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The pharmacokinetics of TD* and FTC vary by tissue (24). Data from exploratory pharmacokinetic studies conducted with men and women without HIV infection suggest that maximum intracellular concentrations of tenofovir diphosphate are reached in blood after approximately 20 days of daily oral dosing (25, 26). Current evidence suggests that for both rectal and vaginal exposure, high protection is achieved after 7 days of daily dosing (27). Women need to maintain high adherence to daily dosing of TD*/FTC to maintain adequate drug levels in vaginal/cervical tissues (27). No data are yet available about intracellular drug concentrations in penile tissues susceptible to HIV infection to inform considerations of protection for male insertive sex partners. Limited data exist for transgender and gender-diverse people therefore extra attention to daily dosing is recommended.

Recently WHO recommended that because MSM achieve highly protective levels of PrEP medications with a single loading dose of two PrEP tablets (28, 29), they can take this PrEP loading dose whether they intend to commence daily, or on-demand^† PrEP (6). The ASHM PrEP Guidelines Panel agrees with this recommendation on PrEP dosing initiation for MSM whether they are commencing daily or on-demand^† PrEP.

^† The Therapeutic Goods Administration (TGA) has not approved this regimen in Australia.