Short Communication: The Impact of Viral Suppression and Viral Breakthrough on Limited-Antigen Avidity Assay Results in Individuals with Clade B HIV Infection

Abstract

We analyzed the impact of HIV viral load on the performance of a limiting antigen avidity enzyme immunoassay (LAg-Avidity assay) and determined if this assay could be used to identify viral breakthrough. Three groups of samples were tested: (1) 18 individuals (30 samples) previously identified as elite suppressors; (2) 18 individuals (72 samples) who were continually suppressed on antiretroviral treatment (ART) with 1 sample before and 2-6 samples (one/year) after ART initiation; and (3) 20 individuals (179 samples) on ART who had evidence of viral breakthrough (>400 copies/ml) with subsequent viral suppression. Elite suppressors had the lowest LAg-Avidity assay values. Among those who were continually suppressed on ART, 83% (15/18) had LAg-Avidity assay values that decreased over time. Although the LAg-Avidity assay on a single sample cannot identify when a viral breakthrough occurs, paired longitudinal samples could identify viral breakthrough (sensitivity: 65%, specificity: 84%).

HIV Antibody Level as a Marker of HIV Persistence and Low-Level Viral Replication

“…The ability to identify the degrees of cumulative HIV replication or antigen expression taking place in reservoirs of ART recipients (or even untreated individuals) could be particularly important for ongoing research aiming to enhance intrinsic control of the HIV reservoir. Analysis of serial antibody levels could be used to assess pre-intervention control in patients receiving ART or to monitor changes in low-level viral burdens that may occur during viral breakthrough, as has been shown in other studies [12,14], or during treatment interruption. A validated measure of tight viral control could be useful in identifying patients who were more or less likely to have low reservoirs during ART.…”

“…Given the established association between antigenic burden and antibody production that has been noted in HTLV-1 and HIV [12][13][14][15][16][17][18][19], we hypothesized that the total size of the reservoir is directly associated with the degree of systemic antigen exposure. We also hypothesized that antigen expression contributes to the level of antibody production and avidity and that antibody levels can hence be used as a surrogate marker of the HIV reservoir during ART [20].…”

Evaluation of multi-assay algorithms for identifying individuals with recent HIV infection: HPTN 071 (PopART)

“…Viral suppression can also impact the accuracy of individual serologic incidence assays by altering the antibody response to HIV infection [ 27 – 30 ]. Individuals who are virally suppressed on ART have low levels of circulating virus.…”

Comprehensive Profiling of HIV Antibody Evolution

“…Generalized antibody responses to HIV infection, such as antibody titer and avidity, tend to plateau approximately 1 year after HIV infection ( Busch et al, 2010 ). These characteristics of the antibody response are impacted by a variety of factors, including natural and drug-induced viral suppression ( Koenig et al, 2013 ; Wendel et al, 2017 ; Kassanjee et al, 2014 ), disease progression ( Laeyendecker et al, 2012b ), and HIV subtype ( Longosz et al, 2014 , 2015 ). Previous studies evaluating the banding pattern in western blots demonstrate that HIV antibody specificity evolves early in infection ( Fiebig et al, 2003 ).…”