Fourth generation HIV rapid diagnostic test: Adequate sensitivity in HIV primary infection settings?

Area of Science:

• Infectious Diseases
• Diagnostic Medicine
• Virology

Background:

• Traditional HIV rapid diagnostic tests (RDTs) have limitations in detecting early HIV-1 infection due to the absence of p24-antigen detection.
• Fourth-generation HIV RDTs, which detect both p24-antigen and HIV-antibodies, aim to shorten the diagnostic window.
• The performance of these fourth-generation tests during primary HIV-1 infection remains under-evaluated.

Purpose of the Study:

• To compare the diagnostic sensitivity of two fourth-generation HIV RDTs: Determine™ Early Detect (Determine) and AQ+ HIV Ag/Ab Combo (AQ+).
• To assess the performance of these tests in detecting HIV-1 during the primary infection stage.

Main Methods:

• Sensitivity analysis of Determine and AQ+ using 162 primary HIV-1 infection samples.
• Primary infection confirmation via Western blot and enzyme immunoassay.
• Correlation of test results with HIV-1 infection dates from medical records.

Main Results:

• Overall sensitivity was high for both assays: 94.4% for Determine and 96.9% for AQ+.
• Pre-seroconversion sensitivity was lower, with AQ+ (81.5%) outperforming Determine (66.7%).
• Both assays showed 100% sensitivity after three weeks post-infection, but limited sensitivity between two and three weeks.

Conclusions:

• Fourth-generation HIV RDTs are valuable tools for diagnosing suspected primary HIV-1 infections.
• Clinical use requires caution during the initial three weeks following infection due to potential false negatives.
• AQ+ demonstrated superior sensitivity in the pre-seroconversion period compared to Determine.