PREDICTIVE EFFECTIVENESS OF ON-DEMAND PRE-EXPOSURE PROPHYLAXIS TO PREVENT HIV
Open Access
- Author:
- Dorabiala, Olga M
- Area of Honors:
- Mathematics
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Dr. Jessica Conway, Thesis Supervisor
Dr. Diane Marie Henderson, Thesis Honors Advisor - Keywords:
- PrEP
HIV
pre-exposure prophylaxis
PK/PD Model
early infection model of HIV
on-demand PrEP
HIV virus dynamics
HIV disease prevention
pharmacokinetic-pharmacodynamic model
mathematical model of HIV - Abstract:
- An important strategy for preventing HIV infection involves taking a drug in case of exposure. Continuous, daily dosing of Truvada, an anti-retroviral HIV drug, with the first dose administered a full month before the initial high-risk incident, is the current CDC recommendation for preventing infection through pre-exposure prophlyaxis (PrEP). However, the IPERGAY study showed that taking only three doses - one before and two following exposure to HIV - may prevent HIV infection almost as effectively as continuous dosing, with the added benefit of smaller quantity of drugs being administered. This is called ``on-demand PrEP''. For this latter strategy, uncertainty exists around the optimum time to start treatment as well as how many doses to take. To address this question, we developed and analyzed a mathematical model of early infection and pre-exposure prophylaxis of HIV infection based on virus dynamics and the pharmacokinetics and pharmacodynamics of Truvada. We ran simulations and analyzed the results in order to come up with predictions and recommendations on the best strategies for disease prevention with regards to when to start and stop treatment and the frequency of doses, within the range one is safely permitted to take. We show that PrEP is likely an effective method for preventing infection and provide more narrow guidelines for a dosing schedule than those used in the IPERGAY study.