Background
Persons with HIV (PWH) who receive antiretroviral treatment (ART) beginning in acute/early stages of infection may fail to develop antibody reactivity or revert to nonreactive levels on serological assays. Seroreactivity after prolonged viral suppression in PWH treated in acute/early stages of infection has not been previously characterized.
Methods
RV254 cohort study identified PWH with recent HIV acquisition in Bangkok using an antigen (Ag)/antibody (Ab) combo-assay, with subsequent testing of nonreactive samples using a nucleic acid test (NAT) and testing of reactive samples with a less sensitive Ab-only assay. Participants with reactive results in the Ag/Ab assay and nonreactive results in the Ab-only assay, and those with nonreactive results in the Ag/Ab assay and reactive results in the NAT were included, categorized according to Fiebig stage, and offered immediate ART with longitudinal follow-up. We obtained plasma samples collected at the latest available timepoint after ART initiation to investigate seroreactivity using the Ortho VITROS HIV Ag/Ab Combo assay, according to Fiebig stage at ART initiation.
Results
345 participants with samples collected between 96 and 480 weeks after ART initiation were included; most samples (64%) were collected at 336 weeks (6.5 years) after ART initiation. At ART onset, 48, 92, 148, and 57 participants were categorized at Fiebig stages 1, 2, 3, and 4, respectively. Overall, 24 participants (7%) had nonreactive results; percentages with nonreactive serology were 38%, 2%, 1%, and 4% with ART initiated at Fiebig stages 1, 2, 3, and 4, respectively (p<0.001). Serology test results are shown in Figure 1. We found progressively lower signal-to-cutoff readouts for participants starting ART at earlier Fiebig stages, with statistical significance comparing Fiebig 1 vs. Fiebig 4 (p<0.001), and Fiebig 2 vs. Fiebig 4 (p=0.001).
Conclusions
ART initiation at acute/early stages after HIV acquisition can suppress antibody reactivity, limiting HIV detectability by licensed diagnostic serologic assays for years following infection. This phenomenon is particularly relevant but not limited to PWH who initiate ART in Fiebig stages 1 and 2, before the emergence of Ab responses. Implications include false negative diagnostic testing in clinical settings, including blood donation screening.
Table or Figure
