Determination of Mean Recency Period for Estimation of HIV Type 1 Incidence with the BED-Capture EIA in Persons Infected with Diverse Subtypes

Abstract

The IgG capture BED enzyme immunoassay (BED-CEIA) was developed to detect recent HIV-1 infection for the estimation of HIV-1 incidence from cross-sectional specimens. The mean time interval between seroconversion and reaching a specified assay cutoff value [referred to here as the mean recency period (ω)], an important parameter for incidence estimation, is determined for some HIV-1 subtypes, but testing in more cohorts and new statistical methods suggest the need for a revised estimation of ω in different subtypes. A total of 2927 longitudinal specimens from 756 persons with incident HIV infections who had been enrolled in 17 cohort studies was tested by the BED-CEIA. The ω was determined using two statistical approaches: (1) linear mixed effects regression (ω(1)) and (2) a nonparametric survival method (ω(2)). Recency periods varied among individuals and by population. At an OD-n cutoff of 0.8, ω(1) was 176 days (95% CL 164-188 days) whereas ω(2) was 162 days (95% CL 152-172 days) when using a comparable subset of specimens (13 cohorts). When method 2 was applied to all available data (17 cohorts), ω(2) ranged from 127 days (Thai AE) to 236 days (subtypes AG, AD) with an overall ω(2) of 197 days (95% CL 173-220). About 70% of individuals reached a threshold OD-n of 0.8 by 197 days (mean ω) and 95% of people reached 0.8 OD-n by 480 days. The determination of ω with more data and new methodology suggests that ω of the BED-CEIA varies between different subtypes and/or populations. These estimates for ω may affect incidence estimates in various studies.

Poor Performance of the Determine HIV-1/2 Ag/Ab Combo Fourth-Generation Rapid Test for Detection of Acute Infections in a National Household Survey in Swaziland

“…First, total IgG levels are significantly higher in Africans than in individuals from Western countries due to exposure to multiple pathogens (39). This increased IgG level may interfere with the detection of p24 antigen due to nonspecific binding to the antigen.…”

Impact of HIV Subtype on Performance of the Limiting Antigen-Avidity Enzyme Immunoassay, the Bio-Rad Avidity Assay, and the BED Capture Immunoassay in Rakai, Uganda

“…17,19 The performance of serologic HIV incidence assays has been shown to vary by HIV subtype. [20][21][22][23] For example, among individuals infected for 2 or more years, being misclassified as assay positive is more likely in subtype D infection than subtype A infection. 18,24 In addition, among those with long-standing subtype D infection, women are significantly more likely to be misclassified as assay positive than men.…”

Assessment of Ambiguous Base Calls in HIV-1 pol Population Sequences as a Biomarker for Identification of Recent Infections in HIV-1 Incidence Studies

“…This allows recent and nonrecent infections to be distinguished by serology-based HIV-1 incidence assays in which the increase in the proportion of HIV-specific antibodies (2), the avidity of HIV-specific antibodies (3,4), or a combination of HIV-specific antibody level and avidity (5) is measured. Unfortunately, samples from individuals infected with HIV-1 non-B subtypes (6,7), from elite controllers (8), from individuals treated with antiretroviral drugs (8,9), and from individuals with advanced stages of disease (7,9) can be misclassified on the basis of serological criteria because of delayed or reduced production of HIV-specific antibodies. Nonserological HIV-1 incidence assays (10,11) and algorithms combining serological and nonserological biomarkers have therefore been developed (12,13).…”