Longitudinal HIV-1-specific antibody responses.

<p>The normalized values (A) and avidity index (B), as measured by the Bio-Plex assay, for longitudinal seroconverters were plotted over days since seroconversion. Gray diamonds indicate individual data points and solid black circles represent the curve fit for each graph. Dashed red lines represent the half maximal response of the curve and lower 99.9% confidence limits of the estimate, while the solid black line represents the selected cutoff.</p

Impact of disease progression and antiretroviral use on false-recent rates.

a<p>Includes entire MSM cohort.</p

Bio-Plex assay performance on subtype C specimens.

<p>Bio-Plex assay performance on subtype C specimens.</p

Characterization of the HIV-1-specific Bio-Plex.

a<p>Algorithm cutoffs are listed as the number of analytes that must measure above each analyte-specific cutoff to be considered long-term over the total number of analytes in the algorithm.</p>b<p>Relative % difference from actual population incidence.</p

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

Distribution of age, gender, route of infection, place of presumed infection, and year of diagnosis in Bulgaria.

<p>Distribution of age, gender, route of infection, place of presumed infection, and year of diagnosis in Bulgaria.</p

Inferred genetic relationships of 202 HIV-1 polymerase (<i>pol</i>) sequences from persons in Bulgaria.

<p>Bayesian inference performed using the BEAST software package and a relaxed molecular clock and constant population size tree prior. 170 HIV-1 reference <i>pol</i> sequences were used for genetic comparison. Reference sequences are indicated with a grey diamond. The maximum clade credibility tree is shown. Final alignment length is 804 nucleotides. Posterior probabilities greater than 0.97 at nodes are shown with orange dots. Clades shaded with rose-colored trapezoids indicate possible epidemiologically-linked sequences supported with posterior probabilities ≥0.97, maximum likelihood bootstrap support ≥97%, and having <10% divergence per sampling period. Genotype classification of the Bulgarian sequences is shown with respect to the reference sequences. URFs and rare CRF lineages in Bulgaria are shown with bright green branches. Branches of major subtypes and CRF are highlighted with random colors. All other branches are black.</p