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  • Showing results for Pharmacokinetics[Title] AND Pharmacodynamics[Title] AND Reverse[Title] AND Transcriptase[Title] AND Inhibitor[Title] AND Prophylactic[Title] AND Efficacy[Title] AND against[Title] AND HIV-1[Title] AND Infection[Title]. Your search for Pharmacokinetics and Pharmacodynamics of the Reverse Transcriptase Inhibitor Tenefovir and Prophylactic Efficacy against HIV-1 Infection retrieved no results.
PLoS One. 2012;7(7):e40382. doi: 10.1371/journal.pone.0040382. Epub 2012 Jul 11.

Pharmacokinetics and pharmacodynamics of the reverse transcriptase inhibitor tenofovir and prophylactic efficacy against HIV-1 infection.

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Department of Mathematics and Computer Science, Free University Berlin, Berlin, Germany.

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  • PLoS One. 2012;7(11). doi:10.1371/annotation/fb73d0f4-1cd8-481d-bddd-20439896102a.


Antiviral pre-exposure prophylaxis (PrEP) through daily drug administration can protect healthy individuals from HIV-1 infection. While PrEP was recently approved by the FDA, the potential long-term consequences of PrEP implementation remain entirely unclear. The aim of this study is to predict the efficacy of different prophylactic strategies with the pro-drug tenofovir-disoproxil-fumarate (TDF) and to assess the sensitivity towards timing- and mode of TDF administration (daily- vs. single dose), adherence and the number of transmitted viruses. We developed a pharmacokinetic model for TDF and its active anabolite tenofovir-diphosphate (TFV-DP) and validated it with data from 4 different trials, including 4 distinct dosing regimes. Pharmacokinetics were coupled to an HIV model and viral decay following TDF mono-therapy was predicted, consistent with available data. Subsequently, a stochastic approach was used to estimate the % infections prevented by (i) daily TDF-based PrEP, (ii) one week TDF started either shortly before, or -after viral exposure and (iii) a single dose oral TDF before viral challenge (sd-PrEP). Analytical solutions were derived to assess the relation between intracellular TFV-DP concentrations and prophylactic efficacy. The predicted efficacy of TDF was limited by a slow accumulation of active compound (TFV-DP) and variable TFV-DP half-life and decreased with increasing numbers of transmitted viruses. Once daily TDF-based PrEP yielded [Formula: see text]80% protection, if at least 40% of pills were taken. Sd-PrEP with 300 mg or 600 mg TDF could prevent [Formula: see text]50% infections, when given at least before virus exposure. The efficacy dropped to [Formula: see text]10%, when given 1 h before 24 h exposure. Efficacy could not be increased with increasing dosage or prolonged administration. Post-exposure prophylaxis poorly prevented infection. The use of drugs that accumulate more rapidly, or local application of tenofovir gel may overcome the need for drug administration long before virus exposure.

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