Modelling the impact of initiation delay, duration and prior PrEP on the efficacy of post‐exposure prophylaxis containing a tenofovir/emtricitabine backbone

Introduction Pre‐ and post‐exposure prophylaxis (PrEP and PEP) are important pillars of the HIV prevention portfolio to reduce the risk of acquisition just before or after HIV exposure. While PrEP efficacy has been elucidated in many randomized clinical trials, corresponding data for PEP is extremel...

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Vydáno v:Journal of the International AIDS Society Ročník 28; číslo S1; s. e26454 - n/a
Hlavní autoři: Zhang, Lanxin, Collins, Simon, Fox, Julie, Kleist, Max
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland John Wiley & Sons, Inc 01.06.2025
John Wiley and Sons Inc
Wiley
Témata:
Anti-HIV Agents - administration & dosage
Anti-HIV Agents - pharmacokinetics
Antiretroviral drugs
Binomial distribution
Chemoprevention - methods
Clinical trials
Disease prevention
Drug dosages
Emtricitabine - administration & dosage
Emtricitabine - pharmacokinetics
Emtricitabine - therapeutic use
Exposure
Health risks
HIV
HIV Infections - prevention & control
Human immunodeficiency virus
Humans
Infections
Male
mathematical modelling
Mathematical models
Ordinary differential equations
Pharmacokinetics
Post-Exposure Prophylaxis - methods
post‐exposure prophylaxis
Pre-Exposure Prophylaxis - methods
pre‐exposure prophylaxis
Probability
Prophylaxis
quantitative systems pharmacology
Risk reduction
TDF/FTC
Tenofovir - administration & dosage
Tenofovir - pharmacokinetics
Time Factors
Treatment Outcome
Vagina
Viruses
pre‐exposure prophylaxis
TDF/FTC
mathematical modelling
HIV
post‐exposure prophylaxis
quantitative systems pharmacology
ISSN:1758-2652, 1758-2652
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Shrnutí:Introduction Pre‐ and post‐exposure prophylaxis (PrEP and PEP) are important pillars of the HIV prevention portfolio to reduce the risk of acquisition just before or after HIV exposure. While PrEP efficacy has been elucidated in many randomized clinical trials, corresponding data for PEP is extremely difficult to obtain in a controlled setting. Consequently, it is almost impossible to study the impact of PEP initiation delay and duration on HIV risk reduction clinically, which would inform recommendations on PEP use. Methods We employ pharmacokinetics, pharmacodynamics and viral dynamics models, along with individual factors, such as drug adherence to investigate the impact of initiation delay and PEP duration on HIV risk reduction. We evaluated PEP using two‐ and three‐drug regimens with a TDF/FTC backbone. Moreover, we study PEP efficacy in the context of PrEP‐to‐PEP transitions. Results In our simulations, early initiation of PEP emerged as a pivotal factor for HIV risk reduction. We found that 2‐drug (TDF/FTC) PEP may insufficiently protect when initiated > 1 hour post‐exposure. When adding a third drug, early initiation was still a critical factor; however, over 90% efficacy could be achieved when PEP was initiated 48 hours post‐exposure and taken for at least 14–28 days, depending on the efficacy of the third‐drug component. When investigating PrEP‐PEP transitions, we observed that preceding PrEP can (1) contribute directly to prophylactic efficacy, and (2) boost subsequent PEP efficacy by delaying initial viral dynamics and building‐up drug concentrations, overall facilitating self‐managed transitioning between PrEP and PEP. Conclusions Our study confirms the critical role of early (< 48 hours) PEP initiation, preferably with three drugs taken for 28 days. Self‐start with TDF/FTC and later addition of a third drug is better than not self‐starting. Furthermore, our study highlights the synergy between recent PrEP intake and PEP and may help to inform recommendations on PEP use.
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ISSN:1758-2652
1758-2652
DOI:10.1002/jia2.26454