What is the sensitivity of the INSTI (HIV-1/HIV-2 Antibody and p24 Antigen) test at 21, 30, and 90 days after exposure to Human Immunodeficiency Virus (HIV)?

INSTI HIV Test Sensitivity at 21,30, and 90 Days Post-Exposure

The INSTI HIV-1/HIV-2 antibody test has approximately 69-77% sensitivity at 21 days, significantly improved sensitivity approaching 85-100% at 30 days, and near-complete sensitivity (>99%) by 90 days post-exposure, but it remains inferior to fourth-generation antigen/antibody combination tests for detecting acute infection.

Test Performance During Acute Infection Window

At 21 Days Post-Exposure (3 Weeks)

• The INSTI test detects approximately 69-77% of acute HIV infections at 3 weeks post-exposure 1, 2
• In a study of 49 early seroconverters with reactive third-generation EIA tests, INSTI detected only 34 cases (69.4% sensitivity) 1
• Among acute HIV infection patients, 57.5% had reactive INSTI results when tested during Fiebig stages III-IV 2
• Critical limitation: INSTI will miss 20-30% of infections detectable by laboratory-based third-generation antibody tests at this timepoint 1

At 30 Days Post-Exposure (4-5 Weeks)

• Sensitivity improves substantially to approximately 75-85% at 5 weeks post-infection 2, 3
• The probability of HIV detection reaches 75.5% at 5 weeks from HIV transmission 2
• INSTI becomes reactive approximately 9 days before a positive Western blot, which translates to roughly 3-4 weeks post-infection 3
• However, individuals should not rely on a negative INSTI result to accurately exclude HIV infection within at least 5 weeks of potential exposure 2

At 90 Days Post-Exposure (12 Weeks)

• By 90 days, INSTI achieves near-complete sensitivity of 99.84% for established HIV-1 infection and 100% for HIV-2 3
• All specimens from chronically infected patients with positive immunoblots are detected by INSTI 4
• At this timepoint, INSTI performs equivalently to laboratory-based antibody tests for established infections 3

Critical Clinical Context and Limitations

Why INSTI Misses Early Infections

• INSTI is a third-generation antibody-only test that cannot detect p24 antigen, which appears 14-22 days post-infection before antibodies develop 5, 6
• Third-generation antibody tests like INSTI become positive 7-14 days after detectable virus by nucleic acid testing, translating to 3-4 weeks post-infection 6
• There is an absolute window period of 10-14 days post-exposure where no test can detect HIV 6
• During days 14-28, HIV RNA and p24 antigen are detectable, but antibody tests like INSTI remain negative 6, 7

CDC Recommendations Against INSTI for Post-Exposure Testing

• The CDC explicitly states that oral fluid-based rapid HIV tests (including antibody-only tests like INSTI) are not recommended for HIV screening in post-exposure prophylaxis services because they are less sensitive for acute or recent infection than blood tests 6
• CDC 2025 guidelines recommend laboratory-based fourth-generation antigen/antibody combination tests at baseline, which detect infection 4-7 days after detectable virus (approximately 2-3 weeks post-exposure) 6
• If using a rapid point-of-care test initially, also obtain a laboratory-based Ag/Ab test to increase sensitivity 6

Recommended Testing Algorithm Post-Exposure

Baseline Testing (Immediately After Exposure)

• Use laboratory-based fourth-generation Ag/Ab combination test plus diagnostic NAT (nucleic acid testing) 6
• If INSTI is used for immediate results, it must be supplemented with laboratory-based fourth-generation testing 6

Follow-Up at 4-6 Weeks (28-42 Days)

• Laboratory-based Ag/Ab test plus diagnostic NAT 6
• At this timepoint, INSTI sensitivity is approximately 75-85%, making it inadequate as a standalone test 2, 3

Final Testing at 12 Weeks (90 Days)

• Laboratory-based Ag/Ab test plus diagnostic NAT to definitively rule out infection 6
• INSTI achieves >99% sensitivity at this timepoint but laboratory confirmation remains standard of care 3

Important Caveats for Clinical Practice

Factors That Further Reduce INSTI Sensitivity

• Recent antiretroviral use (PEP or PrEP) can suppress viral load and delay seroconversion, making antibody tests even less reliable 6
• Patients with Fiebig stage II-III infections (early acute infection with negative Western blot) are most likely to be missed 2
• Higher HIV-RNA levels and lower CD4+ counts correlate with non-reactive INSTI results during acute infection 2

When to Bypass INSTI Entirely

• If acute HIV infection is suspected clinically (fever, rash, lymphadenopathy), proceed directly to HIV RNA testing regardless of antibody test results 6, 7
• In post-exposure prophylaxis settings, use fourth-generation laboratory tests from the outset 6
• For individuals with known exposure within the past 5 weeks, INSTI should not be used as the sole diagnostic test 2

Confirmatory Testing Requirements

• Any reactive INSTI result requires confirmation with HIV-1/HIV-2 antibody differentiation assay 5
• If INSTI is used to diagnose acute HIV-1 infection, document subsequent HIV-1 seroconversion by conventional serologic testing 7
• Low-level positive viral loads (<5,000 copies/mL) may represent false positives and require retesting 7