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Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes.

ABSTRACT: Mean duration of recent infection (MDRI) and misclassification of long-term HIV-1 infections, as proportion false recent (PFR), are critical parameters for laboratory-based assays for estimating HIV-1 incidence. Recent review of the data by us and others indicated that MDRI of LAg-Avidity EIA estimated previously required recalibration. We present here results of recalibration efforts using >250 seroconversion panels and multiple statistical methods to ensure accuracy and consensus.A total of 2737 longitudinal specimens collected from 259 seroconverting individuals infected with diverse HIV-1 subtypes were tested with the LAg-Avidity EIA as previously described. Data were analyzed for determination of MDRI at ODn cutoffs of 1.0 to 2.0 using 7 statistical approaches and sub-analyzed by HIV-1 subtypes. In addition, 3740 specimens from individuals with infection >1 year, including 488 from patients with AIDS, were tested for PFR at varying cutoffs.Using different statistical methods, MDRI values ranged from 88-94 days at cutoff ODn = 1.0 to 177-183 days at ODn = 2.0. The MDRI values were similar by different methods suggesting coherence of different approaches. Testing for misclassification among long-term infections indicated that overall PFRs were 0.6% to 2.5% at increasing cutoffs of 1.0 to 2.0, respectively. Balancing the need for a longer MDRI and smaller PFR (<2.0%) suggests that a cutoff ODn = 1.5, corresponding to an MDRI of 130 days should be used for cross-sectional application. The MDRI varied among subtypes from 109 days (subtype A&D) to 152 days (subtype C).Based on the new data and revised analysis, we recommend an ODn cutoff = 1.5 to classify recent and long-term infections, corresponding to an MDRI of 130 days (118-142). Determination of revised parameters for estimation of HIV-1 incidence should facilitate application of the LAg-Avidity EIA for worldwide use.

SUBMITTER: Duong YT

PROVIDER: S-EPMC4339840 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes.

Duong Yen T YT Kassanjee Reshma R Welte Alex A Morgan Meade M De Anindya A Dobbs Trudy T Rottinghaus Erin E Nkengasong John J Curlin Marcel E ME Kittinunvorakoon Chonticha C Raengsakulrach Boonyos B Martin Michael M Choopanya Kachit K Vanichseni Suphak S Jiang Yan Y Qiu Maofeng M Yu Haiying H Hao Yan Y Shah Neha N Le Linh-Vi LV Kim Andrea A AA Nguyen Tuan Anh TA Ampofo William W Parekh Bharat S BS

PloS one 20150224 2

<h4>Background</h4>Mean duration of recent infection (MDRI) and misclassification of long-term HIV-1 infections, as proportion false recent (PFR), are critical parameters for laboratory-based assays for estimating HIV-1 incidence. Recent review of the data by us and others indicated that MDRI of LAg-Avidity EIA estimated previously required recalibration. We present here results of recalibration efforts using >250 seroconversion panels and multiple statistical methods to ensure accuracy and cons ...[more]

PMID: 25710171

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Project description:IntroductionThe need for detection of new and recent HIV infections is essential for surveillance and assessing interventions in controlling the epidemic. HIV recency assays are one way of providing reliable incidence estimates by determining recent versus non-recent infection. The objective of this study was to review the current body of knowledge of the limiting antigen avidity enzyme immunoassay to expand supported applications through an assessment of what is known and the gaps.MethodsA search for peer-reviewed literature in PubMed, Embase, and Web of Science Core Collection was conducted using the search term "human immunodeficiency virus and avidity". Non-peer reviewed published reports from the Population-based HIV Impact Assessment Project were also included. These were limited to literature published in English between January 2010 and August 2021.ResultsThis search resulted in 2080 publications and 14 reports, with 137 peer-reviewed studies and 14 non-peer reviewed reports that met the inclusion criteria, yielding a total of 151 studies for the final review. There were similar findings among studies that compared the performances of assay manufacturers and sample types. Studies that evaluated various assay algorithms and thresholds were heterogeneous, illustrating the need for context-specific test characteristics for classifying recent infections. Most studies estimated subtype-specific test characteristics for HIV subtypes A, B, C, and D. This was further illustrated when looking only at studies that compared HIV incidence estimates from recency assay algorithms and longitudinal cohorts.ConclusionsThese findings suggest that the current body of knowledge provides important information that contributes towards distinguishing recent and non-recent infection and incidence estimation. However, there are knowledge gaps with respect to factors that influence the test characteristics (e.g., HIV-1 subtype, population characteristics, assay algorithms and thresholds). Further studies are needed to estimate and establish context-specific test characteristics that consider these influencing factors to improve and expand the use of this assay for detection of recent HIV infection.

