PEPline GUIDANCES for Occupational Exposures
The PEPline Guidances are a quick guide to assist in urgent decision-making for occupational exposures to HIV and hepatitis B and C.
Expert consultation can be obtained from Occupational/Employee Health Services, local experts, or the PEPline. The PEPline (888-448-4911) is available daily from 9 am – 2 am EST (6 am – 11 pm PST).
For additional information, please see the CDC Guidelines for Occupational Post-Exposure Prophylaxis. Para obtener esta información en Español por favor oprima aqui.
Abbreviations
- HIV = Human Immunodeficiency Virus
- AIDS = Acquired Immunodeficiency Syndrome
- HBV = Hepatitis B Virus
- HCV = Hepatitis C Virus
- Ab = Antibody
- Ag = Antigen
- SP = Source Patient
- EP = Exposed Person
- PEP = Post-Exposure Prophylaxis (to prevent HIV transmission)
What is considered a potential exposure to HIV, HBV or HCV?
What is the risk of HIV transmission?
What baseline testing should be performed after an exposure?
What follow-up testing should be performed?
What is the time frame for using PEP?
What if I am worried the source may be in the “window period” for HIV.
How do I choose a PEP regimen?
If the source person is HIV infected, do I recommend PEP?
If the source person has an unknown HIV status, do I use PEP?
If the source person is unknown (e.g. sharps box injury), do I use PEP?
How do I manage a human bite with exposure to non-bloody saliva (NBS)?
What are common drug-drug interactions between PEP and the exposed person’s home medications?
What are common side effects of PEP?
How do I manage a pregnant exposed patient?
How do I manage the breastfeeding exposed patient?
How do I manage exposures to HBV?
How do I manage exposures to HCV?
General Information
What is considered a potential exposure to HIV, HBV or HCV?
For transmission of blood borne pathogens (HIV, HBV and HCV) to occur, an exposure must include the following:
- Infectious body fluid:
- Blood, semen, vaginal fluids, amniotic fluids, breast milk, cerebrospinal fluid, pericardial fluid, peritoneal fluid, pleural fluid and synovial flood can transmit HIV, HBV and HCV.
- Note that saliva, vomitus, urine, feces, sweat, tears and respiratory secretions do not transmit HIV (unless visibly bloody). (See section on Non-Bloody Saliva for potential HBV and HCV transmission.)
- A portal of entry (percutaneous, mucous membrane, cutaneous).
If these factors are not present, there is no risk of transmission and further evaluation is not required.
What is the risk of HIV transmission?
|
Route of exposure |
Risk of exposure when source person is HIV positive |
Factors increasing risk |
|
~ 1/300 episodes (0.3%) |
hollow bore needles, visibly bloody devices, and deep injury, device used in an artery/vein |
|
~ 1/1000 episodes (0.09%) |
large volume > small volume |
|
< 1/1000 episodes (0.09%) |
must involve non-intact skin integrity. |
What baseline testing should be performed after an exposure? (If no exposure occurred or SP tests negative, no testing is indicated.)
- Source Person: HIV Ab (rapid HIV Ab testing preferred if accessible), HCV Ab, HBV surface Ag
- If SP’s rapid HIV Ab test is positive, assume this is a true positive and send confirmatory Western Blot testing. Proceed with post-exposure management for an HIV positive SP.
- Exposed Person: HIV Ab, HCV Ab, HBV surface Ag and HBV surface Ab titer
What follow-up testing should be performed?
- Source Person: The SP does not need follow-up testing.
- Exposed Person: Standard follow-up for an EP should include the following:
- HIV
- If SP is HIV positive, check HIV Ab at 6, 12 and 24 weeks. Symptoms of acute HIV should prompt immediate evaluation.
- If SP cannot be tested for HIV or SP is unknown, check HIV Ab at 6, 12, and 24 weeks. Symptoms of acute HIV should prompt immediate evaluation.
- If SP tests negative for HIV, no follow-up HIV testing is recommended for the EP.
- HBV (See section on Management of HBV exposures)
- There is no routine serologic follow-up testing for HBV exposures. However, prophylaxis may be indicated based on the EP’s immunologic status determined by the baseline HBV testing. See Management of HBV Exposures for full management.
- Hepatitis C
- If SP is HCV positive, HCV RNA PCR viral load at 6 weeks and HCV Ab at 12 and 24 weeks. Symptoms of acute hepatitis should prompt immediate evaluation.
- If SP has unknown HCV status, check a HCV Ab at 12 and 24 weeks. Symptoms of acute hepatitis should prompt immediate evaluation.
- If SP is HCV negative, no follow-up testing is recommended for EP.
- HIV
What is the time frame for using PEP?
Efficacy is time sensitive: first dose should be given as soon as possible. Optimal time to start PEP is within hours of exposure, rather than days. 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 to document efficacy.
