To validate the BED capture enzyme immunoassay for HIV-1 subtype C and to derive adjustments facilitating estimation of HIV-1 incidence from cross-sectional surveys.
Laboratory analysis of archived plasma samples collected in Zimbabwe.
Serial plasma samples from 85 women who seroconverted to HIV-1 during the postpartum year were assayed by BED and used to estimate the window period between seroconversion and the attainment of a specified BED absorbance. HIV-1 incidences for the year prior to recruitment and for the postpartum year were calculated by applying the BED technique to HIV-1-positive samples collected at baseline and at 12 months.
The mean window for an absorbance cut-off of 0.8 was 187 days. Among women who were HIV-1 positive at baseline and retested at 12 months, a proportion (epsilon) 5.2% (142/2749) had a BED absorbance < 0.8 at 12 months and were falsely identified as recent seroconverters. Consequently, the estimated BED annual incidence at 12 months postpartum (7.6%) was 2.2 times the contemporary prospective estimate. BED incidence adjusted for epsilon was 3.5% [95% confidence interval (CI), 2.6-4.5], close to the 3.4% estimated prospectively. Adjusted BED incidence at baseline was 6.0% (95% CI, 5.2-6.9) and, like the prospective estimates, declined with maternal age. Unadjusted BED incidence estimates were largely independent of age; the pooled estimate was 58% higher than adjusted incidence.
The BED method can be used in an African setting, but further estimates of epsilon and of the window period are required, using large samples in a variety of circumstances, before its general utility can be gauged.
"Among the many laboratory-based incidence assays developed, the most evaluated assay is the immunoglobulin G (IgG)-capture BED- enzyme immunoassay (BED-CEIA) based on measurement of the proportion of HIV-1-specific IgG to total IgG after seroconversion567. Licensing and manufacturing of commercial kits with consistent quality began in 2005 and this assay is currently used globally for population surveillance18910. "
[Show abstract][Hide abstract] ABSTRACT: The HIV-1 BED incidence assay was adopted in China in 2005 for HIV-1 incidence surveillance. A proficiency testing (PT) program was established in 2006 to provide quality assurance services. The BED PT program consisted of two components, an international program provided by the U.S. Centers for Disease Control and Prevention from 2006 and a domestic program started by the National HIV/HCV Reference Laboratory in 2011. Each PT panel consisted of eight coded specimens distributed to participating laboratories semi-annually, and testing results were collected and analyzed. The number of participating laboratories increased progressively from 2006 to 2012. The Chinese HIV-1 incidence laboratory network performed satisfactorily both in international and domestic PT programs. We also demonstrated that the BED assay was highly reproducible among participating laboratories. Our success and lessons learned can be readily replicated in other countries or regions contemplating the establishment of a PT program for assay-based HIV incidence estimation.
[Show abstract][Hide abstract] ABSTRACT: To estimate the incidence of HIV-1 infection among pregnant women from central-western Brazil.
Observational cross-sectional study.
A total of 54,139 pregnant women received antenatal HIV screening from a network of public healthcare centers in 2011. The incidence of confirmed HIV-1 infection was estimated using the Serological Testing Algorithms for Recent HIV Seroconversion (STARHS) methodology and BED-capture enzyme immunoassay (BED-CEIA). The yearly incidence was calculated, and adjusted incidence rates were estimated. For a subgroup of patients, protease and partial reverse transcriptase regions were retrotranscribed from plasma HIV-1 RNA and sequenced after performing a nested polymerase chain reaction.
Of the participants, 20% had a pregnancy before the age of 18 and approximately 40% were experiencing their first pregnancy. Of the 54,139 pregnant women screened, 86 had a confirmed HIV-1 diagnosis, yielding an overall prevalence of 1.59 cases per 1000 women (95% CI 1.27-1.96). A higher prevalence was detected in the older age groups, reflecting cumulative exposure to the virus over time. Among the infected pregnant women, 20% were considered recently infected according to the BED-CEIA. The estimated incidence of HIV infection was 0.61 per 1000 person-years (95% CI 0.33-0.89); the corrected incidence was 0.47 per 1000 person-years (95% CI 0.26-0.68). In a subgroup of patients, HIV-1 subtype C (16.7%) was the second most prevalent form after subtype B (66.7%); BF1 recombinants (11.1%) and one case of subtype F1 (5.5%) were also detected.
This study highlights the potential for deriving incidence estimates from a large antenatal screening program for HIV. The rate of recent HIV-1 infection among women in their early reproductive years is a public health warning to implement preventive measures.
PLoS ONE 11/2013; 8(11):e79189. DOI:10.1371/journal.pone.0079189 · 3.23 Impact Factor
"Currently, the BED assay is the only assay commercially available specifically to measure HIV-1 incidence in cross-sectional populations and is used in more than 50 laboratories worldwide , , , . The assay has high precision , although its accuracy to detect recent infection has been questioned due to false recent classification resulting in elevated incidence estimates , , , . Moreover, recent analysis demonstrated that the assay has a significantly higher mean duration of recency in African populations than in other populations . "
[Show abstract][Hide abstract] ABSTRACT: Accurate and reliable laboratory methods are needed for estimation of HIV-1 incidence to identify the high-risk populations and target and monitor prevention efforts. We previously described a single-well limiting-antigen avidity enzyme immunoassay (LAg-Avidity EIA) to detect recent HIV-1 infection.
We describe here further optimization and characterization of LAg-Avidity EIA, comparing it to the BED assay and a two-well avidity-index (AI) EIA. Specimen sets included longitudinal sera (n = 393), collected from 89 seroconverting individuals from 4 cohorts representing 4 HIV-1 subtypes, and sera from AIDS patients (n = 488) with or without TB co-infections from 3 different cohorts. Ninety seven HIV-1 positive specimens were purchased commercially. The BED assay, LAg-Avidity EIA, AI-EIA and HIV serology were performed, as needed.
Monitoring quality control specimens indicated high reproducibility of the LAg-Avidity EIA with coefficient of variation of <10% in the dynamic range. The LAg-Avidity EIA has an overall mean duration of recency (ω) of 141 days (95% CI 119-160) at normalized optical density (ODn) cutoff of 1.0, with similar ω in different HIV-1 subtypes and populations (132 to 143 days). Antibody avidity kinetics were similar among individuals and subtypes by both the LAg-Avidity EIA and AI-EIA compared to the HIV-IgG levels measured by the BED assay. The false recent rate among individuals with AIDS was 0.2% with the LAg-Avidity EIA, compared to 2.9% with the BED assay. Western blot profiles of specimens with increasing avidity confirm accurate detection of recent HIV-1 infections.
These data demonstrate that the LAg-Avidity EIA is a promising assay with consistent ω in different populations and subtypes. The assay should be very useful for 1) estimating HIV-1 incidence in cross-sectional specimens as part of HIV surveillance, 2) identifying risk factors for recent infections, 3) measuring impact of prevention programs, and 4) studying avidity maturation during vaccine trials.
PLoS ONE 03/2012; 7(3):e33328. DOI:10.1371/journal.pone.0033328 · 3.23 Impact Factor
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