Accounting of research participants from screening to data analysis.

<p>Accounting of research participants from screening to data analysis.</p

Boxplots of TFV and TFV-DP concentrations by anatomic site.

<p>Side-by-side boxplots of end-of-period visit data for all participants by anatomic site and dosing regimen are shown. Each box indicates the interquartile range with center bar as median and whiskers 1.5 times the quartile. *Lower quartile (LQ) is below the limit of quantitation (LOQ), only median and above are shown. **Median is below LOQ, so the median of values above the LOQ are shown as a single bar. X-axis key: <i>anatomic location</i>, PBMC peripheral blood mononuclear cells, CVL cervicovaginal lavage, ECC endocervical cytobrush; <i>drug moiety</i>, TFV tenofovir, TFV-DP tenofovir diphosphate; <i>sample timing</i>, C_max peak concentration following dose at clinic visit, C_pre-dose concentration prior to dose at clinic visit, C_all pools values from all participants regardless of scheduled time relative to dose.</p

Concentration ratios between dosing period by anatomic location.

<p>Pairs are included if at least one is above the limit of assay quantitation and the other is above the limit of assay detection. Other pairs are excluded. Serum and PBMC ratios are based on pooled values for data pairs from all times with research participants contributing more than one pair.</p

Ratio of unphosphorylated TFV to phosphorylated TFV-DP by anatomic sampling sites.

<p>Pairs are included if at least one value in the pair is above the limit of assay quantitation and the other is above the limit of assay detection. “N” is the number of pairs available meeting the inclusion criteria above. “Maximum N” is the number of possible pairs if all subjects at all visits provided a sample. C_max only includes US participants where multiple serum samples were available; the pair is defined by serum C_max matched with the corresponding PBMC TFV-DP concentration which is not necessarily peak TFV-DP after the same dose. Subscript “all” indicates that all PBMC-Serum pairs from each sample times are included, with participants contributing multiple pairs. All p<0.001 Wilcoxon signed rank test for TFV fmol/gm vs. TFV-DP fmol/gm. *Insufficient samples above the limit of assay quantitation and detection to estimate reliable medians given the inevaluable excluded pairs.</p

Serum TFV and TFV-DP concentration versus time.

<p>Serum TFV (panel A) and PBMC TFV-DP (panel B) concentration versus time plots are shown for the observed 8 hour interval following a dose in clinic according to dosing regimen. Median with asymmetric upper and lower quartiles is shown. Values are only for the 70 US participants where all 6 PK samples were collected.</p

MTN-001 Study Schema.

<p>Formulations: Oral, 300 mg tenofovir disoproxil fumarate; Vaginal, 1% tenofovir gel.</p><p>Sampling occurs at the 3-week mid-point (blood only) and 6-week end of period visit (blood, PBMC, vaginal biopsy [intensive sites], vaginal fluid, and rectal fluid [Bronx-Lebanon site]).</p><p>Number of samples at each visit varied between intensive (US) and non-intensive (African) clinical sites.</p

Subject Characteristics.

<p>Subject Characteristics.</p

Summary of TFV and TFV-DP concentrations at all sampled anatomic sites.

<p>Data from end-of-period visit showing median (interquartile range) by dosing regimen in common concentration units. Serum TFV C_pre-dose, PBMC TFV-DP C_pre-dose, and cervicovaginal lavage include African clinical sites; other parameters are calculable only for US clinical sites. Rectal sponges are only from one US site. For values below the LLOQ,<[median LLOQ] is shown. Cervicovaginal lavage results were corrected for estimated average 20× dilution of 0.5 mL cervicovaginal fluid in 10 mL lavage fluid <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055013#pone.0055013-Mitchell1" target="_blank">[11]</a>.</p