The Evolution of STI Testing: A Catalyst for Modern Diagnostic Technologies
From the Laboratory to the Living Room: The Shift in HIV Diagnostics Early HIV diagnostics were laboratory-based enzyme immunoassays (EIAs) that required trained personnel, specialized infrastructure and multi-day turnaround times. These first-generation assays, developed in the mid-1980s, used whole viral lysates to detect IgG antibodies against HIV antigens such as p24, gp41 and gp120. While
which incorporated recombinant proteins and synthetic peptides derived from immunodominant regions of HIV-1 and gp36 of HIV-2. This led to improved sensitivity and reduced false positives. 2 Third-generation “sandwich” EIAs introduced the ability to detect IgM antibodies, shortening the diagnostic window by a further 5.88 days and allowing earlier detection during acute infection. 3 In 2010, the first fourth-generation assay, the Abbott ARCHITECT HIV Ag/Ab Combo, was approved in the United States, combining antibody and p24 antigen detection to enable diagnosis within just weeks of exposure. 4 These assays introduced automated, high-throughput testing
they enabled the first screening of blood supplies, crude antigen preparations led to cross-reactivity and reduced specificity. Furthermore, the window period between infection and detectable anti- bodies remained long, typically 6 to 12 weeks. Advances in assay design led to the development of second-generation assays in the late 1980s,
TIMELINE OF HIV INFECTION
IgG Abs
env pol gag
RNA/p24 Ag
IgM Abs
2ND GENERATION Ab THRESHOLD
3RD GENERATION or 4TH GENERATION Ab THRESHOLD
Figure 1 . Timeline of HIV Infection Following infection, p24 antigen (pink) appears first, followed by IgM (red) and IgG (blue) antibody responses. These markers are detected progressively by second-, third- and fourth-generation assays over the weeks post-infection. Confirmatory tests such as Western blot differentiate IgG responses to gag, pol and env antigens as antibodies mature. Image adapted from: Keating, S. M., et al. (2016). Editorial Commentary: Timing Is Everything: Shortcomings of Current HIV Diagnostics in the Early Treatment Era. Clinical Infectious Diseases , 63 (4), 562-564. https://doi.org/10.1093/cid/ciw369.
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