Mean Recency Period for Estimation of HIV-1 Incidence with the BED-Capture EIA and Bio-Rad Avidity in Persons Diagnosed in the United States with Subtype B

<div><p>HIV incidence estimates are used to monitor HIV-1 infection in the United States. Use of laboratory biomarkers that distinguish recent from longstanding infection to quantify HIV incidence rely on having accurate knowledge of the average time that individuals spend in a transient state of recent infection between seroconversion and reaching a specified biomarker cutoff value. This paper describes five estimation procedures from two general statistical approaches, a survival time approach and an approach that fits binomial models of the probability of being classified as recently infected, as a function of time since seroconversion. We compare these procedures for estimating the mean duration of recent infection (MDRI) for two biomarkers used by the U.S. National HIV Surveillance System for determination of HIV incidence, the Aware BED EIA HIV-1 incidence test (BED) and the avidity-based, modified Bio-Rad HIV-1/HIV-2 plus O ELISA (BRAI) assay. Collectively, 953 specimens from 220 HIV-1 subtype B seroconverters, taken from 5 cohorts, were tested with a biomarker assay. Estimates of MDRI using the non-parametric survival approach were 198.4 days (SD 13.0) for BED and 239.6 days (SD 13.9) for BRAI using cutoff values of 0.8 normalized optical density and 30%, respectively. The probability of remaining in the recent state as a function of time since seroconversion, based upon this revised statistical approach, can be applied in the calculation of annual incidence in the United States.</p></div

Estimated days of mean duration of recent infection (MDRI) and standard error, in parentheses, for BED and BRAI incidence bioassays.

<p>A total of 858 measurements from 209 subjects of 4 cohorts and 749 measurements from 162 subjects of 3 cohorts were used to estimate BED and BRAI MDRI, respectively. Results for five estimation procedures are given.</p

The probability of remaining in the recent state as a function of time since seroconversion for BED and BRAI bioassays.

<p>Model predicted probabilities from five estimation methods are given; blue lines represent the survival methods, green dashed lines the binomial logit, and red dotted line the GAM method. Subject-specific increasing trends in normalized OD or avidity are graphed in the background on the secondary vertical axis. The horizontal dashed line represents the bioassay threshold for classification of recency/non-recency (BED threshold 0.8; BRAI threshold 30%).</p

Characteristics of data used in estimation of MDRI by data source.

<p>The median and interquartile range of distributions are given for the HIV-negative seroconversion interval, i.e., time between last HIV-negative and first HIV-positive tests; the HIV-positive follow-up, reflecting the total duration of observation after testing positive; the number of HIV-positive samples; and the HIV-positive sampling intervals or times between consecutive samples.</p

Comparison of conventionally and BED-estimated incidence in two cohorts.

<p>PY, person-years; CI, 95% confidence interval; BMA, Bangkok Metropolitan authority.</p

Comparison of conventionally and BED-estimated incidence: effect of long term infections.

<p>PY, person-years; CI, 95% confidence interval; LT, long-term infections. Adjustments were done as recommended by Welte et al. 2009 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0014748#pone.0014748-Welte1" target="_blank">[reference 17]</a>.</p