What is post-exposure prophylaxis (PEP) and how is it used to prevent disease after potential exposure to a health risk, such as Human Immunodeficiency Virus (HIV)?

Post-Exposure Prophylaxis (PEP) for HIV Prevention

What is PEP?

Post-exposure prophylaxis (PEP) is a 28-day course of antiretroviral medications that must be initiated within 72 hours (ideally within 24 hours) after potential HIV exposure to prevent infection. 1, 2

PEP works by preventing systemic HIV infection during the brief "window of opportunity" before the virus establishes itself in regional lymph nodes and peripheral blood, which typically occurs within 5 days of exposure. 3

When to Initiate PEP

Timing is Critical

• Start PEP as soon as possible, ideally within 24 hours but no later than 72 hours after exposure. 1, 2
• Do not delay initiation while waiting for HIV test results or source person assessment. 3, 2
• PEP should be treated as an urgent medical concern requiring immediate action. 4

Qualifying Exposures

PEP is indicated for exposures to blood, genital secretions, breast milk, or other potentially infectious body fluids from a person known to be HIV-infected when the exposure represents substantial transmission risk. 3, 1

This includes:

• Occupational needlestick injuries or mucous membrane exposures in healthcare workers 3
• Sexual assault or high-risk sexual exposures 3
• Injection drug use exposures (needle sharing) 3

PEP is NOT recommended when:

• The exposed person is already HIV-positive 1
• The source person is confirmed HIV-negative 1
• Exposure is to bodily fluids that don't pose significant risk (saliva, tears, urine) 1
• More than 72 hours have elapsed since exposure (though clinicians may consider it for serious exposures on a case-by-case basis) 3

Initial Assessment and Testing

Exposed Person Testing

• Perform rapid HIV antibody or rapid antigen-antibody test immediately to rule out pre-existing infection. 3, 2
• Add a laboratory-based fourth-generation antigen/antibody test to increase sensitivity. 2
• Never use oral fluid rapid tests in the PEP context—they are less sensitive for acute infection than blood tests. 2
• Do not delay PEP while awaiting test results; assume the person is HIV-negative and proceed. 3, 2

Source Person Testing

• Test the source person with a fourth-generation HIV antigen-antibody test when possible, as it detects infection several weeks earlier than standard antibody tests. 3, 2
• If the source tests negative and has no signs of acute HIV infection, PEP is not indicated. 3
• Do not test discarded needles or syringes for HIV contamination—this is not recommended. 3, 2

Recommended PEP Regimens

First-Line Regimens for Adults and Adolescents

The CDC recommends three-drug regimens based on integrase inhibitors, which have superior tolerability and adherence compared to older zidovudine-based regimens. 1, 2

Preferred options include:

• Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single-tablet regimen 1, 2
• Dolutegravir (DTG) plus tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) or lamivudine (3TC) 1, 2

Duration

• Complete the full 28-day course of PEP. 1, 2
• Most occupational exposures warrant a three-drug regimen; two-drug regimens are no longer preferred. 3, 4

Regimen Selection Considerations

• Consider the source person's antiretroviral treatment history and potential drug resistance when selecting drugs. 3
• Pregnancy does not preclude optimal PEP regimens and should not be a reason to deny treatment. 3
• Expert consultation is advised for delayed presentations, unknown sources, pregnancy, suspected drug resistance, or significant toxicity. 3

Follow-Up Testing Schedule

The CDC recommends the following testing timeline when using fourth-generation tests: 2

• Baseline: HIV antigen/antibody test plus nucleic acid testing (NAT) 2
• 4-6 weeks: Both laboratory-based HIV Ag/Ab test and diagnostic HIV NAT (except for persons who started PEP within 24 hours and didn't miss doses) 2
• 12 weeks: Both laboratory-based HIV Ag/Ab test and diagnostic HIV NAT—this is considered conclusive 2

Critical caveat: Antiretroviral medications can suppress viral load and delay antibody formation, reducing HIV detection ability. 2

Clinical Monitoring and Counseling

Monitoring for Toxicity

• Evaluate persons taking PEP within 72 hours after starting treatment. 2
• Monitor for drug toxicity for at least 2 weeks. 2
• Common adverse symptoms like nausea and diarrhea can often be managed with antimotility or antiemetic agents without changing the regimen. 3

Counseling Points

Inform exposed persons that: 3

• Knowledge about PEP efficacy is limited, but combination regimens are recommended due to increased potency and concerns about drug resistance 3
• Only zidovudine (ZDV) has been shown to prevent HIV transmission in humans (from the case-control study), but newer agents are more potent 3
• Short-term toxicity is usually limited, but serious adverse events have occurred 3
• Any or all drugs may be declined or stopped by the exposed person 3

Prevention of Secondary Transmission

Advise exposed persons to: 3

• Use precautions to prevent secondary transmission during the 12-week follow-up period 3
• Refrain from donating blood, plasma, organs, tissue, or semen 3
• Consider discontinuing breastfeeding, especially for high-risk exposures 3
• Seek immediate medical evaluation for any acute illness during follow-up (fever, rash, myalgia, fatigue, lymphadenopathy), as this may indicate acute HIV infection 3, 2

Additional Testing and Management

Other Infections

• Test for sexually transmitted infections at baseline. 2
• For hepatitis exposures, test for HBsAg and anti-HCV at baseline. 2
• Administer prophylaxis for other health risks resulting from the exposure when indicated. 3

Risk Reduction

• Provide risk-reduction counseling and intervention services to reduce the risk of recurrent exposures. 3
• For individuals with ongoing HIV risk, consider transitioning directly from PEP to pre-exposure prophylaxis (PrEP) after completing the 28-day course and confirming HIV-negative status. 1, 2

Common Pitfalls to Avoid

• Never delay PEP initiation for any reason—time is critical. 3, 2
• Never use oral fluid rapid tests for PEP follow-up testing. 2
• Never test discarded needles for HIV. 3, 2
• Never deny PEP solely based on pregnancy. 3
• Do not modify patient-care responsibilities of exposed healthcare workers based solely on HIV exposure. 3
• Do not assume low risk without proper assessment—treat exposures as urgent medical concerns. 4