Short Communication: Low False Recent Rate of Limiting-Antigen Avidity Assay Among Long-Term Infected Subjects from Guangxi, China

Yu, Li; Laeyendecker, Oliver; Wendel, Sarah K.; Liang, Fuxiong; Liu, Wei; Wang, Xueyan; Wang, Lu; Pang, Xianwu; Fang, Zhong-Liao

doi:10.1089/aid.2015.0097

Cited by 10 publications

(10 citation statements)

References 8 publications

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“…Both the LAg-Avidity EIA and the BED-CEIA PFR were consistent with recent literature. 26,27 The BED-CEIA PFR is the same as was reported from samples collected only from HCMC in southern Vietnam, however, was lower than previously reported in other populations. 27–30 The LAg-Avidity EIA was lower than the AxSYM avidity index assay FRR of 2.7% from the HCMC study.…”

Section: Discussionsupporting

confidence: 76%

Estimating False-Recent Classification for the Limiting-Antigen Avidity EIA and BED-Capture Enzyme Immunoassay in Vietnam: Implications for HIV-1 Incidence Estimates

Shah

Duong

Le³

et al. 2017

AIDS Research and Human Retroviruses

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Laboratory tests that can distinguish recent from long-term HIV infection are used to estimate HIV incidence in a population, but can potentially misclassify a proportion of long-term HIV infections as recent. Correct application of an assay requires determination of the proportion false recents (PFRs) as part of the assay characterization and for calculating HIV incidence in a local population using a HIV incidence assay. From April 2009 to December 2010, blood specimens were collected from HIV-infected individuals attending nine outpatient clinics (OPCs) in Vietnam (four from northern and five from southern Vietnam). Participants were living with HIV for ≥1 year and reported no antiretroviral (ARV) drug treatment. Basic demographic data and clinical information were collected. Specimens were tested with the BED capture enzyme immunoassay (BED-CEIA) and the Limiting-antigen (LAg)-Avidity EIA. PFR was estimated by dividing the number of specimens classified as recent by the total number of specimens; 95% confidence intervals (CI) were calculated. Specimens that tested recent had viral load testing performed. Among 1,813 specimens (north, n = 942 and south, n = 871), the LAg-Avidity EIA PFR was 1.7% (CI: 1.2–2.4) and differed by region [north 2.7% (CI: 1.8–3.9) versus south 0.7% (CI: 0.3–1.5); p = .002]. The BED-CEIA PFR was 2.3% (CI: 1.7–3.0) and varied by region [north 3.4% (CI: 2.4–4.7) versus south 1.0% (CI: 0.5–1.2), p < .001]. Excluding specimens with an undetectable VL, the LAg-Avidity EIA PFR was 1.2% (CI: 0.8–1.9) and the BED-CEIA PFR was 1.7% (CI: 1.2–2.4). The LAg-Avidity EIA PFR was lower than the BED-CEIA PFR. After excluding specimens with an undetectable VL, the PFR for both assays was similar. A low PFR should facilitate the implementation of the LAg-Avidity EIA for cross-sectional incidence estimates in Vietnam.

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Section: Discussionsupporting

confidence: 76%

Estimating False-Recent Classification for the Limiting-Antigen Avidity EIA and BED-Capture Enzyme Immunoassay in Vietnam: Implications for HIV-1 Incidence Estimates

Shah

Duong

Le³

et al. 2017

AIDS Research and Human Retroviruses

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“…Further, we show how the addition of viral load (VL) information can improve accuracy. Research has shown that VL measurements <1,000 copies/mL are associated with false-recent infections and can identify individuals with viral suppression [ 74 , 75 ]. We used the methods of Shaw et al [ 73 ], Janes et al [ 76 ] and Pepe et al [ 77 ] to obtain estimates for the rFRR and its 95% confidence intervals.…”

