HIV Test Window Periods
The window period for HIV tests varies by test type: nucleic acid tests (NATs) detect HIV RNA approximately 10-11 days post-exposure, fourth-generation antigen/antibody tests detect infection at 11-18 days, third-generation antibody tests at 22 days, and older antibody-only tests may require up to 3 months for reliable detection. 1, 2, 3
Window Periods by Test Type
Nucleic Acid Tests (NATs/HIV RNA)
- Shortest window period: Approximately 10-11 days post-exposure 1, 3
- Can detect HIV RNA 5-10 days after infection 4
- Detects acute HIV infection approximately 1 week before antigen/antibody tests 1
- Most sensitive test during the early infection period 1
Fourth-Generation Antigen/Antibody Tests
- Window period: Approximately 11-18 days post-exposure 2, 3
- Median window of 18 days (interquartile range 16-24 days) 2
- Detects both HIV p24 antigen and HIV antibodies (IgM and IgG) 1
- Probability of false-negative result drops to 0.01 at 42 days post-exposure 2
- Laboratory-based fourth-generation tests are more sensitive than rapid tests 1
Third-Generation Antibody Tests
- Window period: Approximately 22 days post-exposure 2, 3
- Median window of 22 days (interquartile range 19-25 days) 2
- Detects IgM antibodies in addition to IgG, reducing window compared to older tests 3
- Probability of false-negative result drops to 0.01 at 80 days post-exposure 2
Older Antibody-Only Tests (First/Second Generation)
- Window period: 6-12 weeks (approximately 3 months) post-exposure 3, 5
- Oral fluid-based rapid tests have longer window periods and are less sensitive than blood-based tests 1
- Not recommended for screening in post-exposure prophylaxis contexts 1
Clinical Context: Post-Exposure Prophylaxis (PEP) Testing
Baseline Testing
- Use rapid point-of-care or laboratory-based antigen/antibody test at initial encounter 1
- If rapid test used, also perform laboratory-based Ag/Ab test to increase sensitivity 1
- Consider adding HIV NAT for baseline testing, especially if recent ARV exposure or cabotegravir injection within past year 1
Follow-up Testing Timeline
- First follow-up: 4-6 weeks after PEP initiation (within 2 weeks of completing 28-day course) using both laboratory-based Ag/Ab test and diagnostic NAT 1
- Final follow-up: 12 weeks after PEP initiation (8 weeks after PEP completion) using both laboratory-based Ag/Ab test and diagnostic NAT 1
- This extended timeline accounts for potential ARV suppression of HIV viral load and delayed seroconversion 1
Standard Occupational Exposure Follow-up
- HIV antibody testing should be performed for at least 6 months post-exposure (at 6 weeks, 12 weeks, and 6 months) 1
- Extended follow-up to 12 months may be considered in certain circumstances, though rare delayed seroconversion does not warrant routine extension 1
Important Clinical Considerations
Effect of Antiretroviral Medications
- Critical caveat: ARVs taken as PEP or PrEP can suppress HIV viral load, delay seroconversion, and decrease ability to detect HIV infection 1
- This is why both Ag/Ab tests AND NATs are recommended for follow-up testing after PEP exposure 1
- A negative test at 4-6 weeks does not rule out HIV infection if person was on PEP 1
Test Selection Pitfalls
- Avoid oral fluid-based rapid HIV tests for screening in PEP/exposure contexts—they are less sensitive for acute or recent infection than blood tests 1
- If recommended tests unavailable, use the most sensitive accessible HIV test 1
- Inability to provide HIV NATs should not prevent provision of PEP 1
Indeterminate Results
- If confirmatory testing (Western blot) is negative or indeterminate, follow-up testing should be performed on blood specimen collected 4 weeks after initial reactive HIV test 1
- For high-risk individuals with indeterminate results, repeated serologic testing at 6,12, and 24 weeks may be warranted 1, 6
Timing for Kidney Donor Screening
- All infectious disease testing must be completed within 28 days of planned donation surgery 4
- Testing should be performed 2-4 weeks after return from travel to allow adequate time for infections to become detectable 4
- Minimum of 4 weeks (28 days) after return from travel required to avoid false-negative results during window period 4
Practical Testing Algorithm
For suspected acute exposure:
- Perform fourth-generation Ag/Ab test immediately 1
- Add HIV RNA (NAT) if high suspicion or recent ARV use 1
- If negative but high-risk exposure, repeat at 4-6 weeks with both Ag/Ab and NAT 1
- Final testing at 12 weeks post-exposure with both Ag/Ab and NAT 1
For routine screening without known exposure: