Development of a proficiency testing program for the HIV-1 BED incidence assay in China.
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ABSTRACT:
SUBMITTER: Yan H
PROVIDER: S-EPMC3968539 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:A number of antibody biomarkers have been developed to distinguish between recent and established Human Immunodeficiency Virus (HIV) infection and used for HIV incidence estimation from cross-sectional specimens. In general, a cut-off value is specified, and estimates of the following parameters are needed: (i) the mean time interval .w/ between seroconversion and reaching that cut-off; (ii) the probability of correctly identifying individuals who became infected in the last w years (sensitivity); and (iii) the probability of correctly identifying individuals who have been infected for more than w years (specificity). We develop two statistical methods to study the distribution of a biomarker and derive a formula for estimating HIV incidence from a cross-sectional survey. Both methods allow handling interval censored data and basically consist of using a generalized mixture model to model the growth of the biomarker as a function of time since infection. The first uses data from all followed-up individuals and allows incidence estimation in the cohort, whereas the second only uses data from seroconverters. We illustrate our methods using repeated measures of the IgG capture BED enzyme immunoassay. Estimates of calibration parameters, that is, mean window period, mean recency period, sensitivity, and specificities obtained from both models are comparable. The formula derived for incidence estimation gives the maximum likelihood estimate of incidence which, for a given window period, depends only on sensitivity and specificity. The optimal choice of the window period is discussed. Numerical simulations suggest that data from seroconverters can provide reasonable estimates of the calibration parameters.
| S-EPMC4104586 | biostudies-literature
Project description:Laboratory assays for identifying recent HIV-1 infections are widely used for estimating incidence in cross-sectional population-level surveys in global HIV-1surveillance. Adequate assay and laboratory performance are required to ensure accurate incidence estimates. The NIAID-supported External Quality Assurance Program Oversight Laboratory (EQAPOL) established a proficiency testing program for the most widely-used incidence assay, the HIV-1 Limiting Antigen Avidity EIA (LAg), with US Centers for Disease Control and Prevention (CDC)-approved kits manufactured by Sedia Biosciences Corporation and Maxim Biomedical. The objective of this program is to monitor the performance of participating laboratories. Four rounds of blinded external proficiency (EP) panels were distributed to up to twenty testing sites (7 North American, 5 African, 4 Asian, 2 South American and 2 European). These panels consisted of ten plasma samples: three blinded well-characterized HIV-1-seropositive samples that were included as replicates and an HIV-negative control. The seropositive samples spanned the dynamic range of the assay and are categorized as either recent or long-term infection. Participating sites performed the assay according to manufacturers' instructions and completed an online survey to gather information on kit manufacturer, lot of kit used, laboratory procedures and the experience of technicians. On average, fifteen sites participated in each round of testing, with an average of four sites testing with only the Maxim assay, seven testing with only the Sedia assay and five sites utilizing both assays. Overall, the Sedia and Maxim assays yielded similar infection status categorization across the laboratories; however, for most of the nine HIV+ samples tested, there were significant differences in the optical density readouts, ODn (N = 8) and OD (N = 7), between LAg kit manufacturers (p < 0.05 based on mixed effects models. The EQAPOL LAg program is important for monitoring laboratory performance as well as detecting variations between manufacturers of HIV-1incidence assays.
| S-EPMC6746377 | biostudies-literature
Project description:BackgroundThe objectives of this study were to determine the capacity of BED incidence testing to a) estimate the effect of a HIV prevention intervention and b) provide adequate statistical power, when used among young people from sub-Saharan African settings with high HIV incidence rates.MethodsFirstly, after having elaborated plausible scenarios based on empirical data and the characteristics of the BED HIV-1 Capture EIA (BED) assay, we conducted statistical calculations to determine the BED theoretical power and HIV incidence rate ratio (IRR) associated with an intervention when using BED incidence testing. Secondly, we simulated a cross-sectional study conducted in a population among whom an HIV intervention was rolled out. Simulated data were analyzed using a log-linear Poisson model to recalculate the IRR and its confidence interval, and estimate the BED practical power. Calculations were conducted with and without corrections for misclassifications.ResultsCalculations showed that BED incidence testing can yield a BED theoretical power of 75% or more of the power that can be obtained in a classical cohort study conducted over a duration equal to the BED window period. Statistical analyses using simulated populations showed that the effect of a prevention intervention can be estimated with precision using classical statistical analysis of BED incidence testing data, even with an imprecise knowledge of the characteristics of the BED assay. The BED practical power was lower but of the same magnitude as the BED theoretical power.ConclusionsBED incidence testing can be applied to reasonably small samples to achieve good statistical power when used among young people to estimate IRR.
