivicay™; DTG) 50mg by mouth once daily*

Duration: 28 days

Side effects and drug-drug interactions: See below

How long is PEP taken?
PEP is taken for 28 days. If source person testing is negative for HIV, PEP should be stopped.

How to monitor and manage side effects of PEP?
Side effects are generally self-limited, but occasionally can limit PEP adherence. Gastrointestinal side effects (nausea, upset stomach, vomiting, and diarrhea) are most common. Headache, fatigue, and insomnia can also occur. Antiemetic and antidiarrheal medications can help support PEP medication adherence. If side effects are severe, consider changing to a different regimen. Toxicities are rare with the current preferred PEP regimens, generally not life-threatening, and are reversible once PEP medications are stopped.

The most important concern with the preferred regimen, tenofovir DF/emtricitabine plus raltegravir or dolutegravir, is potential renal toxicity from tenofovir DF. This regimen should be used with caution in persons with impaired renal function or who are at high risk for impaired renal function.

Lab monitoring for drug toxicity: Check CBC, renal and hepatic function tests at baseline and two weeks after starting PEP.

What are common drug-drug interactions between PEP and the exposed person’s medications?
There are important drug interactions between polyvalent cations (calcium⁺⁺, aluminum⁺⁺, magnesium⁺⁺, Fe⁺⁺) and both raltegravir and dolutegravir. Raltegravir can be co-administered with calcium-containing antacids (e.g., CaCO₃), but should not be co-administered with aluminum- or magnesium-containing antacids (e.g., most antacids), laxatives (milk of magnesia, etc.) or supplements. Dolutegravir should be given two hours before or at least six hours after either aluminum- or magnesium-containing antacids, laxatives or supplements; dolutegravir can be co-administered with calcium-containing antacids or with Fe⁺⁺ but only if taken together with food. Consult the PEPline or a PEP-experienced clinical pharmacist/clinician for additional questions on drug-drug interactions.

ALTERNATIVE REGIMENS FOR PATIENTS WITH RENAL DYSFUNCTION (creatinine clearance ≤ 59mL/min): Zidovudine plus lamivudine (co-formulated as Combivir®) PLUS raltegravir or dolutegravir. See raltegravir and dolutegravir caution, above.

ALTERNATIVE REGIMENS*
May combine one drug or drug pair from the left column with one pair of nucleoside/nucleotide reverse transcriptase inhibitors from the right column.

* The alternative regimens are listed in order of USPHS preference. Newer antiretroviral medications have become available since the USPHS occupational PEP guidelines were updated in 2013, and other alternatives using these newer medications may be reasonable based upon patient and clinician preference.

Note: For additional information on dosing, drug-drug interactions and toxicities, and toxicity monitoring, see the antiretroviral drug tables found in the Pharmacy section of the NCCC website.

ARV drug dosing and toxicity monitoring *

* Note: For additional information on dosing, drug-drug interactions and toxicities, and toxicity monitoring, see the antiretroviral drug tables found in the Pharmacy section of the NCCC website.

Pregnancy and Breastfeeding

How should HIV exposures in pregnant people be managed?
• Starting PEP in pregnant exposed persons should be based on considerations similar to those of non-pregnant exposed persons.
• When deciding to start PEP, a pregnant exposed person should discuss with the treating clinician the potential risks of fetal exposure to antiretroviral (ARV) medications.
• All pregnant people starting ARVs should be entered in the Antiretroviral Pregnancy Registry, a database designed to collect information on the outcomes of ARV-exposed pregnancies regardless of HIV status: http://apregistry.com.

Special considerations
• The pregnant exposed person and fetus are at risk for HIV acquisition.
• Acute HIV in pregnancy incurs a high risk of perinatal transmission.
• Use of most PEP medications can be justified when the benefits of PEP are believed to outweigh the potential risk of infant (and maternal) ARV exposure.
• Based on limited data, use of ARVs in pregnancy, including in the first trimester, does not appear to increase the risk of birth defects compared to the general population.
• Toxicities from currently recommended PEP medications are not thought to be increased in pregnancy.

PEP options for persons who are pregnant or breastfeeding
Options include:

or

PLUS EITHER

Darunavir (Prezista®, DRV) 800mg once daily# boosted with ritonavir (Norvir®, RTV) 100mg daily #

Atazanavir (Reyataz®, ATV) 300mg # once daily boosted with ritonavir (Norvir®, RTV) 100mg daily

# Due to PK changes, current DHHS Perinatal Guidelines recommend increasing to DRV 600mg twice daily boosted with RTV 100mg twice daily for all pregnant persons. Atazanavir should be increased to 400mg daily in the 2nd and 3rd trimesters (and continue to boost with ritonavir 100mg daily).

