Background
Pre- and post-exposure prophylaxis (PrEP and PEP) are key strategies to prevent HIV infection. While the efficacy of PrEP has been elucidated in many randomized clinical trials, corresponding data for PEP is challenging to obtain in a controlled setting. Consequently, it is almost impossible to study the impact of PEP initiation delay and PEP duration on HIV risk reduction clinically to inform PEP recommendations.
Methods
We employed pharmacokinetics, pharmacodynamics, and viral dynamics models, incorporating individual factors such as self-start PEP and PEP 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 an FTC/TDF backbone. Moreover, we study PEP efficacy in the context of PrEP-to-PEP transitions.
Results
Our simulations indicate that early initiation of PEP is critical for reducing HIV transmission risk. We found that 2-drug (FTC/TDF) PEP may offer insufficient protection when initiated >1hour post-exposure. When adding dolutegravir (DTG) as a third drug, early initiation was still a critical factor, however, ≈90% efficacy could be achieved when PEP was initiated within 48 hours post-exposure and taken for at least 28 days. If 2-drug (FTC/TDF) PEP was initiated within 24hours post-exposure, DTG may be added several days later to still achieve >90% protection. When investigating PrEP-to-PEP transitions, we observed that preceding PrEP can (i) contribute directly to prophylactic efficacy, and (ii) 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 (<48hours) PEP initiation, preferably with three drugs taken for 28 days. Self-starting 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, where we find that two drug PEP may be possible in situations where PrEP had recently been taken by the exposed individual.
Table or Figure
