Post-Exposure Prophylaxis (PEP) Indications for Healthcare Providers

PEP is indicated for healthcare workers following percutaneous injury (needlestick, cut) or mucous membrane/non-intact skin exposure to blood or potentially infectious body fluids from a source known or suspected to be HIV-positive. 1

Exposure Types Requiring Clinical Evaluation for PEP

High-Risk Exposures (PEP Recommended)

Percutaneous injuries (needlestick or cut with sharp object) involving blood, visibly bloody fluids, or other potentially infectious materials (semen, vaginal secretions, cerebrospinal, synovial, pleural, peritoneal, pericardial, or amniotic fluid) from HIV-positive or high-risk unknown sources 1, 2
Mucous membrane exposure (splash to eyes, nose, mouth) to the same body fluids listed above 1, 3
Non-intact skin exposure (dermatitis, abrasion, open wound) with direct contact to blood or potentially infectious fluids, particularly if prolonged or involving large surface area 1, 3
Concentrated HIV exposure in research laboratory or production facility settings 1

Lower-Risk Exposures (Case-by-Case Evaluation)

Human bites resulting in blood exposure to either the bite recipient or person who inflicted the bite (though HIV transmission by this route is rare) 1
Intact skin exposure with prolonged contact or large surface area involvement 1
Unknown source exposures in high HIV prevalence settings (e.g., geographic areas with prevalent injection drug use, AIDS units) 1, 2

Exposures NOT Requiring PEP

Contact with feces, nasal secretions, saliva, sputum, sweat, tears, urine, or vomitus unless visibly bloody 3
Intact skin exposure to small amounts of blood without prolonged contact 1, 3
Exposure to source confirmed HIV-negative with no recent high-risk behaviors 1

Source Patient Evaluation Algorithm

Immediate Actions

Test the source patient for HIV as rapidly as possible using FDA-approved rapid HIV antibody test or enzyme immunoassay (EIA) within 24-48 hours 1
Do not delay PEP initiation while awaiting source testing results if exposure is high-risk 1, 2
Obtain informed consent from source patient; if unconscious, follow state/local laws for testing 1

Source Patient Risk Stratification

Known HIV-positive source: Gather information on disease stage (asymptomatic vs AIDS), CD4+ count, viral load, current/previous antiretroviral therapy, and treatment response to guide PEP regimen selection 1
Unknown HIV status: Evaluate for clinical symptoms (acute HIV syndrome, immunodeficiency), laboratory data (prior HIV tests, CD4+ counts), and risk behaviors (injection drug use, multiple sexual partners, blood products pre-1985) 1
HIV-negative source with recent high-risk behaviors (within 3-6 months): Consider baseline and follow-up testing of healthcare worker at 3 and/or 6 months, though utility is unclear 1

PEP Initiation and Timing

PEP must be started as soon as possible, ideally within 1-2 hours, but no later than 72 hours after exposure. 1, 2, 4 Animal studies demonstrate efficacy is time-dependent, with effectiveness decreasing significantly after 24-36 hours. 2

Critical Timing Pitfalls to Avoid

Never delay the first PEP dose while awaiting HIV testing results of either the exposed healthcare worker or source patient 2
Do not wait beyond 72 hours to initiate PEP, as effectiveness drops dramatically 2
PEP regimen can be modified after initiation based on source patient information that becomes available later 1

Recommended PEP Regimens

Standard Three-Drug Regimen (Preferred for Most Exposures)

Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as single-tablet regimen once daily for 28 days 2

Alternative: Dolutegravir (DTG) 50mg once daily PLUS emtricitabine/tenofovir alafenamide (FTC/TAF) 200mg/25mg once daily for 28 days 2

Two-Drug Regimen (Historical, Less Commonly Used)

Zidovudine (ZDV) plus lamivudine (3TC) for lower-risk exposures, though current guidelines favor three-drug regimens for adequate coverage 1, 2

Regimen Selection Factors

Increased transmission risk exposures (deep injury, visible blood on device, hollow-bore needle from vein/artery, source with high viral load or AIDS): Use three-drug regimen with protease inhibitor or integrase inhibitor 1, 2
Known or suspected antiretroviral resistance in source patient: Add third drug (protease inhibitor such as indinavir or nelfinavir historically, or integrase inhibitor currently) 1
Renal impairment: Use tenofovir alafenamide (TAF) instead of tenofovir disoproxil fumarate (TDF) for better renal safety 2