What if I am worried the source person might be in the “window period” for HIV.
- The “window period” for HIV Ab seroconversion (after infection has occurred but before antibodies develop) can cause patient and provider anxiety around post exposure management. The Guidelines state, “Although concerns have been expressed regarding HIV-negative sources being in the window period for seroconversion, no transmission to health care workers from an exposure source during the window period has been reported in the United States.”
- If the source patient’s HIV test is negative at the time of the exposure, they are generally considered uninfected and HIV PEP is not recommended.
- The “window period” should only be considered when a source patient with risk factors has a high likelihood of being in a window period, particularly if history includes a recent (within 1-2 months) exposure (e.g. sexual, injection drug use, etc) and/or a recent illness consistent with possible acute HIV infection. If acute HIV is highly suspected, PEP should be started while confirmation with the source’s HIV RNA PCR viral load is sent.
PEARLS:
- Do NOT WAIT FOR SP’s BASELINE TEST RESULTS TO PROCEED WITH PEP DECISION unless results of a rapid HIV Ab test on source person will be available within an hour or two.
- PEP can always be stopped when source person testing comes back as negative.
The PEP decision currently is based on exposure type and source patient factors as outlined in the following tables (MMWR Guidelines 2005):
| Recommendations for HIV Post Exposure Prophylaxis after Percutaneous Injury | |||||
| Infection Status of Source | |||||
| Exposure Type | HIV-Positive (HIV-RNA <1500 copies/mL) | HIV-Positive (HIV-RNA >1500 copies/mL) |
Source of unknown HIV status | Unknown sourceØ | HIV-Negative |
| Lower Risk¶ | Basic 2-drug PEP recommended | Expanded 3-drug PEP recommended | Generally, no PEP warranted; however, consider basic 2-drug PEP** for source with HIV risk factors§ | Generally, no PEP warranted; however, consider basic 2-drug PEP** in settings where exposure to HIV-infected persons is likely | No PEP warranted |
| Higher Risk† | Expanded 3-drug PEP recommended | Expanded 3-drug PEP recommended | Generally, no PEP warranted; however, consider basic 2-drug PEP** for source with HIV risk factors§ | Generally, no PEP warranted; however, consider basic 2-drug PEP** in settings where exposure to HIV-infected persons is likely | No PEP warranted |
|
¶ Less severe injury (e.g., solid needle or superficial injury). ** The designation, “consider PEP,” indicates that PEP is optional and should be based on an individualized decision between the exposed person and the treating clinician. § If PEP is offered and taken and the source is later determined to be HIV-negative, PEP should be discontinued. † More severe injury (e.g., large-bore hollow needle, deep puncture, or needle used in patient’s artery or vein). Ø Unknown source (e.g., a needle from a sharps disposal container) Adapted from MMWR 2005;54(No. RR-9). |
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| Recommendations for HIV Post Exposure Prophylaxis after Mucous Membrane and Non-intact Skin∞ Exposures | |||||
| Infection Status of Sources | |||||
| Exposure Type | HIV-Positive (HIV-RNA <1500 copies/mL) | HIV-Positive (HIV-RNA >1500 copies/mL) |
Source of unknown HIV status | Unknown sourceØ | HIV-Negative |
| Small Volume¶ | Consider basic 2-drug PEP | Basic 2-drug PEP recommended | Generally, no PEP warranted. | Generally, no PEP warranted. | No PEP warranted |
| Large Volume† | Basic 2-drug PEP recommended | Expanded 3-drug PEP recommended | Generally, no PEP warranted; however, consider basic 2-drug PEP** for source with HIV risk factors§ | Generally, no PEP warranted; however, consider basic 2-drug PEP** in settings where exposure to HIV-infected persons is likely | No PEP warranted |
|
∞ For skin exposures, follow-up is indicated only if there is evidence of compromised skin integrity (e.g., dermatitis, abrasion, or open wound). Ø Unknown source (e.g. splash from inappropriately disposed blood). ¶ Small volume (i.e., a few drops). ** The designation “consider PEP,” indicates that PEP is optional and should be based on an individualized decision between the exposed person and the treating clinician. § If PEP is offered and taken and the source is later determined to be HIV-negative, PEP should be discontinued. † Large volume (e.g., major blood, amniotic fluid or peritoneal fluid splash, etc.). Adapted from MMWR 2005;54(No. RR-9). |
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How do I choose a PEP regimen?
- There are two general types of PEP regimens to choose from: a Basic regimen and an Expanded regimen.
- If you have a question whether to select a Basic versus Expanded, start with an Expanded regimen option. Seek expert consultation from Occupational/Employee Health or the PEPline the next day.
