Low sensitivity of the fourth-generation antigen/antibody HIV rapid diagnostic test Determine™ HIV Early Detect for detection of acute HIV infection at the point of care in rural Eswatini: a diagnostic accuracy study

Introduction: The diagnosis of acute HIV Infection (AHI) is challenging in routine settings because it cannot be detected by routine third-generation antibody rapid diagnostic tests (RDTs). The current fourth-generation antibody/antigen RDT, Determine™ HIV Early Detect, has demonstrated high sensitivity in laboratory studies, but field evaluations at the point of care are lacking. We nested a diagnostic accuracy study within a larger study of the burden of sexually transmitted infections in rural Eswatini.

Methods: Adults were enrolled at six routine HIV testing sites (HTS) in the Shiselweni region between June 2022 and April 2023. Determine™ HIV Early Detect was performed by HTS counsellors in parallel with routine HIV testing using a finger-prick blood sample. The reference test was HIV viral load (VL) in the plasma sample, performed on the Xpert platform in the central laboratory. AHI was defined as a negative or discordant HIV test result according to the national serial RDT algorithm and an HIV VL >10,000 copies/ml, or two consecutive HIV VL measurements between the lower limit of detection (40 copies/ml) and 10,000 copies/ml. Established HIV Infection was defined as a positive serial RDT test, and overall HIV Infection as either established HIV Infection or AHI.

Results: One thousand one hundred and sixty-three participants had all test results available; 49 (4.2%) were diagnosed with HIV (39 with established HIV according to the serial RDT algorithm and 10 with AHI). AHI prevalence among participants with HIV negative or discordant routine RDT results was 0.9% (10/1124). The sensitivity of Determine™ HIV Early Detect to detect overall HIV Infection was 83.7% (95% CI 70.3-92.7) and to detect AHI was 20% (95% CI 2.5-55.6%); the specificity was equally high for both 99.8% (95% CI 99.4-100).

Conclusions: The low sensitivity of Determine™ HIV Early Detect to detect AHI when performed at the point of care using finger-prick blood samples in our study contrasts with Other published evaluations from laboratory settings and highlights the importance of field evaluations of the commonly used diagnostic tests.

HIV; HIV infection; acute HIV infection; diagnostic testing; rapid diagnostic test; sub‐Saharan Africa.