Abstract
BackgroundAccurate 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.MethodsWe 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.ResultsMonitoring 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.ConclusionsThese 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.
Highlights
In the last decade, significant national and international efforts have focused on HIV prevention, care, and treatment of HIVinfected individuals in many countries
LAg-Avidity EIA Controls Selected bulk volume HIV-1 positive specimens with optical density (OD) in the dynamic range were chosen as low positive control (LPC), calibrator (CAL), and high positive control (HPC)
CAL was chosen such that its OD value was between 0.6–0.8, with HPC and LPC bracketing the CAL
Summary
Significant national and international efforts have focused on HIV prevention, care, and treatment of HIVinfected individuals in many countries. Major international initiatives such as the President’s Emergency Plan for AIDS Relief (PEPFAR) aims to prevent 12 million new infections. Incidence measurements can help target prevention programs and determine the effectiveness of these programs in reducing HIV infections. Development of a reliable method to estimate HIV-1 incidence has remained elusive [2,3]. Accurate and reliable laboratory methods are needed for estimation of HIV-1 incidence to identify the highrisk 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
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