What is the recommended initial blood test for HIV screening in a patient?

Initial Blood Test for HIV Screening

A fourth-generation HIV antigen/antibody combination assay is the recommended initial blood test for HIV screening. 1

Why Fourth-Generation Testing is Preferred

The fourth-generation assay simultaneously detects both HIV p24 antigen and HIV antibodies (IgM and IgG), allowing for significantly earlier detection of infection compared to older antibody-only tests. 1 This dual detection capability reduces the diagnostic window period to approximately 18-45 days post-infection, detecting HIV infection 4-7 days after the virus becomes detectable by nucleic acid amplification testing (NAAT). 1

Key performance characteristics:

• Sensitivity and specificity both exceed 99.5% 1
• Detects infection approximately 4-7 days earlier than third-generation antibody-only tests 1, 2
• Can identify acute HIV infection before antibodies fully develop 2, 3

The Complete Testing Algorithm

Step 1: Initial Screening

Perform a fourth-generation HIV antigen/antibody combination assay as the first test. 1 This can be either:

• Laboratory-based fourth-generation test (preferred for highest sensitivity) 4
• Rapid point-of-care antigen/antibody test (acceptable, but should be supplemented with laboratory-based testing) 4

Important caveat: Oral fluid-based rapid HIV tests are less sensitive for acute or recent infection and should not be used in post-exposure prophylaxis contexts. 4

Step 2: If Initial Test is Reactive

When the fourth-generation screening test is repeatedly reactive, perform an HIV-1/HIV-2 antibody differentiation immunoassay to distinguish between HIV-1 and HIV-2 infections. 1, 5

Step 3: If Differentiation Assay is Negative or Indeterminate

If the differentiation assay is negative despite a reactive screening test, perform nucleic acid amplification testing (NAAT) to rule out acute HIV-1 infection. 1, 5 This scenario suggests possible acute infection where antigen is present but antibodies have not yet developed.

Special Circumstances Requiring Modified Approach

Recent High-Risk Exposure (Within 72 Hours)

For patients presenting within 72 hours of potential exposure (particularly in post-exposure prophylaxis evaluation contexts):

• Perform rapid HIV antibody testing immediately 1
• Also obtain both a laboratory-based antigen/antibody test AND an HIV NAAT 1, 4
• Do not delay post-exposure prophylaxis pending test results 6

Patients on Antiretroviral Therapy

For individuals currently taking or recently exposed to antiretrovirals (PrEP, PEP, or cabotegravir injection within the past year):

• Perform both laboratory-based antigen/antibody test AND diagnostic NAAT 4
• This dual approach is necessary because antiretrovirals may suppress viral load, potentially causing false-negative results on standard testing 4

Infants Born to HIV-Positive Mothers

For infants under 15-18 months of age:

• Do NOT use standard antibody testing, as maternal antibodies cross the placenta and will cause false-positive results 5
• Definitive diagnosis requires laboratory evidence of HIV in blood or tissues by culture, nucleic acid testing, or antigen detection 1, 5

HIV-2 Considerations

HIV-2 testing should be considered when:

• The patient is from or has sex partners from West Africa or other HIV-2 endemic regions 6, 5
• Clinical evidence suggests HIV disease but HIV-1 tests are negative 6, 5
• HIV-1 Western blot shows unusual indeterminate pattern (gag plus pol bands without env bands) 6

Critical Pitfalls to Avoid

Never diagnose HIV based on screening test alone. All reactive screening tests must be confirmed with additional testing before making a definitive diagnosis. 5 False-positive screening results can occur and have devastating psychological and social consequences.

Understand the window period. Even fourth-generation tests cannot definitively rule out infection that occurred less than 6 months before testing, as rare cases of delayed seroconversion have been documented. 4, 5 At least 95% of infected individuals will have detectable antibodies within 6 months. 4

For suspected acute infection (within the first few weeks after exposure): Standard antibody testing may be negative even when infection is present. 4 In these cases, NAAT should be performed rather than relying solely on antibody or antigen/antibody combination tests, as NAAT can detect HIV 10-14 days after exposure. 4

Follow-Up Testing Timeline

For patients with initial negative results but ongoing risk:

• High-risk individuals should be tested at least annually 1
• Very high-risk individuals should be tested every 3 months 1
• After post-exposure prophylaxis: test at 4-6 weeks and again at 12 weeks after PEP initiation 4