| S-EPMC3154202 | biostudies-literature
Project description:BACKGROUND: Performance of the BED assay in estimating HIV-1 incidence has previously been evaluated by using longitudinal specimens from persons with incident HIV infections, but questions remain about its accuracy. We sought to assess its performance in three longitudinal cohorts from Thailand where HIV-1 CRF01_AE and subtype B' dominate the epidemic. DESIGN: BED testing was conducted in two longitudinal cohorts with only incident infections (a military conscript cohort and an injection drug user cohort) and in one longitudinal cohort (an HIV-1 vaccine efficacy trial cohort) that also included long-term infections. METHODS: Incidence estimates were generated conventionally (based on the number of annual serocoversions) and by using BED test results in the three cohorts. Adjusted incidence was calculated where appropriate. RESULTS: For each longitudinal cohort the BED incidence estimates and the conventional incidence estimates were similar when only newly infected persons were tested, whether infected with CRF01_AE or subtype B'. When the analysis included persons with long-term infections (to mimic a true cross-sectional cohort), BED incidence estimates were higher, although not significantly, than the conventional incidence estimates. After adjustment, the BED incidence estimates were closer to the conventional incidence estimates. When the conventional incidence varied over time, as in the early phase of the injection drug user cohort, the difference between the two estimates increased, but not significantly. CONCLUSIONS: Evaluation of the performance of incidence assays requires the inclusion of a substantial number of cohort-derived specimens from individuals with long-term HIV infection and, ideally, the use of cohorts in which incidence remained stable. Appropriate adjustments of the BED incidence estimates generate estimates similar to those generated conventionally.
| S-EPMC3048863 | biostudies-other
Project description:Biobanks produce and distribute biospecimens, ensuring their fitness for purpose and accurately qualifying them before distribution. In their efforts toward professionalization, biobanks can nowadays seek certification or accreditation. One of the requirements of these standards is regular participation in Proficiency Testing (PT) programs. An international PT program has been developed and provided to biobanks and other laboratories that perform specific tests to qualify different types of biospecimens. This PT program includes biospecimen testing schemes, as well as biospecimen processing interlaboratory exercises. This PT program supports the development of biobank quality assurance by providing the possibility to assess biobank laboratory performance and useful insights into biobank laboratory method performance characteristics and thus fulfill the demands from accreditation authorities.
| S-EPMC6445200 | biostudies-literature
Project description:Despite rapid task-shifting and scale-up of HIV testing services in high HIV prevalence countries, studies evaluating accuracy remain limited. This study aimed to assess overall accuracy level and factors associated with accuracy in HIV rapid testing in Zambia.Accuracy was investigated among rural and urban HIV testing sites participating in two annual national HIV proficiency testing (PT) exercises conducted in 2009 (n = 282 sites) and 2010 (n = 488 sites). Testers included lay counselors, nurses, laboratory personnel and others. PT panels of five dry tube specimens (DTS) were issued to testing sites by the national reference laboratory (NRL). Site accuracy level was assessed by comparison of reported results to the expected results. Non-parametric rank tests and multiple linear regression models were used to assess variation in accuracy between PT cycles and between tester groups, and to examine factors associated with accuracy respectively.Overall accuracy level was 93.1% (95% CI: 91.2-94.9) in 2009 and 96.9% (95% CI: 96.1-97.8) in 2010. Differences in accuracy were seen between the tester groups in 2009 with laboratory personnel being more accurate than non-laboratory personnel, while in 2010 no differences were seen. In both PT exercises, lay counselors and nurses had more difficulties interpreting results, with more occurrences of false-negative, false-positive and indeterminate results. Having received the standard HIV rapid testing training and adherence to the national HIV testing algorithm were positively associated with accuracy.The study showed an improvement in tester group and overall accuracy from the first PT exercise to the next. Average number of incorrect test results per 1000 tests performed was reduced from 69 to 31. Further improvement is needed, however, and the national HIV proficiency testing system seems to be an important tool in this regard, which should be continued and needs to be urgently strengthened.
| S-EPMC4706302 | biostudies-other
Project description:ObjectiveDevelop a simple method for optimal estimation of HIV incidence using the BED capture enzyme immunoassay.DesignUse existing BED data to estimate mean recency duration, false recency rates and HIV incidence with reference to a fixed time period, T.MethodsCompare BED and cohort estimates of incidence referring to identical time frames. Generalize this approach to suggest a method for estimating HIV incidence from any cross-sectional survey.ResultsFollow-up and BED analyses of the same, initially HIV negative, cases followed over the same set time period T, produce estimates of the same HIV incidence, permitting the estimation of the BED mean recency period for cases who have been HIV positive for less than T. Follow-up of HIV positive cases over T, similarly, provides estimates of the false-recent rate appropriate for T. Knowledge of these two parameters for a given population allows the estimation of HIV incidence during T by applying the BED method to samples from cross-sectional surveys. An algorithm is derived for providing these estimates, adjusted for the false-recent rate. The resulting estimator is identical to one derived independently using a more formal mathematical analysis. Adjustments improve the accuracy of HIV incidence estimates. Negative incidence estimates result from the use of inappropriate estimates of the false-recent rate and/or from sampling error, not from any error in the adjustment procedure.ConclusionsReferring all estimates of mean recency periods, false-recent rates and incidence estimates to a fixed period T simplifies estimation procedures and allows the development of a consistent method for producing adjusted estimates of HIV incidence of improved accuracy. Unadjusted BED estimates of incidence, based on life-time recency periods, would be both extremely difficult to produce and of doubtful value.