Basic Regimen
tenofovir + emtricitabine (Truvada®) 1 tab po daily
- OR -
zidovudine + lamivudine (Combivir®) 1 tab po BID
Expanded Regimen
Basic Regimen PLUS lopinavir + ritonavir (Kaletra®) 2 tabs po BID
|
HIV meds |
Adult Dosing |
Toxicity monitoring |
|
Tenofovir@ |
300 mg po daily |
BUN, Creatinine, LFTs |
|
Emtricitabine@ |
200 mg po daily |
Rash |
|
Zidovudine# |
300 mg po BID |
CBC, LFTs |
|
Lamivudine# |
150 mg po BID |
Rash |
|
Lopinavir/ritonavir& (200/50 mg) |
2 tabs po BID |
GI toxicity, expecially diarrhea. LFTs |
@ Truvada = combination tablet of emtricitabine 200mg + tenofovir 300mg
# Combivir = combination tablet with lamivudine 150mg + zidovudine 300mg; generic co-formulation available
& Kaletra = Lopinavir/ritonavir 200mg/50mg formulation
PEARLS:
- Check for drug-drug interactions between the PEP regimen and the exposed person’s current medications.
- Tenofovir+emtricitibine is generally better tolerated and easier to take than zidovudine+lamivudine.
- PEP is given for 28 days and no longer. If source person testing is negative for HIV, PEP can be stopped before 28 days.
- Efavirenz and the efavirenz-containing combination medication, Atripla, are not recommended by the PEPline. Efavirenz is a known teratogen (pregnancy class D), can exacerbate psychiatric conditions, and is associated with rash and neurotoxicities.
If the source person is HIV infected, do I recommend PEP?
- PEP is recommended when an exposure to an HIV positive patient has occurred.
- If the source person is known to be HIV positive, it will be helpful to have information that may affect the recommended PEP regimen. These include:
- What is the SP’s current or most recent viral load?
- Which HIV medications is the SP taking?
- Does the SP have any history of resistance to HIV medications?
- Decisions between basic and expanded regimens are complex. For the purpose of urgent decision- making, start an expanded regimen and seek expert consultation from Occupational/Employee Health or the PEPline the next day.
If the source person has an unknown HIV status, do I recommend PEP?
PEP is generally not warranted in cases of unknown status. However, consider a basic regimen for exposures from a source with HIV risk factors. Some experts even recommend an expanded regimen for serious exposures. If questions exist, seek expert consultation from Occupational/Employee Health or the PEPline the next day.
If the source person is unknown (e.g. sharps box injury), do I use PEP?
PEP is generally not warranted in cases of an unknown source person. However, consider a basic regimen in settings where exposure to HIV-infected persons is likely.
How do I manage my 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 exposure to blood from an unknown SP. A “found needle” is the classic occurrence. No documented cases of HIV transmission from a “found needle” outside of a healthcare setting in the US have occurred. Therefore, the PEPline generally discourages PEP in these cases. Even within health care settings, "found needles" have only been implicated in 3 cases of transmission over the past 2 decades.
How do I manage a human bite with exposure to non-bloody saliva?
- Human bite exposures can result in exposure to both the biter and the bitten person. The bitten sustains a cutaneous exposure to HIV if blood was present in the mouth of the biter before the bite. The biter sustains a mucous membrane exposure to HIV if blood from the bitten person enters the oral cavity of the biter.
- If the saliva is non-bloody, there is no risk to the exposed for HIV. The risk of HBV and HCV transmission from non-bloody saliva is negligible. However, there are a few reports of HBV and possible HCV transmission, so one may consider further evaluation and treatment. (See section on Exposures to HBV and Exposures to HCV)
What are common drug-drug interactions between PEP and the exposed person’s home medications?
- The following drugs should NOT be co-administered with lopinavir/ritonavir (Kaletra); lovastatin, pitavastatin, simvastatin, rifampin, rifapentine, cisapride, pimozide, midazolam, triazolam, dihydroergotamine, ergonovine, ergotamine, methylergonovine, St. John's wort, alfuzosin, salmeterol and sildenafil.
- Other Common medications may have interactions with PEP regimens and require dosing adjustments. Further information can be obtained from the CDC Adult ARV Guidelines (see Table 14 on page 134 of the CDC Adult ARV Guidelines). Contact the PEPline the next day for further consultation regarding evaluation or management of drug-drug interactions.
PEARLS:
Some experts recommend raltegravir in place of lopinavir/ritonavir (Kaletra) as part of an expanded PEP regimen to minimize drug-drug interactions.
What are common side effects of PEP?
