Browsing by Author "Santos, Breno R."

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    Comparison of cross-sectional HIV incidence assay results from dried blood spots and plasma
    (Public Library of Science, 2017-02-23) Schlusser, Katherine E.; Pilcher, Christopher; Kallas, Esper G.; Santos, Breno R.; Deeks, Steven G.; Facente, Shelley; Keating, Sheila M.; Busch, Michael P.; Murphy, Gary; Welte, Alex; Quinn, Thomas; Eshleman, Susan H.; Laeyendecker, Oliver
    Background: Assays have been developed for cross-sectional HIV incidence estimation using plasma samples. Large scale surveillance programs are planned using dried blood spot (DBS) specimens for incidence assessment. However, limited information exists on the performance of HIV cross-sectional incidence assays using DBS. Methods: The assays evaluated were: Maxim HIV-1 Limiting Antigen Avidity EIA (LAg-Avidity), Sedia HIV-1 BED-Capture EIA (BED-CEIA), and CDC modified BioRad HIV-1/2 Plus O Avidity-based Assay (CDC-BioRad Avidity) using pre-determined cutoff values. 100 matched HIV-1 positive plasma and DBS samples, with known duration of infection, from the Consortium for the Evaluation and Performance of HIV Incidence Assays repository were tested. All assays were run in duplicate. To examine the degree of variability within and between results for each sample type, both categorical and continuous results were analyzed. Associations were assessed with Bland Altman, R2 values and Cohen’s kappa coefficient (ĸ). Results: Intra-assay variability using the same sample type was similar for all assays (R2 0.96 to 1.00). The R2 values comparing DBS and plasma results for LAg-Avidity, BED-CEIA, and CDC-BioRad Avidity were 0.96, 0.94, and 0.84, respectively. The concordance and ĸ values between DBS and plasma for all three assays were >87% and >0.64, respectively. The Bland-Altman analysis showed significant differences between plasma and DBS samples. For all three assays, a higher number of samples were classified as recent infections using DBS samples. Conclusions: DBS and plasma sample results were highly correlated. However, when compared to plasma, each assay performed somewhat differently in DBS at the lower and higher ends of the dynamic range. DBS samples were more likely to be classified as recently infected by all three assays, which may lead to overestimation of incidence in surveys using performance criteria derived for plasma samples.
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    Computational analysis of antibody dynamics identifies recent HIV-1 infection
    (American Society for Clinical Investigation, 2018) Seaton, Kelly E.; Vandergrift, Nathan A.; Deal, Aaron W.; Rountree, Wes; Bainbridge, John; Grebe, Eduard; Anderson, David A.; Sawant, Sheetal; Shen, Xiaoying; Yates, Nicole L.; Denny, Thomas N.; Liao, Hua-Xin; Haynes, Barton F.; Robb, Merlin L.; Parkin, Neil; Santos, Breno R.; Garrett, Nigel; Price, Matthew A.; Naniche, Denise; Duerr, Ann C.; The CEPHIA group; Keating, Sheila; Hampton, Dylan; Facente, Shelley; Marson, Kara; Welte, Alex; Pilcher, Christopher D.; Cohen, Myron S.; Tomaras, Georgia D.
    Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention strategies. Current assays are limited by high false recent rates (FRRs) in certain populations and a short mean duration of recent infection (MDRI). Dynamic early HIV-1 antibody response kinetics were harnessed to identify biomarkers for improved incidence assays. We conducted retrospective analyses on circulating antibodies from known recent and longstanding infections and evaluated binding and avidity measurements of Env and non-Env antigens and multiple antibody forms (i.e., IgG, IgA, IgG3, IgG4, dIgA, and IgM) in a diverse panel of 164 HIV-1–infected participants (clades A, B, C). Discriminant function analysis identified an optimal set of measurements that were subsequently evaluated in a 324-specimen blinded biomarker validation panel. These biomarkers included clade C gp140 IgG3, transmitted/founder clade C gp140 IgG4 avidity, clade B gp140 IgG4 avidity, and gp41 immunodominant region IgG avidity. MDRI was estimated at 215 day or alternatively, 267 days. FRRs in untreated and treated subjects were 5.0% and 3.6%, respectively. Thus, computational analysis of dynamic HIV-1 antibody isotype and antigen interactions during infection enabled design of a promising HIV-1 recency assay for improved cross-sectional incidence estimation.