<. difference in medication focus between appointments. We recruited 24 lovers to take into account potential participant drop-out. Outcomes Tenofovir Medication Concentrations Are Decreased Pursuing Coitus Demographics are summarized in Supplementary Desk 1. All 24 lovers finished the baseline (no gel) combined sex/no sex appointments and the ?one hour MGC34923 gel combined visits; 22 finished the combined ?24 hour visits, and 23 completed the BAT visit. The median time taken between sex and test collection was one hour 52 mins (range, one hour 2 mins to 3 hours 17 mins). The CVL TFV medication focus was 72.2% (37.5%) (median, interquartile range [IQR]) lower when gel was applied 1 hour before sex compared with without sex (= .0009; Figure ?Figure1,1, Table ?Table2).2). CVL concentrations were lower when ?24 hour dosing was compared with ?1 hour dosing and were 78.2% (33%) lower following sex when compared with the ?24 hour pair (< .0001). Applying another dose of gel approximately 1 hour after sex (BAT) resulted in concentrations that were at least as great as those detected without sex. There was a modest increase in CVL protein concentration after sex (Supplementary Table 2), but the differences in drug concentrations remained significant when adjusted for protein. Table 2. Tenofovir and TenofovirCDiphosphate Concentrations in Different Compartments Figure 1. Tenofovir (TFV) drug levels are reduced in cervicovaginal lavage (CVL) samples following unprotected sex. The concentration of TFV in CVL at each visit was measured (ng/mL); samples with drug levels below the lower limits of quantification (LLOQ) were ... Vaginal and cervical tissue concentrations fell by a median of 75.1% (65.2%; = .001; Figure ?Figure22= .061; Figure ?Figure22= .0003) and 54.6% (55.2%; = .0009), respectively, at ?24 537049-40-4 supplier hours compared with matched no sex visits (Table ?(Table2).2). Adding a 537049-40-4 supplier post-coital dose significantly increased vaginal and cervical tissue TFV levels compared with the ?1 hour gel/sex visit (< .0001; Table ?Table22). Figure 2. Tenofovir (TFV) drug levels are reduced in vaginal and cervical tissue following unprotected sex. The concentrations of TFV in vaginal (= .023), and increased further with BAT dosing (= .0045). Plasma concentrations with ?24 hour dosing were lower 537049-40-4 supplier and unaffected by sex. Low TFV concentrations in rectal sponge samples were also 537049-40-4 supplier unaffected by sex (Table ?(Table22). TFVCDP Concentrations Are Reduced Cervical, however, not Genital, Tissue Pursuing Coitus Cervical cells concentrations of TFVCDP reduced by 65.5% (53.4%) when gel was applied one hour 537049-40-4 supplier before sex weighed against zero sex (= .023) and increased 62.2% (57.2%; = .003) following yet another post-coital dosage (Shape ?(Shape33< .001) following sex from set up a baseline of 9.09% (41.84%) to 55.46% (53.92%) and additional risen to 99.4% (7.16%) if gel was applied one hour ahead of sex (< .001 weighed against no gel/sex). Nevertheless, the anti-HIV activity improved even more to 76 modestly.68% (56.69%) if gel was used 14 hours ahead of sex (< .05). Anti-HIV activity was highest in CVL acquired after BAT dosing (99.81% [0.41%]; < .001; Shape ?Shape4).4). There is no factor in anti-HIV activity when the combined ?one hour visits had been compared. However, there is a little but significant reduction in anti-HIV activity when the combined ?24 hour visits were compared (82.07% [51.10%] no sex vs 76.68% [56.69%] postcoital; = .04). The.