Side effects can be a limiting factor in PEP adherence. Side effects are generally self-limited but sometimes can last the duration of the 28-day PEP course. Gastrointestinal side effects (nausea, vomiting, diarrhea) are most common, especially with expanded regimens that include lopinavir/ritonavir. Zidovudine+lamivudine can cause headache, fatigue, insomnia and gastrointestinal upset. Tenofovir+emtricitabine is much better tolerated than zidovudine+lamivudine and is given as once daily dosing. Antiemetic and antidiarrheal medications can be prescribed to help with PEP adherence. If side effects are severe, consider changing to a better tolerated regimen. Toxicities are rare with the current preferred PEP regimens, are generally not life-threatening and are reversible.
How do I manage a pregnant exposed patient?
Pregnancy is not a contraindication to HIV PEP. Zidovudine has been well studied over 20 years and does not appear to be associated with birth defects or significant toxicities in the infant when given for a short time to the mother. There is considerable experience with zidovudine+lamivudine and lopinavir+ritonavir in HIV positive women. The Pregnancy Registry has not shown increased prevalence of birth defects compared with baseline population incidence. The risk, however, is considered higher in the first trimester as compared with later in pregnancy. Most antiretroviral drugs are category B or C. Decision making should weigh the benefits of PEP to the mother and fetus against the unknown effects to the fetus.
How do I manage the breastfeeding exposed person?
Both the HIV virus and antiretroviral medications can be found in breast milk. Some guidelines recommend avoiding breastfeeding for up to 6 months post exposure to prevent potential exposure of the infant to HIV should transmission to the mother occur and/or to avoid potential PEP drug toxicities. Because there are significant benefits from breastfeeding and HIV is rarely transmitted to the exposed person (particularly when PEP is used), the PEPline advises discussing potential risks with the exposed woman and leaving the decision up to the breastfeeding mother. As most transmissions are diagnosed by 6 weeks and almost all transmissions are detected by 3 months, the option to pump and discard breast milk initially and later reinitiate breastfeeding may be a reasonable choice.
How do I manage exposures to HBV?
| Recommendations for Post Exposure Prophylaxis After Exposure to HBV | |||
| Vaccination and antibody response status of exposed person**** | Source HBsAg* positive | Source HBsAg* negative | Source unknown or not available for testing |
| Unvaccinated | HBIG# x 1 and initiate HBV vaccine series immediately | Initiate HBV vaccine series |
Initiate HBV vaccine series If known high risk source, may treat as if source were HBsAg positive |
| Previously vaccinated: | |||
| Known responder** | No treatment | No treatment | No treatment |
| Known nonresponder@@ | HBIG x 1 and initiate revaccination or HBIG x 2 with second dose separated from first by 4 wks*** | No treatment | If known high risk source, treat as if source were HBsAg positive |
| Antibody response unknown |
Test exposed person for HBsAb 1. If adequate**, no treatment necessary 2. If inadequate@@, administer HBIG x 1 and vaccine booster, recheck HBsAb ## titer in 3-4 months. If titer is still inadequate for immunity, complete full second series of vaccinations. |
No treatment |
Test exposed person for HBsAb 1. If adequate**, no treatment necessary 2. If inadequate@@, administer vaccine booster and recheck HBsAb titer in 1-2 months. If titer is still inadequate for immunity, complete full second series of vaccinations. |
|
**** Persons who have previously been infected with HBV are not at risk of re-infection and do not require postexposure prophylaxis * Hepatitis B surface antigen # Hepatitis B immune globulin (dose: 0.06 mL/kg intramuscularly) ## Hepatitis B surface antibody ** A responder is a person with documented adequate levels of HBsAb (> or = 10 mIU/mL) @@ A nonresponder is a person with inadequate levels of HBsAb (<10 mIU/mL) *** The option of giving one dose of HBIG and reinitiating the vaccine series is preferred for nonresponders who have not completed a second 3-dose vaccine series. Two doses of HBIG are preferred for persons who have previously completed a second vaccine series but failed to respond. Adapted from MMWR 2001;50(No. RR-11) |
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How do I manage exposures to HCV?
- The risk of transmission of HCV attributed to needlestick exposure is about 1 in 50 (1.8%) when the source patient is infected. There is no post exposure prophylaxis available for HCV exposures.
- Direct viral testing with HCV RNA PCR viral load at 6 weeks, before HCV Ab seroconversion has occurred, allows for early identification of transmission and subsequent referral for early evaluation and potential HCV treatment. The rate of spontaneous clearance of HCV infection is about 25% in otherwise healthy people. However, early diagnosis and treatment may increase HCV clearance to 90% or greater.
More help?
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, personal physician). Report your exposure to your supervisor immediately.
As the treating clinician, how can I get more help?
- The PEPline Guidances are a quick guide meant to assist in urgent decision-making. Expert consultation can be obtained from Occupational/Employee Health, local experts or the PEPline. The PEPline (888-448-4911) is open daily from 6 am – 11 pm PST (9 am – 2 am EST).
- For additional information, please see the CDC Guidelines for Occupational Post-Exposure Prophylaxis
