Grouping Scan analysis.

<p>Sequence fragments of 250 bases incrementing by 100 bases with 100 bootstrap replicates, were used to compare and analyse (a) <i>P.t.troglodytes/P.t.ellioti</i> recombinant FJ98098.1 (b) <i>P.t.ellioti/P.t.troglodytes</i> recombinant FJ98099.1 (c) <i>P.t.schweinfurthii</i> isolate A498266; (d) <i>P.t.troglodytes</i> AM117396 (e) <i>P.t.troglodytes</i> recombinant AB046525 (f) study recombinant <i>Gorilla gorilla</i> HBV sequence (ECO50003); to sequence groups from <i>Gorilla gorilla</i> (red), <i>Pan troglodytes ellioti</i> (blue), <i>Pan troglodytes troglodytes</i> (green), <i>Pan troglodytes verus</i> (yellow), <i>Pan troglodytes schweinfurthii</i> (purple) and human genotype HBV/C (light blue) with respect to A498266. Values >0.5 indicate clustering within the indicated group.</p

Specimen isolation data.

<p>Specimen isolation data.</p

Tree Order Scan of HBV sequences.

<p><b>Figure 2(a)</b>. TreeOrder Scan of HBV sequences, indicating positions of individual sequences (y axis) in Phylogenetic trees generated from sequential 250-base sequence fragments, incrementing by 50 bases. Changes in sequence order as a result of changes in phylogeny at the 70% bootstrap level are shown. Sequences are colour coded by genotype and host species, as indicated by the labels in left and right margin: genotype A, purple; B, light blue; C, wine; D, emerald; E, royal blue; F, orange; G, pale green; H, navy; Gorilla, blue (Gor); Chimpanzee, green (Pan); and Woolly monkey (WM-out-group on line 1), red. For comparison the Tree Order Scan has been aligned with scale genome of HBV (top panel). Recombinant sequences are highlighted as by dashed lines; black gorilla/<i>P.t.e</i> ECO50003LIP3, green FJ798099 <i>P.t.e/P.t.t</i>, pink FJ798098 <i>P.t.e/P.t.t</i>, orange AB046525 <i>P.t.t</i> and purple AF498266 <i>P.t.s </i><b>2(b).</b> Tree Order Scan of HBV sequences, indicating positions of individual sequences (y axis) in phylogenetic trees generated from sequential 250-base sequence fragments, incrementing by 50 bases. Changes in sequence order as a result of changes in phylogeny at the 70% bootstrap level are shown. Sequences are colour coded by host species and sub-species of chimpanzee, as indicated by the labels in left and right margin: <i>Gorilla gorilla</i>, blue (Gor); <i>Pan troglodytes troglodytes</i>, yellow (<i>Ptt</i>); <i>Pan troglodytes ellioti</i>, green (<i>Pte</i>); <i>Pan troglodytes verus</i>, purple (<i>Ptv</i>); <i>Pan troglodytes schweinfurthii</i>, violet (<i>Pts</i>); and <i>Hylobates pileatus</i> (<i>Hyl</i>) (out-group-line 1-GII), red. For comparison the Tree Order Scan has been aligned with scale genome of HBV (top panel). Recombinant sequences are highlighted as by dashed lines; black gorilla/<i>P.t.e</i> ECO50003LIP3, green FJ798099 <i>P.t.e/P.t.t</i>, brown FJ798098 <i>P.t.e/P.t.t</i>, orange AB046525 <i>P.t.t</i> and blue AF498266 <i>P.t.s.</i></p

Flow chart showing the derivation of study sets meeting meta-analysis inclusion criteria: studies of representative ARV-naïve populations of 25 or more individuals with published RT sequences with or without protease sequences.

<p>Flow chart showing the derivation of study sets meeting meta-analysis inclusion criteria: studies of representative ARV-naïve populations of 25 or more individuals with published RT sequences with or without protease sequences.</p

Temporal trends in the yearly proportion of individuals having one or more surveillance drug-resistance mutations in Latin America/Caribbean.