Section: 0 Methodsmentioning

confidence: 99%

Analysis of Viral Diversity in Relation to the Recency of HIV-1C Infection in Botswana

et al. 2016

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BackgroundCross-sectional, biomarker methods to determine HIV infection recency present a promising and cost-effective alternative to the repeated testing of uninfected individuals. We evaluate a viral-based assay that uses a measure of pairwise distances (PwD) to identify HIV infection recency, and compare its performance with two serologic incidence assays, BED and LAg. In addition, we assess whether combination BED plus PwD or LAg plus PwD screening can improve predictive accuracy by reducing the likelihood of a false-recent result.MethodsThe data comes from 854 time-points and 42 participants enrolled in a primary HIV-1C infection study in Botswana. Time points after treatment initiation or with evidence of multiplicity of infection were excluded from the final analysis. PwD was calculated from quasispecies generated using single genome amplification and sequencing. We evaluated the ability of PwD to correctly classify HIV infection recency within <130, <180 and <360 days post-seroconversion using Receiver Operator Characteristics (ROC) methods. Following a secondary PwD screening, we quantified the reduction in the relative false-recency rate (rFRR) of the BED and LAg assays while maintaining a sensitivity of either 75, 80, 85 or 90%.ResultsThe final analytic sample consisted of 758 time-points from 40 participants. The PwD assay was more accurate in classifying infection recency for the 130 and 180-day cut-offs when compared with the recommended LAg and BED thresholds. A higher AUC statistic confirmed the superior predictive performance of the PwD assay for the three cut-offs. When used for combination screening, the PwD assay reduced the rFRR of the LAg assay by 52% and the BED assay by 57.8% while maintaining a 90% sensitivity for the 130 and 180-day cut-offs respectively.ConclusionPwD can accurately determine HIV infection recency. A secondary PwD screening reduces misclassification and increases the accuracy of serologic-based assays.

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“…This decrease in antibody concentration may also lead to disappearance of p31 antibodies but seems to have little effect on the overall antibody affinity. Indeed, false recent predictions in patients with late stage disease are rare for the LAg-Avidity EIA [ 7 , 19 , 31 ]. In the decision tree, absence of p31 antibodies in patients identified as recently infected only by BED CEIA is considered indicative for the advanced stage of infection.…”

Section: Discussionmentioning

confidence: 99%

Decision tree for accurate infection timing in individuals newly diagnosed with HIV-1 infection

et al. 2017

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BackgroundThere is today no gold standard method to accurately define the time passed since infection at HIV diagnosis. Infection timing and incidence measurement is however essential to better monitor the dynamics of local epidemics and the effect of prevention initiatives.MethodsThree methods for infection timing were evaluated using 237 serial samples from documented seroconversions and 566 cross sectional samples from newly diagnosed patients: identification of antibodies against the HIV p31 protein in INNO-LIA, SediaTM BED CEIA and SediaTM LAg-Avidity EIA. A multi-assay decision tree for infection timing was developed.ResultsClear differences in recency window between BED CEIA, LAg-Avidity EIA and p31 antibody presence were observed with a switch from recent to long term infection a median of 169.5, 108.0 and 64.5 days after collection of the pre-seroconversion sample respectively. BED showed high reliability for identification of long term infections while LAg-Avidity is highly accurate for identification of recent infections. Using BED as initial assay to identify the long term infections and LAg-Avidity as a confirmatory assay for those classified as recent infection by BED, explores the strengths of both while reduces the workload. The short recency window of p31 antibodies allows to discriminate very early from early infections based on this marker. BED recent infection results not confirmed by LAg-Avidity are considered to reflect a period more distant from the infection time. False recency predictions in this group can be minimized by elimination of patients with a CD4 count of less than 100 cells/mm3 or without no p31 antibodies. For 566 cross sectional sample the outcome of the decision tree confirmed the infection timing based on the results of all 3 markers but reduced the overall cost from 13.2 USD to 5.2 USD per sample.ConclusionsA step-wise multi assay decision tree allows accurate timing of the HIV infection at diagnosis at affordable effort and cost and can be an important new tool in studies analyzing the dynamics of local epidemics or the effects of prevention strategies.

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Short Communication: Low False Recent Rate of Limiting-Antigen Avidity Assay Among Long-Term Infected Subjects from Guangxi, China

Cited by 10 publications

References 8 publications

Estimating False-Recent Classification for the Limiting-Antigen Avidity EIA and BED-Capture Enzyme Immunoassay in Vietnam: Implications for HIV-1 Incidence Estimates

Estimating False-Recent Classification for the Limiting-Antigen Avidity EIA and BED-Capture Enzyme Immunoassay in Vietnam: Implications for HIV-1 Incidence Estimates

Analysis of Viral Diversity in Relation to the Recency of HIV-1C Infection in Botswana

Decision tree for accurate infection timing in individuals newly diagnosed with HIV-1 infection

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