Other PEP options can be considered in the event of intolerance, source persons with resistant virus, medication access challenges, or EP preference. In these instances, providers should seek expert consultation.

How should HIV exposures in lactating exposed persons be managed?
• Breastfeeding is not a contraindication for PEP.
• When deciding to start PEP, lactating exposed persons should discuss with the treating clinician the potential risks and benefits of infant exposure to antiretroviral (ARV) medications through breast milk. The decision to take PEP and/or continue breastfeeding is complex and individualized. Expert consultation is available.

Special considerations:
• The lactating exposed person and infant may be at risk for HIV acquisition.
• Acute HIV in a breastfeeding person greatly increases the risk of HIV transmission to the breastfed infant.
• There are limited data on PEP medications in breast milk (details are available in Appendix B: Supplement: Safety and Toxicity of Individual ARV Agents in Pregnancy, DHHS Perinatal Guidelines):
– Tenofovir DF (TDF, component of Truvada™) can occasionally be detected in breast milk and breastfed infants in very limited amounts.
– Lamivudine (3TC, Epivir®) and emtricitabine (FTC, component of Truvada™) can be detected in breast milk and breastfed infants, at levels that are a small fraction of the therapeutic dose used for treatment of HIV.
– Raltegravir (RAL, Isentress®) – Whether RAL is secreted in human breast milk is unknown. One case study of a breastfeeding woman taking RAL showed detectable levels in breast milk but no detectable levels in her breastfed infant.
– Dolutegravir (DTG, Tivicay®) – Low levels have been detected in breast milk and breastfed infants.
• For breastfeeding people who choose to take PEP, pumping and discarding is an option to allow continuation of lactation while preventing infant ARV and (possible) HIV exposure.
• For breastfeeding people who do not take PEP, pumping and storing breast milk while waiting for the source person’s HIV testing results is an option. This allows continuation of lactation while not exposing infants (and breastfeeding people) to PEP medications or potentially to HIV.

Exposures to HBV

How are exposures to HBV managed?
• If the source person is HBsAg negative, no hepatitis B testing or post-exposure treatment of the exposed HCP is needed.
• For source persons of unknown HBV status, testing for HBsAg (HBV surface antigen) alone is sufficient to inform management of exposed HCP. If possible, consider comprehensive HBV screening of source persons to help facilitate increased HBV screening in general.
• If the exposed person is known to be immune (e.g., they were told they had a positive response to a complete HBV vaccine series, indicated by post-vaccination HBsAb titer ≥10 mIU/mL), they are considered to have lifelong immunity and need no additional hepatitis B testing or post-exposure treatment.
• If the source person is known to have hepatitis B or the source person’s hepatitis B status is unknown, manage exposures or potential exposures as follows:

