HIV Testing Schedule Using Only Lab-Based Ag/Ab After Exposure
When only laboratory-based antigen/antibody (Ag/Ab) testing is available without nucleic acid testing (NAT), perform testing at baseline, 4-6 weeks post-nPEP initiation, and definitively at 12 weeks post-exposure to rule out HIV infection. 1
Testing Timeline Without NAT
Baseline Testing
- Perform a laboratory-based HIV Ag/Ab test immediately before initiating nPEP to establish HIV-negative status 1
- Do not delay nPEP initiation while awaiting laboratory results 2
- If a rapid point-of-care test is used initially, obtain a laboratory-based Ag/Ab test simultaneously to increase diagnostic sensitivity 1
4-6 Weeks Post-nPEP Initiation
- Perform laboratory-based Ag/Ab testing at this timepoint 1
- This testing can be deferred only if: the person started nPEP within 24 hours of exposure, completed the full 28-day course with good adherence, and is not considering PrEP initiation 1, 2
- A negative test at this time does not rule out HIV infection because antiretrovirals from nPEP may suppress HIV detection for longer than 2 weeks after stopping medications 1
12 Weeks Post-Exposure (Final Testing)
- Perform laboratory-based Ag/Ab testing at 12 weeks post-exposure (8 weeks after completing nPEP) as the definitive test to rule out HIV infection 1, 2, 3
- This timing is based on data regarding antiretroviral washout periods and the window period of HIV tests 1
- Most laboratory-based Ag/Ab tests should detect HIV acquisition from the initial exposure by this timepoint 1
Critical Limitations When NAT Is Unavailable
Reduced Sensitivity for Acute Infection
- Laboratory-based Ag/Ab tests detect HIV approximately 18-45 days post-infection, while NAT can detect infection 10-14 days earlier 3, 4
- Without NAT, you will miss acute HIV infections during the first 2-3 weeks post-exposure 3, 4
- This creates a diagnostic gap where highly infectious individuals may go undetected 1
Impact on Clinical Decision-Making
- The absence of NAT means you cannot identify acute HIV infection as early, which is problematic because persons with acute infection are highly infectious 1
- If someone tests negative on Ag/Ab alone at 4-6 weeks but was actually infected, they may unknowingly transmit HIV or inappropriately start PrEP 2, 5
- Antiretrovirals from nPEP can suppress viral replication and delay antibody formation, making Ag/Ab-only testing even less reliable during the immediate post-nPEP period 2, 3, 5
Common Pitfalls to Avoid
- Never use rapid antibody-only tests (especially oral fluid tests) in the nPEP context, as they are significantly less sensitive than laboratory-based Ag/Ab tests for detecting acute or recent infection 2, 6
- Never conclude HIV testing before 12 weeks post-exposure when using only Ag/Ab testing, as this is the minimum timepoint to account for antiretroviral suppression effects and the Ag/Ab window period 1, 2, 3
- Never assume a negative Ag/Ab test at 4-6 weeks rules out infection in someone who completed nPEP, as residual antiretroviral levels may still be suppressing detectable HIV 1, 2
Practical Considerations
Fourth-generation Ag/Ab combination assays vary in their p24 antigen detection sensitivity, with some performing significantly better than others 6, 7. If NAT is truly unavailable, ensure you are using a high-quality laboratory-based fourth-generation Ag/Ab assay rather than a rapid test 2, 6. Research shows that antibody-based rapid tests miss 46-50% of early infections that fourth-generation laboratory assays detect 6.
The 12-week timepoint remains the definitive window to rule out HIV infection when modern Ag/Ab testing is used without NAT 2, 3. While the CDC strongly recommends including diagnostic NAT at both 4-6 weeks and 12 weeks for optimal sensitivity 1, the reality is that laboratory-based Ag/Ab testing alone at 12 weeks post-exposure should detect the vast majority of infections when accounting for antiretroviral washout 1, 3.