Impact of dosing strategies on plasma concentrations of tenofovir: Implications in HIV pre-exposure prophylaxis in China

Abstract

Background: Tenofovir disoproxil fumarate has been recommended for pre-exposure prophylaxis (PrEP) to prevent HIV infection. Several studies have shown short but potent intermittent PrEP could provide comparable protection to daily PrEP in men, suggesting such dosing strategy might be useful in Chinese as well. The objective of this study was to evaluate the impact of different dosing strategies on plasma concentrations of tenofovir. Methods: An open label study in 40 Chinese healthy volunteers, randomized to receive the WHO-recommended dose of tenofovir (300 mg) at four different dosing intervals: twice weekly for 4 weeks; once daily for 4 weeks with one missing dose in weeks 2–4; once daily for 4 weeks with two missing doses in weeks 2–4; and once every other day for 12 days. Plasma samples were collected at pre-dose, weekly trough and 24 h post last dose and assayed using HPLC-UV. Results: The tenofovir trough concentrations were below the lower limit of quantification with the twice weekly regimen. The trough concentrations (24 h dosing interval) at the steady state were 51.7 ± 12.1 ng/ml and 53.5 ± 13.8 ng/ml (mean ± SD) in the once daily groups. Missing doses, once or twice weekly, had no significant impact on trough concentrations. Prolongation of dosing interval to 48 h resulted with concentrations at 24 h and 48 h (trough) of ∼40 and 20 ng/ml, respectively. Conclusions: Intermittent tenofovir regimens resulted with remarkably low plasma concentrations in Chinese participants. Missing doses did not affect trough concentrations significantly.

Keywords

• Tenofovir disoproxil fumarate
• Intermittent regimens
• Missing dose
• PrEP