What is the recommended follow-up and testing schedule for a patient with high-risk HIV exposure and no post-exposure prophylaxis (PEP)?

HIV Testing Schedule Without Post-Exposure Prophylaxis

For patients with high-risk HIV exposure who do not receive PEP, perform HIV testing at baseline, 6 weeks, 3 months, and 6 months post-exposure using laboratory-based antigen/antibody combination tests, with the most recent CDC guidelines (2025) now recommending the addition of HIV nucleic acid testing (NAT) at key intervals and final testing at 12 weeks when PEP is used—but the traditional 6-month window remains the standard for exposures without PEP. 1

Immediate Actions at Time of Exposure

• Baseline testing (Day 0): Perform a rapid point-of-care HIV test and/or laboratory-based antigen/antibody combination (Ag/Ab) test immediately to establish HIV-negative status before the exposure window begins 1
• Provide immediate wound care: wash wounds and skin with soap and water, flush mucous membranes with water 1
• Test the source patient for HIV antibody using rapid testing when possible to assess exposure risk 1
• Counsel the exposed person about secondary transmission precautions during the follow-up period 1

Follow-Up Testing Timeline Without PEP

The testing schedule differs significantly when PEP is not administered, as antiretroviral medications can suppress viral detection and delay antibody formation 2:

6-Week Testing

• Perform HIV antibody testing at 6 weeks post-exposure 1
• This timepoint captures most early seroconversions in the absence of antiretroviral suppression 1

3-Month Testing

• Perform HIV antibody testing at 3 months post-exposure 1
• This interval provides additional sensitivity for detecting delayed seroconversion 1

6-Month Final Testing

• Perform HIV antibody testing at 6 months post-exposure as the definitive endpoint 1
• This extended window accounts for rare delayed seroconversion and remains the standard when PEP is not used 1
• The 6-month window is based on older third-generation antibody testing but remains recommended in the absence of PEP 2

Critical Distinction: Testing With vs. Without PEP

The 2025 CDC guidelines shorten the testing window to 12 weeks when PEP is used, but this does not apply to exposures without PEP 1:

• When PEP is administered, final testing occurs at 12 weeks using both laboratory Ag/Ab and NAT 1
• When PEP is NOT used, the traditional 6-month window remains appropriate because there is no antiretroviral suppression to account for 1
• Fourth-generation Ag/Ab tests detect HIV approximately 18-45 days post-infection, while NAT can detect infection 10-14 days earlier 2

Enhanced Testing Considerations

While not universally required for non-PEP exposures, consider adding HIV NAT at critical intervals for higher-risk exposures 1:

• At 4-6 weeks: Laboratory Ag/Ab test plus NAT can identify acute infection earlier than antibody testing alone 1
• At 12 weeks: Combined Ag/Ab and NAT testing provides maximum sensitivity 1
• NAT is particularly important when the source has acute HIV infection, as exposed persons with acute infection are highly infectious 2

Counseling and Monitoring Requirements

• Instruct the patient to seek immediate medical evaluation for any acute illness during follow-up, as fever, rash, lymphadenopathy, or flu-like symptoms may indicate acute retroviral syndrome 1, 3
• Advise precautions to prevent secondary transmission during the entire follow-up period, including condom use and avoiding blood/organ donation 1, 3
• Develop a system to encourage exposed persons to return for follow-up testing, as completion rates are often suboptimal 1

Special Circumstances Requiring Extended Follow-Up

In rare cases, extend HIV testing beyond 6 months 2:

• Persons with impaired immune response or inability to develop normal antibody response may require follow-up beyond 6 months 2
• When the source patient has hepatitis C virus (HCV) co-infection, consider extended monitoring 2
• These recommendations are based on older guidelines and are less relevant with modern fourth-generation testing, but remain prudent for immunocompromised patients 2

Common Pitfalls to Avoid

• Do not use oral fluid-based rapid tests for post-exposure follow-up, as they are less sensitive for detecting acute or recent infection than blood-based tests 2
• Do not test discarded needles or syringes for virus contamination—focus testing efforts on the source patient and exposed person 1, 4
• Do not assume a negative test at 6 weeks rules out infection—complete the full 6-month testing schedule when PEP is not used 1
• Do not confuse the 12-week endpoint (for PEP recipients) with the 6-month endpoint (for non-PEP exposures)—these are distinct protocols 1, 2

Concurrent Testing for Other Bloodborne Pathogens

When managing HIV exposure without PEP, also address hepatitis B and C 1, 4:

• Hepatitis B: Assess vaccination status and administer HBIG plus vaccine if indicated within 24 hours of exposure 4
• Hepatitis C: Perform baseline anti-HCV and ALT testing, with follow-up at 4-6 months; HCV RNA at 4-6 weeks if earlier diagnosis desired 1, 4
• No post-exposure prophylaxis exists for hepatitis C 4

Transition to PrEP Consideration

For persons with anticipated repeat or ongoing HIV exposures, consider transitioning to pre-exposure prophylaxis (PrEP) after completing the follow-up testing window 1, 3:

• Perform final HIV testing before initiating PrEP 1, 3
• This strategy is particularly important for individuals who declined PEP but remain at high risk 1, 3