Changes in the probability of testing recent by BED with time since HIV infection.

<p>For PNP = 0 there are no “non-progressors” – <i>i.e.</i> it is assumed that every person, at some point, has a BED OD><i>C</i>, the pre-set OD cut-off. For PNP>0 some people never have an OD><i>C</i>. In both cases, however, it is allowed that some cases may revert, temporarily or permanently – <i>i.e.</i> that the OD declines from >0.8 to <0.8. Note that this implies that the level of ε may vary with the time since seroconversion and, in particular, may not even (as illustrated for simplicity) increase monotonically with time.</p

A. Patterns of changes in BED optical density showing the range of scenarios actually observed in the ZVITAMBO Trial and possible changes before and after the observational period.

<p>Clients were first seen at time 0 and then again a year later. For purposes of illustration it is assumed that all cases had seroconverted two years previously at which time they had a BED OD close to zero. See the text for discussion of possible changes in BED OD before the clients were tested at <i>t</i> = 0 and again after they were tested at <i>t</i> = 1. B. Possible long-term changes in BED OD following HIV infection.</p

Summary of baseline and 12-month postpartum HIV results and, for the latter, of the BED results for HIV positive cases.

<p>Summary of baseline and 12-month postpartum HIV results and, for the latter, of the BED results for HIV positive cases.</p

Fits to the BED OD data for ZVITAMBO mothers providing at least six BED samples following seroconversion.

<p>Fitting the non-linear function given by <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049661#pone.0049661.e036" target="_blank">Equation (9</a>) to the log-transformed BED OD data for 12 different women in the ZVITAMBO Trial who provided either six or seven separate BED results following seroconversion, and where the time between last negative and first positive HIV tests was at most 120 days. Plots of log_e(OD) against estimated time since seroconversion.</p

Graphical approach for estimating the mean recency duration.

<p>The graph shows a scatter plot of all BED OD values obtained from seroconverting women from the ZVITAMBO study, where the time between the last negative and first positive HIV tests did not exceed 120 days and where the woman provided at least four HIV positive samples. Horizontal line marks a pre-set OD cut-off of 0.8; vertical lines mark a pre-set cut-off of <i>T</i> = 365-days and a line whose position can be varied until the number of points in rectangles A and B are the same. Points in the other four rectangles are not used in this estimating procedure.</p

Fits to the BED OD data for a single seroconverting mother from the ZVITAMBO Trial.

<p>Predicted values obtained from: A. LMM. Linear regression of the square root of OD values against log time (<i>t</i>) since the last HIV negative test (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049661#pone.0049661.e031" target="_blank">Equation (7</a>)). B. NLMM (U). Fitting the non-linear function given by <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049661#pone.0049661.e034" target="_blank">Equation (8</a>) to the untransformed BED OD data. C. NLMM (L). Fitting the non-linear function given by <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049661#pone.0049661.e036" target="_blank">Equation (9</a>) to the log-transformed BED OD data. D. Using the fit described in C, but now plotting log_e(OD) on the ordinate.</p

Variability in BED HIV incidence estimates as a function of optical density cut-off (<i>C</i>).

<p>The coefficient of variation for BED HIV incidence estimates obtained using the ZVITAMBO baseline data, as a function of the pre-set optical density cut-off (<i>C</i>). Incidence calculated using <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049661#pone.0049661.e009" target="_blank">Equation (1</a>) with values of estimated by NLMM.</p

Mean recency durations, estimated using different methods, as a function of the BED pre-set optical density cut-off (<i>C</i>).

<p>Mean recency durations (with 95% confidence intervals) estimated using: A. Non-linear mixed modeling (NLMM); linear mixed modeling (LMM); the proportion of recent infections among seroconverters tested at one year postpartum (<i>r</i>/<i>s</i>). B. Survival analysis (SA); graphical analysis (Graph). NLMM estimates, included in both A and B as a reference, increased quadratically with <i>C</i>: OD = −64.4<i>C</i>²+275.3<i>C</i>+17.4 (<i>R</i>²>0.999). The dotted line indicates the greater variability inherent in the graphical method of estimation.</p

Distribution of BED optical density among women at recruitment into the ZVITAMBO Trial.

<p>Distribution of BED optical density among women at recruitment into the ZVITAMBO Trial.</p

HIV incidence, estimated using BED, with the mean recency duration estimated using four different methods.

<p>HIV incidence (with 95% confidence intervals) among women during their first year postpartum in the ZVITAMBO Trial, calculated using estimates of the mean recency duration from non-linear mixed modeling (NLMM), linear mixed modeling (LMM), survival analysis (SA) and graphical analysis (Graph).</p