Tenofovir disoproxil fumarate:emtricitabine nucleotide ratios in blood and rectal tissue of cisgender vs transgender participants. Ratios of active metabolites (TFVdp and FTCtp) to competitive substrates (dATP and dCTP) are plotted in the blood (A, B) and rectal tissue (C, D) for cisgender men and women (n = 8) vs transgender women (n = 4). PBMC dATP and dCTP values were missing for 2 cisgender men omitted from analysis. In rectal tissue, 2/12 dATP and 1/12 dCTP measurements were BLQ and imputed at the sample-specific lower limit of quantification to calculate the nucleotide ratio. The rectal FTCtp:dCTP nucleotide ratio for 3 individuals (2 cisgender women and 1 cisgender man) for whom both concentration values were BLQ were omitted from analysis. Previously published [11] monotherapy 90% effective concentration (EC90) target ratios are denoted by dashed reference lines on each graph. A Mann-Whitney rank sum t test was performed to detect between-cohort differences. The ratio of TFVdp:dATP in rectal tissue was 7-fold lower among transgender women compared to cisgender participants (P = .03). Abbreviations: BLQ, below the limit of quantification; dATP, deoxyadenosine-triphosphate; dCTP, deoxycytidine-triphosphate; FTCtp, emtricitabine-triphosphate; EC90, PBMC, peripheral blood mononuclear cell; TFVdp, tenofovir-diphosphate.