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Why is it important?

NRTIs are an important class of antiretroviral compounds used for HIV-1 treatment. Recently, members of this class (tenofovir and emtricitabine) have been repurposed for HIV-1 pre-exposure prophylaxis. Before our study, it was not clear how target inhibition at the molecular level translates into clinical efficacy. Thus, it was not possible to assess the potential of NRTIs for PrEP without clinical testing. We validated a mechanistic 'bottom-up' MOA model for NRTIs, which confirms that we understand how drug interference at the molecular level translates into clinical markers. Moreover, we can then use the 'bottom-up' model to translate in vitro measurable parameters to measures of clinical relevance. This also allows to assess the potential of any NRTI when used in PrEP prior to clinical testing.

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This page is a summary of: Top-down and bottom-up modeling in system pharmacology to understand clinical efficacy: An example with NRTIs of HIV-1, European Journal of Pharmaceutical Sciences, October 2016, Elsevier,
DOI: 10.1016/j.ejps.2016.01.016.
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