| S-EPMC3250478 | biostudies-literature
Project description:In Catalonia, a screening protocol for cervical cancer, including human papillomavirus (HPV) DNA testing using the Digene Hybrid Capture 2 (HC2) assay, was implemented in 2006. In order to monitor interlaboratory reproducibility, a proficiency testing (PT) survey of the HPV samples was launched in 2008. The aim of this study was to explore the repeatability of the HC2 assay's performance. Participating laboratories provided 20 samples annually, 5 randomly chosen samples from each of the following relative light unit (RLU) intervals: <0.5, 0.5 to 0.99, 1 to 9.99, and ?10. Kappa statistics were used to determine the agreement levels between the original and the PT readings. The nature and origin of the discrepant results were calculated by bootstrapping. A total of 946 specimens were retested. The kappa values were 0.91 for positive/negative categorical classification and 0.79 for the four RLU intervals studied. Sample retesting yielded systematically lower RLU values than the original test (P<0.005), independently of the time elapsed between the two determinations (median, 53 days), possibly due to freeze-thaw cycles. The probability for a sample to show clinically discrepant results upon retesting was a function of the RLU value; samples with RLU values in the 0.5 to 5 interval showed 10.80% probability to yield discrepant results (95% confidence interval [CI], 7.86 to 14.33) compared to 0.85% probability for samples outside this interval (95% CI, 0.17 to 1.69). Globally, the HC2 assay shows high interlaboratory concordance. We have identified differential confidence thresholds and suggested the guidelines for interlaboratory PT in the future, as analytical quality assessment of HPV DNA detection remains a central component of the screening program for cervical cancer prevention.
| S-EPMC3993685 | biostudies-literature
Project description:Knowledge of incidence rates of HIV and other infectious diseases is important in evaluating the state of an epidemic as well as for designing interventional studies. Estimation of disease incidence from longitudinal studies can be expensive and time consuming. Alternatively, Janssen et al. (1998, Journal of the American Medical Association 280, 42-48) proposed the estimation of HIV incidence at a single point in time based on the combined use of a standard and "detuned" antibody assay. This article frames the problem from a longitudinal perspective, from which the maximum likelihood estimator of incidence is determined and compared with the Janssen estimator. The formulation also allows estimation for general situations, including different batteries of tests among subjects, inclusion of covariates, and a comparative evaluation of different test batteries to help guide study design. The methods are illustrated with data from an HIV interventional trial and a seroprevalence survey recently conducted in Botswana.
| S-EPMC3449098 | biostudies-literature
Project description:Several laboratory assays on cross-sectional specimens for detecting recent HIV infections were developed, but these assays could not be applied in resource-limited and high HIV-incidence areas. This study describes the development of a rapid assay that can simultaneously detect the presence of HIV-1 antibodies of current and/or recent infection. The dot immuno-gold filtration assay (DIGFA) was used to detect recent infection on the principle of antibody avidity changes between recent and long-term infections. The dot immuno-gold silver staining filtration assay (DIGSSA) increases the sensitivity and accuracy of antibody detection by adding a silver staining step to the DIGFA. In the meantime the digital results were produced by the scanner for ambiguous specimens. Further, HIV-1 routine diagnostic antibody was detected simultaneously for improving practicability. The performance of the assays was then assessed through five serum panels with known serological statuses and seroconversion dates. The proportion of false recent infection (PFR) of the DIGSSA was obtained. Through the optimization of basic parameters for DIGSSA, six specimens were all classified correctly. DIGSSA demonstrated good repeatability and high sensitivity. The agreement of DIGSSA with the BED assay was 92.10% (? = 0.65) and 95.36% with the LAg-Avidity assay (? = 0.75). Moreover, the gray values of DIGSSA correlated well with BED ODn (R2 = 0.9397) and LAg-Avidity ODn (R2 = 0.9549). The PFR of DIGSSA was 2.73%, which was lower than that of the BED assay but higher than that of the LAg-Avidity assay. The DIGSSA can feasibly be applied to detect HIV infection and estimate HIV incidence.
| S-EPMC4981313 | biostudies-literature