Baseline and Follow-Up Testing Protocol

Baseline Testing (Before Starting PEP)

HIV antigen/antibody combination test 2
Hepatitis B surface antigen (HBsAg) and antibody status 5, 6, 7
Hepatitis C antibody (anti-HCV) 5, 6, 7
Baseline renal function (creatinine) before tenofovir-based regimens 2
Pregnancy test for women of childbearing age with unknown pregnancy status 1
Baseline liver enzymes (ALT) 3

Follow-Up Testing Schedule

HIV testing: 4-6 weeks, 12 weeks (3 months), and potentially 6 months post-exposure 1, 2, 5
Hepatitis C: Anti-HCV and ALT at 4-6 months post-exposure 3, 5
Hepatitis B: Follow vaccination/HBIG protocol as indicated 5

Concurrent Bloodborne Pathogen Management

Hepatitis B

Unvaccinated healthcare worker with HBsAg-positive source: Administer hepatitis B immune globulin (HBIG) within 24 hours (up to 7 days acceptable) AND initiate hepatitis B vaccine series 3, 5, 6, 7
Vaccinated healthcare worker with unknown antibody response: Check anti-HBs; if inadequate, give HBIG and vaccine booster 3

Hepatitis C

No post-exposure prophylaxis available 3, 6, 7
Perform baseline anti-HCV and ALT, repeat at 4-6 months 3
If acute hepatitis C develops, interferon-alpha monotherapy can prevent chronification in most patients 6, 7

Syphilis (Rare Consideration)

Risk of transmission via needlestick is substantially lower than other bloodborne pathogens 8
Consider prophylactic benzathine penicillin G 2.4 million units IM single dose for high-risk exposures (source with known early syphilis) 8
Alternative for penicillin allergy: Doxycycline 100mg orally twice daily for 14 days 8
Serial testing at 0,4-6 weeks, and 3 months 8

Monitoring During PEP

Toxicity Monitoring

Complete blood count and renal/hepatic function tests at baseline and 2 weeks after starting PEP 1
If protease inhibitor included: Monitor for crystalluria, hematuria, hemolytic anemia, hepatitis 1
Symptoms requiring immediate evaluation: Back or abdominal pain, pain on urination, blood in urine, hyperglycemia symptoms (increased thirst/frequent urination) 1

Managing Side Effects to Promote Adherence

Nausea and diarrhea are common; prescribe antimotility and antiemetic agents without changing regimen 1
Consider modifying dose interval (lower dose more frequently) per manufacturer recommendations 1
Complete the full 28-day course—this is essential for efficacy 2, 4

Counseling and Secondary Transmission Prevention

During Follow-Up Period (Especially First 6-12 Weeks)

Sexual abstinence or condom use to prevent sexual transmission 1
Avoid pregnancy during follow-up period 1
Refrain from donating blood, plasma, organs, tissue, or semen 1
Breastfeeding: Consider discontinuation, especially after high-risk exposures; temporarily discontinue while taking PEP to avoid infant exposure to antiretrovirals 1

For Pregnant Healthcare Workers

Discuss potential benefits and risks to both woman and fetus before initiating PEP 2
Data on antiretroviral toxicity in pregnancy are limited for ZDV and unknown for other agents 1

Acute Illness During Follow-Up

Seek immediate medical evaluation for fever, rash, myalgia, fatigue, malaise, or lymphadenopathy (may indicate acute HIV infection or drug reaction) 1

Special Circumstances

Unknown Source Exposures

Assess epidemiologically: HIV prevalence in the population/institution, type of exposure (blood-filled hollow needle vs injection needle), geographic area risk factors 1
Do not test needles or sharp instruments for HIV—reliability and interpretation are unknown 1
Treat as high-risk and initiate three-drug PEP if epidemiologic assessment suggests significant risk 2

Healthcare Worker Patient-Care Responsibilities

No need to modify patient-care duties based solely on HIV exposure 1
If HIV seroconversion detected, evaluate per published recommendations for HIV-infected healthcare workers 1

Key Clinical Pitfalls

Delaying PEP beyond 72 hours—effectiveness drops dramatically 2
Waiting for source HIV testing before starting first dose—initiate immediately for high-risk exposures 2
Using two-drug regimen for unknown source status—current guidelines favor three-drug regimens 2
Stopping PEP prematurely—full 28-day course is essential 2
Not considering potential toxicity—PEP is not justified for negligible-risk exposures 1
Failing to provide psychological support—emotional impact is substantial despite low transmission risk 1

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