<p>The <i>x</i>-axes represent the calendar year of the sample. The diameter of each circle is proportional to the number of samples sequenced that year. The fitted line shows the fixed effect of sample year in generalized linear mixed model regression.</p

A snapshot of an interactive map plotting the prevalence of transmitted drug resistance in 111 countries from 287 studies between 2000 and 2013 (http://hivdb.stanford.edu/surveillance/map/).

<p>Each study is represented by a circle. The size of the circle is proportional to the number of individuals in the study. The circle color indicates the prevalence of overall TDR in the study: white (<2.5%), pale yellow (2.5% to 4.9%), orange (5.0% to 9.9%), and red (≥10.0%). Each study can also be located on a sidebar, which lists each publication, percent overall TDR, number of individuals, and the country (or countries) where the study was conducted. Clicking on a sidebar row or a study circle in the interactive version of the map at <a href="http://hivdb.stanford.edu/surveillance/map/" target="_blank">http://hivdb.stanford.edu/surveillance/map/</a> generates a pop-up box with additional information including a link to the appropriate PubMed reference, the TDR prevalence by ARV class, the median year of virus sampling, the source of virus isolation, the mechanism of participant recruitment, and the virus subtype distribution (a pop-up box of the study Bila13 is shown as an example). The complete set of data associated with a study can be reviewed by clicking on the “Resistance (%)” link either on the sidebar or within the study circle pop-up menu.</p

Yearly change in odds of transmitted drug resistance in generalized linear mixed regression models in geo-economic regions with and without ARV scale-up.

<p>Three studies from North Africa and two studies from Australia were excluded. Latin America/Caribbean includes three studies from Caribbean countries.</p><p>^aFor each region, a generalized linear mixed model was used to assess the yearly change in the odds (OR) of TDR accounting for study heterogeneity using the R package lme4. The model included a categorical outcome variable indicating the presence or absence of TDR and two explanatory variables: years since scale-up (or the sample year) as a fixed-effect term and the study as a random-effect term.</p><p>^bYearly change in the odds of TDR since ARV scale-up in regions with national ARV scale-up programs and for each sample year in regions without national ARV scale-up; the number of individuals in each region (<i>n</i>) is indicated.</p><p>Yearly change in odds of transmitted drug resistance in generalized linear mixed regression models in geo-economic regions with and without ARV scale-up.</p

The prevalence of each NRTI-associated surveillance drug-resistance mutation in this meta-analysis versus in NRTI-experienced individuals in the same regions according to HIVDB.

<p>The Spearman’s rank correlation coefficient (rho) and the <i>p-</i>value are shown in each plot. The number of isolates from NRTI-experienced individuals were 4,522, 2,218, 4,164, and 13,522 for SSA, SSEA, Latin America/Caribbean, and the pooled upper-income countries (UIC; Europe, North America, and upper-income Asian countries), respectively.</p

Estimated levels of predicted genotypic drug resistance for viruses with and without surveillance drug-resistance mutations.

<p>HIVDB genotypic resistance interpretation program predictions of NRTI, NNRTI, and PI resistance for all virus samples using NRTI, NNRTI, and PI SDRMs, respectively (A). HIVDB program predictions of NRTI, NNRTI, and PI resistance in all samples without an SDRM (B). NRTIs: zidovudine (AZT), abacavir (ABC), lamivudine (3TC), and tenofovir (TDF); NNRTIs: nevirapine (NVP), efavirenz (EFV), rilpivirine (RPV), and etravirine (ETR); PIs: lopinavir (LPVr), atazanavir (ATVr), and darunavir (DRVr). UIC, upper-income countries.</p

Temporal trends in the yearly proportion of individuals having one or more surveillance drug-resistance mutations in low- and middle-income countries of south and southeast Asia.

<p>The <i>x</i>-axes represent the number of years since ARV scale-up for each isolate. The diameter of each circle is proportional to the number of samples sequenced that year. The fitted line shows the fixed effect of years since ARV scale-up in generalized linear mixed model regression.</p