What are the next steps if a patient's OraQuick (HIV rapid test) is reactive and their 4th generation (HIV combination test) is non-reactive?

Management of Discordant HIV Test Results: OraQuick Reactive with Non-reactive 4th Generation Test

When a patient has a reactive OraQuick HIV test but a non-reactive 4th generation test, the next step is to perform a nucleic acid amplification test (NAAT) such as HIV RNA testing to rule out acute HIV infection. 1

Understanding the Discordant Results

• OraQuick is a rapid antibody test that can yield false-positive results, with specificity reported as low as 96.9% in some studies 2
• 4th generation tests detect both HIV antibodies and p24 antigen, allowing for earlier detection of infection than antibody-only tests 1, 3
• This discordant pattern suggests several possibilities:
  • False-positive OraQuick result (most likely scenario) 1, 2
  • Very early HIV infection in the "second diagnostic window" when p24 antigen levels have declined but antibodies aren't yet detectable 4
  • Technical error in one of the tests 3

Recommended Testing Algorithm

1. Perform HIV RNA testing immediately to rule out acute infection 1, 3

   • This is critical as HIV RNA can detect infection before antibody or antigen tests become positive 1

2. If HIV RNA is negative:

   • The OraQuick result is likely a false positive 3, 2
   • Inform the patient that they are likely HIV-negative 1
   • Consider repeat testing in 4 weeks to definitively rule out early infection 1

3. If HIV RNA is positive:

   • Confirm HIV infection and initiate appropriate management 3
   • Order additional tests including CD4 count, viral load quantification, and resistance testing 3

Important Considerations

• False-positive rapid test results are more common than generally appreciated, with one study showing specificity of only 96.9% for OraQuick 2
• Oral fluid tests may have higher false-positive rates than blood-based rapid tests 1, 5
• Patients using PrEP who become infected may take longer to develop reactive antibody tests (191.8 days vs 16.8 days in one study) 5
• Some HIV subtypes may affect the time to antibody test reactivity 5

Special Circumstances

• If the patient has recent high-risk exposure (within 72 hours), consider post-exposure prophylaxis while awaiting definitive results 1
• For patients with ongoing risk factors, PrEP should be considered once HIV infection is definitively ruled out 1
• Rare cases of persistent false-positive results with very high signal-to-cutoff ratios have been reported due to cross-reactivity with other antigens 6

Follow-up Testing

• If initial HIV RNA testing is negative, repeat testing in 4 weeks is recommended to definitively rule out infection 1, 3
• For high-risk individuals, additional serologic testing at 6,12, and 24 weeks may be warranted 1
• Document all test results clearly in the patient's medical record 1

Remember that confirmatory testing is essential before making a definitive diagnosis of HIV infection, and patients should not be counseled about HIV infection based on a reactive screening test alone 1, 3.