What is the workup for a patient with an indeterminate Human Immunodeficiency Virus-1 (HIV-1) antibody test result?

Workup for Indeterminate HIV-1 Antibody Test

Immediately retest the patient with a new specimen and consider HIV-2 testing, while assessing clinical and epidemiologic risk factors to determine if additional virologic testing (HIV RNA PCR) is needed to exclude early acute infection. 1

Initial Assessment and Immediate Actions

Obtain detailed clinical and behavioral history to assess the likelihood of true HIV infection versus false-positive result:

• Document any recent high-risk exposures (unprotected sex, needle sharing, occupational exposure) within the past 6 months 1
• Assess for symptoms of acute retroviral syndrome (fever, lymphadenopathy, rash, pharyngitis) 1
• Identify epidemiologic risk factors for HIV-2 (travel to or origin from West Africa, sexual contact with persons from endemic areas) 1
• In pregnant women, note that indeterminate results occur more frequently than in other populations and may represent false-positives 1, 2

Testing Algorithm for Indeterminate HIV-1 Western Blot

Step 1: Perform HIV-2 EIA testing 1

• If HIV-2 EIA is not repeatedly reactive: The patient should have follow-up HIV-1 antibody testing at 6 months to exclude early seroconversion 1
• If HIV-2 EIA is repeatedly reactive: Send specimen to state public health laboratory for HIV-2 supplemental testing 1
  • If HIV-2 supplemental test is negative: Follow as indeterminate HIV-1 with repeat testing at 6 months 1
  • If HIV-2 supplemental test is positive: Consider patient HIV-infected and manage accordingly; report as presumptive HIV-2 infection 1
  • If HIV-2 supplemental test is indeterminate: Repeat testing at 6 months 1

Step 2: Consider additional virologic testing in high-risk scenarios 1

• HIV RNA PCR (viral load) or p24 antigen testing should be performed for patients with:
  • Behavioral risk factors for recent HIV exposure 1
  • Recent known exposure to HIV 1
  • Clinical symptoms compatible with acute retroviral illness 1
  • Pregnant women requiring urgent management decisions 1
• These tests can detect acute HIV infection during the window period before full antibody development 1

Step 3: Immediate retesting with new specimen 1

• Draw a second blood sample immediately to distinguish between recent seroconversion and laboratory error 1
• Repeat the full testing algorithm (EIA followed by Western blot) on the new specimen 1

Special Considerations for Pregnant Women

Pregnant women with indeterminate results require expedited workup due to implications for perinatal transmission prevention:

• Retest immediately with a new specimen 1
• Consider HIV-1 immunofluorescence assay (IFA) as it is less likely to yield indeterminate results than Western blot 1
• Perform additional virologic tests (viral culture, PCR, or p24 antigen) especially if behavioral risk factors or recent exposure present 1
• Do not make final decisions about antiretroviral therapy or other interventions until HIV status is definitively resolved 1

Follow-Up Protocol for Persistent Indeterminate Results

If results remain indeterminate after initial workup:

• Schedule repeat HIV antibody testing at 6 months from initial test 1
• Counsel patient on strict risk-reduction measures during the 6-month follow-up period 1
• Most indeterminate results in low-risk populations ultimately prove to be false-positives 1
• Consider alternative causes of false-positive results: recent vaccination, pregnancy/parity, autoimmune conditions, or laboratory error 2

Critical Pitfalls to Avoid

Never diagnose or treat HIV infection based on indeterminate results alone:

• Confirmation of HIV infection requires not only laboratory results but also consideration of medical/behavioral history, additional virologic tests when performed, and clinical follow-up 1
• In the absence of recognized epidemiologic risk factors, most indeterminate results in the United States represent false-positives 1
• Specimen-handling errors and laboratory errors are common causes of incorrect results and must always be considered 2
• Do not initiate antiretroviral therapy until infection is definitively confirmed 3

Document all testing clearly and ensure patient understands the meaning of "indeterminate":

• Explain that indeterminate does not mean positive 1
• Clarify that most indeterminate results in low-risk individuals ultimately prove negative 1
• Emphasize the importance of follow-up testing and risk reduction during the evaluation period 1