Recommendations for Post-Exposure Prophylaxis After HBV Exposure

EXPOSED PERSON VACCINATION STATUS	TEST RECOMMENDED FOR EXPOSED PERSON	TREATMENT
Previously Vaccinated
Responder after complete series 1 (HBsAb ≥10 mIU/mL)	None	No action needed
Response unknown after complete series 1	HBsAb	If HBsAb ≥10mIU/mL: No action needed If HBsAb
HBsAb	HBcAb (total)	HBIG 3 x 1 and revaccinate
Non-responder (HBsAb	HBcAb (total)	HBIG 3 x 2 (one month apart)
Unvaccinated or Incompletely Vaccinated
Unvaccinated or incompletely vaccinated 2	HBcAb (total)	HBIG 3 x 1 and vaccinate/revaccinate
1 The complete 3-dose HBV vaccine series is usually given at baseline, 1 month, and 6 months. Alternatively, a complete series with Heplisav-B recombinant vaccine is given as two injections at least 4 weeks apart. Follow-up testing confirms immunity if HBsAb ≥10mIU/mL. For persons previously immunized with a complete series but have a negative ( 3 HBIG: 0.06mL/kg IM, give as soon as possible. Studies are limited on the maximum interval after exposure during which post-exposure prophylaxis is effective, but the interval is unlikely to exceed 7 days for percutaneous exposures or 14 days for sexual exposures. Note: Testing the exposed HCP for prior HBV infection is not required before vaccinating unless the exposed is at independent risk of HBV infection (e.g., from an HBV endemic area). Adapted from: CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR: December 20, 2013. See also: Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2018; 67 (1): 1-31. How soon do hepatitis B vaccine and HBIG need to be given? In general, if hepatitis B vaccine and/or HBIG are required, the sooner they are administered the better. The effectiveness of HBIG when given after 7 days for occupational exposures is unknown. Exposures to HCV How are exposures to HCV managed? • The risk of HCV transmission after percutaneous exposure is ~0.2% (2 out of 885) and 0% (0 out of 458) after mucocutaneous exposure when the source patient has HCV infection (Egro FM, Nwaiwu CA, Smith S. Seroconversion rates among healthcare workers exposed to hepatitis C virus-contaminated body fluids: The University of Pittsburgh 13-year experience. Am J Infect Control 2017; 45: 1001-5.). • Post-exposure prophylaxis is not currently available/approved following an exposure to HCV. • Testing for HCV is based on the following sequence: Most persons who acquire HCV infection will have a positive HCV RNA within 1-2 weeks of exposure; antibodies to HCV (anti-HCV or HCV Ab) generally appear 8-11 weeks after exposure. • Testing recommendations for source persons and exposed persons have been updated (July 2020): Testing and Clinical Management of Health Care Personnel Potentially Exposed to Hepatitis C Virus — CDC Guidance, United States, 2020. MMWR Recomm Rep 2020;69(No. RR-6):1–8. https://www.cdc.gov/mmwr/volumes/69/rr/rr6906a1.htm • The following is a PEPline Quick Guide summary of those recommendations: Recommendations for HCV Testing Following Occupational Blood-Borne Pathogen Exposure Source Person Testing 1 Source Person Status Test(s) HCV-positive (known) Source is HCV-positive → Refer to care → Test exposed person HCV-negative (known) No further HCV testing needed for source person or exposed person HCV-unknown Option A (preferred) HCV RNA: Neg → STOP Pos → Test exposed person → Refer source person to care Option B Anti-HCV (HCV Ab+): Neg → STOP Pos → Confirm with HCV PCR: PCR Neg → STOP PCR Pos → Test exposed person → Refer source person to care Exposed Person Testing 1 Baseline testing First follow-up (3-6 weeks) 2 Final follow-up (4-6 months) 3 Anti-HCV (HCVAb+) Confirm with HCV RNA if positive. HCV RNA Neg → Follow-up at 4-6 mos. Pos → Refer to care Anti-HCV (HCVAb+) Neg → STOP Pos → Refer to care For detailed explanation, see: Moorman AC, et al. Testing and Clinical Management of Health Care Personnel Potentially Exposed to Hepatitis C Virus — CDC Guidance, United States, 2020. MMWR Recomm Rep 2020;69(No. RR-6):1–8. DOI: https://www.cdc.gov/mmwr/volumes/69/rr/rr6906a1.htm 1 Exposed persons with symptoms of a viral illness compatible with acute HCV at any point up to 6 months post-exposure should be evaluated for acute HCV (anti-HCV, HCV viral load and LFTs). 2 6 weeks coincides with HIV follow-up testing, when indicated. 3 6 months coincides with HBV follow-up testing, when indicated. Follow-Up Testing of the Exposed Person HIV • If SP tests negative for HIV, no follow-up HIV testing is clinically indicated for the EP. • If SP is HIV positive, re-test EP for HIV at 6 weeks and at 3 months. Note: The PEPline recommends final follow-up testing at 3 months. Although the original CDC Guidelines (and many hospital and other protocols) recommend testing to 6 months (or 4 months if testing is performed with the 4th generation Ag/Ab test), delaying follow-up testing beyond 3 months is not necessary with the standard HIV test that is widely used at this time, and can add additional months of anxiety for exposed persons and their families. This PEPline recommendation is consistent with the USPHS non-occupational PEP Guidelines. The USPHS occupational guidelines have not yet been updated to reflect this protocol change. • Extended HIV testing to 12 months is indicated only for HCP who actually acquire HCV infection after exposure to an HCV-HIV co-infected source person. • If SP cannot be tested for HIV or SP is unknown, testing should be as above. • Symptoms of acute HIV should prompt immediate evaluation. HBV (See Exposures to HBV) • If SP tests negative for HBV, no follow-up HBV testing is clinically indicated for the EP. • Follow-up testing is only necessary for exposed persons who do not have hepatitis B immunity (i.e., do not have baseline positive HBsAb after complete vaccine series or do not have knowledge that they responded to the vaccine series). • For those who do not have HBV immunity, see section on HBV. • Symptoms of acute hepatitis should prompt immediate evaluation. HCV (See Exposures to HCV) • If SP is HCV negative, no follow-up testing is clinically indicated for the EP. • See section on HCV for testing protocols. • Symptoms of acute hepatitis should prompt immediate evaluation. Guidance for Exposed Persons What do I do if I am the exposed individual? Exposure to HIV, HBV, and HCV requires immediate evaluation by a medical professional (e.g., emergency room, urgent care, Occupational/Employee Health service, primary care provider). Report your exposure to your supervisor immediately.