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Quantitative systems pharmacology of HIV PrEP and PEP
Sara Iannuzzi1,2, Lanxin Zhang1,2, Antonia Liebenberg1
1Projektgruppen, Project Group 5, Robert-Koch Institute Berlin, Berlin, Germany.
Introduction:
Soon after their discovery, antiretroviral drugs were used for post-exposure prophylaxis (PEP) and soon after that for preventing mother-to-child transmission (MTCT) of HIV. About 15 years ago, they were first used for pre-exposure prophylaxis (PrEP), which is nowadays widely available across the globe.
Areas Covered:
Quantitative systems pharmacology (QSP) of PrEP and PEP provides a framework to investigate the dynamic interplay of antiviral pharmacology, virology and immunology which may ultimately determine prophylactic efficacy. Following a comprehensive literature search, we will elaborate on the state-of-knowledge and modeling regarding pharmacometrics, viral and immune dynamics and their potential to modulate pharmacokinetic target concentrations for HIV prevention.
Expert Opinion:
QSP modeling can inform the design of clinical trials, which are challenging to conduct due to expenditure, ethics and sample size requirements. Moreover, once clinical data is available, interpreting outcomes is challenging due statistical limitations, the heterogeneous composition of trial arms and heterogeneity in adherence to the intervention. These limitations warrant integrative mathematical modeling to help extract insight, fill persistent knowledge gaps and to optimize PrEP and PEP guidelines based thereon.
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