Modeling PrEP-on-demand strategies to prevent HIV transmission
In 2010, analysis of the iPrEx study results demonstrated that daily dosing with antiretroviral therapy (ART) in advance of exposure to HIV, termed pre-exposure prophylaxis (PrEP), can significantly reduce the risk of HIV transmission and population spread. However, daily adherence to a drug regimen can be difficult to maintain and may come with side-effects. In contrast, the IPERGAY study published in 2015 suggested that short-term use around the time of exposure may be just as effective at reducing HIV risk as daily use. Here we investigate short-term use, termed “on-demand” or “event-based” PrEP. We aim to make model-based predictions of effective on-demand drug regimen. Focusing on transmission through sexual exposure, we incorporate a deterministic model of tissue-level pharmacokinetics and pharmacodynamics (PK/PD) of Truvada into a branching-process model of early HIV infection. Thus, we predict the risk of HIV transmission and risk reduction associated with dose size and timing relative to exposure. To evaluate effectiveness of dosing strategies, we simulate strategies by sampling a virtual population and performing extensive sensitivity analyses. Hence, we aim to identify practical dosing strategies that most effectively reduce risk of HIV transmission through sexual exposure.