p24 revisited: a landscape review of antigen detection for early HIV diagnosis

Abstract

: Despite major advances in HIV testing, early detection of infection at the point of care (PoC) remains a key challenge. Although rapid antibody PoC and laboratory-based nucleic acid amplification tests dominate the diagnostics market, the viral capsid protein p24 is recognized as an alternative early virological biomarker of infection. However, the detection of ultra-low levels of p24 at the PoC has proven challenging. Here we review the landscape of p24 diagnostics to identify knowledge gaps and barriers and help shape future research agendas. Five hundred and seventy-four research articles to May 2018 that propose or evaluate diagnostic assays for p24 were identified and reviewed. We give a brief history of diagnostic development, and the utility of p24 as a biomarker in different populations such as infants, the newly infected, those on preexposure prophylaxis and self-testers. We review the performance of commercial p24 assays and consider elements such as immune complex disruption, resource-poor settings, prevalence, and assay antibodies. Emerging and ultrasensitive assays are reviewed and show a number of promising approaches but further translation has been limited. We summarize studies on the health economic benefits of using antigen testing. Finally, we speculate on the future uses of high-performance p24 assays, particularly, if available in self-test format.

Figure 1

Kinetics of HIV markers during acute infection to seroconversion and time-frames of detection by generations of tests. Figure and information adapted from [,–57]. Refer to [58] for further information about disease staging. NAAT: nucleic acid amplification test; EIA: enzyme immunoassay.

Figure 2

Schematic of HIV and p24 structures. (a) Entire virion, (b) capsid fullerene cone superstructure made of hexamers and 12 pentamers, and (c) monomer unit. Sources: [–65].

Figure 3

Prevalence of HIV subtypes worldwide. Source: Los Alamos HIV Sequence Database (http://www.hiv.lanl.gov/). Proportions are calculated from total available sequence data available from each region and may reflect localized biases in sampling.

Figure 4

Schematics of the biosensors in Supplementary Table 5, grouped according to whether novelty is in the structural component of the biosensor, the signal enhancement mechanism, or another/multiple components. For further details and references, refer to Supplementary Table 5.