What is the recommended initial screening test and treatment regimen for individuals suspected of having Human Immunodeficiency Virus (HIV) using the HIV Antigen/Antibody (Ag/Ab) Combo Electrochemiluminescence Immunoassay (ECLIA)?

HIV Ag/Ab Combo ECLIA Testing

Recommended Initial Screening Approach

The HIV antigen/antibody (Ag/Ab) combination assay (fourth-generation test) is the recommended initial screening test for HIV diagnosis, as endorsed by the CDC, Association of Public Health Laboratories, and IDSA/ASM guidelines. 1, 2

Test Characteristics and Performance

• Fourth-generation HIV Ag/Ab combination assays simultaneously detect HIV-1/2 antibodies and HIV-1 p24 antigen, with sensitivity and specificity both exceeding 99.5% 1, 2

• These assays detect infection 4-7 days after virus becomes detectable by nucleic acid testing (NAT), significantly earlier than third-generation antibody-only tests 1, 2

• The p24 antigen component allows detection during the window period between 14-22 days post-infection, before antibodies become detectable 1

• Laboratory-based Ag/Ab combination assays are superior to rapid point-of-care versions for detecting acute infection, with laboratory tests detecting approximately 65-80% of acute infections that rapid tests miss 3, 4, 5

Diagnostic Algorithm Following Reactive Screening

When the initial Ag/Ab combination assay is reactive, proceed with HIV-1/2 antibody differentiation testing rather than Western blot. 1, 2

If Differentiation Assay is Positive:

• Confirms HIV infection 1
• Proceed with viral load testing and CD4 count determination to guide management 1

If Differentiation Assay is Negative:

• Perform qualitative or quantitative HIV-1 RNA testing (NAT) to rule out acute HIV-1 infection 1, 2
• This scenario suggests either acute infection (antigen-positive but antibody-negative) or a false-positive screening result 1

Critical Testing Considerations

Window Period and Repeat Testing:

• A 10-14 day period exists after infection when no markers are detectable by any test 1
• If initial testing is negative but acute infection is suspected, repeat testing with both laboratory Ag/Ab and NAT at 2-4 weeks is essential 1, 6
• For individuals with recent high-risk exposure (within 72 hours), both laboratory-based Ag/Ab testing and HIV NAT should be performed simultaneously 2

Specimen Requirements:

• Optimal specimens are serum or plasma (EDTA tube) 1
• Plasma should be transported at room temperature within 2 hours 1
• Do not use plasma preparation tubes 1

Special Populations and Pitfalls

Neonates:

• Serologic testing (antibody detection) is unreliable due to maternal antibody persistence up to 15 months 1
• Diagnosis requires HIV-1 RNA quantification (viral load) or proviral DNA testing 1

Patients on PrEP or PEP:

• Antiretroviral medications can suppress viral load and delay antibody formation, reducing test sensitivity 6
• Testing at 12 weeks post-exposure with both Ag/Ab and NAT is recommended for definitive results 6
• Do not delay PEP initiation pending test results 6

Acute Infection Detection Limitations:

• Fourth-generation Ag/Ab assays miss approximately 20-35% of acute infections detectable by NAT, particularly during the exponential viral replication phase 3, 5
• In high-prevalence populations, pooled HIV RNA testing detects an additional 2.4% of infections beyond Ag/Ab combination testing 5
• For populations at very high risk (STI clinics, MSM, injection drug users), consider adding NAT to Ag/Ab screening to maximize acute infection detection 3, 5

Testing Before Treatment Initiation

For All Patients:

• Test for both HIV and hepatitis B virus (HBV) before initiating any antiretroviral therapy 7
• HIV antibody testing must be offered to all HBV-infected patients before starting tenofovir-based regimens 7
• Assess baseline renal function (serum creatinine, estimated creatinine clearance, urine glucose, urine protein) 7

HIV-2 Considerations:

• HIV-2 testing is not routinely recommended unless the patient is from or has partners from endemic areas (West Africa, Angola, Mozambique, Portugal, France) 1
• Consider HIV-2 testing when clinical AIDS symptoms exist with negative HIV-1 testing 1

Confirmatory Testing Algorithm Summary

1. Initial screen: Laboratory-based HIV Ag/Ab combination assay (fourth-generation) 1, 2
2. If reactive: HIV-1/2 antibody differentiation assay 1, 2
3. If differentiation positive: Viral load + CD4 count 1
4. If differentiation negative: HIV-1 NAT to rule out acute infection 1, 2
5. If initial screen negative but high suspicion: Repeat Ag/Ab + NAT at 2-4 weeks 1, 6