Timeline and summary of data estimating dates of transmission relative to the initiation of therapy.

<p>A. A timeline (in days) is shown relative to the date of initiation of therapy (D₀) for both Case A and Case B. Dates are shown for the proximal time prior to therapy when the viral load in the index was determined along with the proximal date after the initiation of therapy when the index had a viral RNA load below 400 copies/ml. Similarly, the date proximal to but before the date of initiation of therapy when the partner was HIV- (less than 40 copies/ml) and when the partner was diagnosed by western blot analysis (WB) as being HIV+. B. Estimates of the date of transmission to the newly infected partner are shown by the colored horizontal lines on the same timeline as in Panel A, shown separately for Case A and Case B. The gray background indicates the period on therapy for the index. The small black vertical open boxes indicate the dates of the last HIV- sample from each partner, and these boxes are preceded by a black vertical dashed line to indicate the eclipse period (7 days) when transmission could have occurred but not been detected in the blood. The vertical red boxes indicate the dates of the first HIV+ sample in the partners. The horizontal lines represent the range of the possible dates of transmission inferred using the several different approaches. The length of the horizontal line is meant to indicate the uncertainty associated with the estimate. The vertical bar on the horizontal line represents the most likely date of transmission given the sequence diversity. Estimates for the transmission date are shown for serology (in orange), sequence diversity using the Poisson Fitter (in purple), and for expansion of the sequence population in the partner using BEAST (i.e. time to most recent common ancestor/MRCA; in dark blue). For the serology estimate we used the shortest period of time needed for a newly infected person to progress to Fiebig Stage V (23 days) or Fiebig Stage VI) (55 days). Since an infected person can stay in either of these stages for an extended period of time these lines are left-censored at the earliest possible transmission date (dashed black vertical line) given the negative HIV-1 viral RNA load assay plus the eclipse period.</p

Phylogenetic analysis of viral populations in the index and partner.

<p>The program BEAST was used to recreate phylogeny (Bayesian skyline) of the viral <i>env</i> sequences generated from the index (black) and partner (red) for Case A (Panel A) and Case B (Panel B). Each tip (with dot) of the tree is an individual sequence. For Case A, sequences from the partner are dispersed among the sequences from the index, indicating the transmission of at least four variants (seen as four discrete positions in the tree where one or more red dots occur). For Case B, the sequences from the partner represent a single lineage/cluster, indicative of transmission of a single variant. The tree structure moves back in time from right to left as indicated by the arrow at the bottom and with the scale shown for 100 days. The tips of the tree are displaced to correspond to the date the sample was taken that gave rise to those sequences. Each internal node/branch point in the tree represents the inferred most recent common ancestor (MRCA) of all sequences that appear to the right of the node, with the position of each node given an estimated date from the date the partner's infection was detected. The dates (in days) of the MRCA within each partner (interpreted as the date expansion of the virus population started after the transmission event) are indicated (40 days for Case A; 84 days for Case B), and the relevant nodes circled. The numbers in small font indicate the estimated error in the dating of each node. The time to MRCA was estimated from two independent runs which were combined, the HKY substitution model, estimated base frequencies, Gamma site heterogeneity model with 4 gamma categories, a strict clock with a fixed mutation rate of 1.5×10⁻⁵, partner tip dating, and the Bayesian skyline tree model.</p

Data obtained using BEAST analysis, the Poisson Fitter tool, and serological analysis are expressed as the number of days between the estimated date of HIV-1 transmission and HIV-1 diagnosis in the newly-infected partner. These data are also shown in Figure 1B, expressed as days before or after ART initiation in the index.

a<p>HIV-1 diagnosis indicates the number of days between ART initiation in the index and HIV-1 diagnosis in the partner (first HIV-positive sample).</p>b<p>Estimate of the time between HIV-1 transmission and HIV-1 diagnosis in the newly-infected partner based on BEAST analysis.</p>c<p>Estimate of the time between HIV-1 transmission and HIV-1 diagnosis in the newly-infected partner based on use of the Poisson Fitter (Case A only).</p>d<p>The table shows the earliest and average number of days between HIV-1 transmission and the Fiebig stage of each of the newly-infected partners, based on Western blot analysis. The partner in Case A was Fiebig stage V; the partner in Case B was Fiebig Stage VI <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071557#pone.0071557-Fiebig1" target="_blank">[12]</a>; a 7-day eclipse period was included in the calculations.</p

Estimated coverage compared with the first two 90 targets extrapolated to the total adult population.

<p>The red line shows the 90% target for first two of the 90-90-90 targets. Dark blue bars show the estimated proportion of HIV+ adults who knew their status (first 90 target) and the estimated proportion of those who knew their HIV+ status who were on ART (second 90 target), pre-intervention. Red bars show the same estimated proportions, post-intervention. ART, antiretroviral therapy.</p

First two 90 target estimates by sex and age group in those consenting to the PopART intervention and extrapolated to the total adult population.

<p>The red line shows the 90% target for first two of the 90-90-90 targets. The first 90 target is proportion of individuals with knowledge of HIV-positive status, and the second 90 target is proportion of known HIV-positive individuals on antiretroviral therapy. CHiP, community HIV-care provider.</p

Estimated proportions of HIV+ individuals who knew their status and who were on ART before the CHiP visit, immediately after the CHiP visit, and at the end of Round 1, in those consenting to the intervention.

<p>Estimated proportions of HIV+ individuals who knew their status and who were on ART before the CHiP visit, immediately after the CHiP visit, and at the end of Round 1, in those consenting to the intervention.</p

Overview of design of the HPTN 071 (PopART) trial.

<p>ART, antiretroviral therapy; TB, tuberculosis.</p

Estimated coverage compared with the first two 90 targets in those consenting to the PopART intervention.

<p>Dark blue bars show the estimated proportion of HIV+ adults who knew their status (first 90 target) and the estimated proportion of those who knew their HIV+ status who were on ART (second 90 target), pre-intervention. Red bars show the same estimated proportions, post-intervention. ART, antiretroviral therapy.</p

Overall estimates of proportion of HIV+ adults on ART by age group and sex in those consenting to the PopART intervention and extrapolated to the total adult population.

<p>The red line shows the cumulative 81% target based on first two of the 90-90-90 targets. ART, antiretroviral therapy; CHiP, community HIV-care provider.</p

Cascade of care from enumeration of household members through ART initiation during the first annual round of the PopART intervention.

<p>ART, antiretroviral therapy.</p