Project description:BackgroundAccurate and practical biologic tools to estimate HIV incidence is crucial to better monitor the epidemic and evaluate the effectiveness of HIV prevention and treatment programs.MethodsWe evaluated two avidity assays to measure recent HIV infection: the Sedia HIV-1 LAg-Avidity EIA (Sedia Biosciences, Portland) and the Centers for Disease Control and Prevention (CDC)-modified Bio-Rad-Avidity assay (Bio-Rad Laboratories, Mississauga, ON). Longitudinal specimens (n = 473) obtained from 123 treatment-naive seroconverted individuals enrolled in the Primary HIV-1 Infection (PHI) cohort of Quebec were used to determine the average time an individual is considered to be recently infected (mean duration of recent infection; MDRI), for the two avidity assays alone and in combination using a nonparametric survival method analysis. A total of 420 specimens from individuals with established HIV infection (90 individuals from the PHI cohort of Quebec and 330 individuals from the Laboratoire de santé publique du Quebec (LSPQ) serobank) were also tested to investigate false recency rate (FRR).ResultsThe CDC-modified Bio-Rad-Avidity gave an estimated MDRI of 234 days (95% CI 220-249) at the avidity index cutoff of 30% while the Sedia-LAg-Avidity assay gave an estimated MDRI of 120 days (95% CI 109-132) at the normalized optical density (ODn) cutoff of 1.5. The FRR among individuals with established HIV infection was 10.2% (7.5%-13.5%) with the CDC-modified Bio-Rad-Avidity assay as compared to 6.0% (3.9%-8.7%) with the Sedia-LAg-Avidity assay. When optimizing a multiassay algorithm (MAA) that includes sequentially the CDC-modified Bio-Rad-Avidity assay then the Sedia-LAg-Avidity assay EIA (avidity index/ODn: 30%/1.7), the MDRI was 136 days (95% CI 123-148) and the FRR, 3.3% (95% CI 1.8-5.6).ConclusionMultiassay algorithms that include the CDC-modified Bio-Rad-Avidity assay and the Sedia-LAg-Avidity assay performed better than each avidity assay alone. Such 2-assay algorithm that starts with the CDC-modified Bio-Rad-Avidity assay followed by the Sedia-LAg-Avidity assay allowed a better classification of HIV-1 infections.

Project description:BackgroundTwo manufacturers, Maxim Biomedical and Sedia Biosciences Corporation, supply CDC-approved versions of the HIV-1 Limiting Antigen Avidity EIA (LAg) for detecting 'recent' HIV infection in cross-sectional incidence estimation. This study assesses and compares the performance of the two assays for incidence surveillance.MethodsWe ran both assays on a panel of 2,500 well-characterized HIV-1-infected specimens. We analysed concordance of assay results, assessed reproducibility using repeat testing and estimated mean durations of recent infection (MDRIs) and false-recent rates (FRRs) for a range of normalized optical density (ODn) thresholds, alone and in combination with viral load thresholds. We defined three hypothetical surveillance scenarios, similar to the Kenyan and South African epidemics, and a concentrated epidemic. These scenarios allowed us to evaluate the precision of incidence estimates obtained by means of various recent infection testing algorithms (RITAs) based on each of the two assays.ResultsThe Maxim assay produced lower ODn values than the Sedia assay on average, largely as a result of higher calibrator readings (mean OD of 0.749 vs. 0.643), with correlation of normalized readings lower (R2 = 0.908 vs. R2 = 0.938). Reproducibility on blinded control specimens was slightly better for Maxim. The MDRI of a Maxim-based algorithm at the 'standard' threshold (ODn ≤1.5 & VL >1,000) was 201 days (95% CI: 180,223) and for Sedia 171 (152,191). The difference Differences in MDRI were estimated at 32.7 (22.9,42.8) and 30.9 days (21.7,40.7) for the two algorithms, respectively. Commensurately, the Maxim algorithm had a higher FRR in treatment-naive subjects (1.7% vs. 1.1%). The two assays produced similar precision of incidence estimates in the three surveillance scenarios.ConclusionsDifferences between the assays can be primarily attributed to the calibrators supplied by the manufacturers. Performance for surveillance was extremely similar, although different thresholds were optimal (i.e. produced the lowest variance of incidence estimates) and at any given ODn threshold, different estimates of MDRI and FRR were obtained. The two assays cannot be treated as interchangeable: assay and algorithm-specific performance characteristic estimates must be used for survey planning and incidence estimation.

Project description:Mean systemic filling pressure (Pms) is a promising parameter in determining intravascular fluid status. Pms derived from venous return curves during inspiratory holds with incremental airway pressures (Pms-Insp) estimates Pms reliably but is labor-intensive. A computerized algorithm to calculate Pms (Pmsa) at the bedside has been proposed. In previous studies Pmsa and Pms-Insp correlated well but with considerable bias. This observational study was performed to validate Pmsa with Pms-Insp in cardiac surgery patients. Cardiac output, right atrial pressure and mean arterial pressure were prospectively recorded to calculate Pmsa using a bedside monitor. Pms-Insp was calculated offline after performing inspiratory holds. Intraclass-correlation coefficient (ICC) and assessment of agreement were used to compare Pmsa with Pms-Insp. Bias, coefficient of variance (COV), precision and limits of agreement (LOA) were calculated. Proportional bias was assessed with linear regression. A high degree of inter-method reliability was found between Pmsa and Pms-Insp (ICC 0.89; 95%CI 0.72-0.96, p = 0.01) in 18 patients. Pmsa and Pms-Insp differed not significantly (11.9 mmHg, IQR 9.8-13.4 vs. 12.7 mmHg, IQR 10.5-14.4, p = 0.38). Bias was -0.502 ± 1.90 mmHg (p = 0.277). COV was 4% with LOA -4.22 - 3.22 mmHg without proportional bias. Conversion coefficient Pmsa ➔ Pms-Insp was 0.94. This assessment of agreement demonstrates that the measures Pms-Insp and the computerized Pmsa-algorithm are interchangeable (bias -0.502 ± 1.90 mmHg with conversion coefficient 0.94). The choice of Pmsa is straightforward, it is non-interventional and available continuously at the bedside in contrast to Pms-Insp which is interventional and calculated off-line. Further studies should be performed to determine the place of Pmsa in the circulatory management of critically ill patients. ( www.clinicaltrials.gov ; TRN NCT04202432, release date 16-12-2019; retrospectively registered).Clinical Trial Registration www.ClinicalTrials.gov , TRN: NCT04202432, initial release date 16-12-2019 (retrospectively registered).

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Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes.

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Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes.

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