| |
Optimizing On-Demand Tenofovir Disoproxil Fumarate/Emtricitabine Dosing in Women for HIV Prevention
|
| |
| |
The Journal of Infectious Diseases, 1 September 2025
Download the PDF here
Download the PDF here
Abstract
Using an established pharmacokinetic/pharmacodynamic tissue model of tenofovir disoproxil fumarate/emtricitabine for HIV pre-exposure prophylaxis (PrEP), we predict that adding a fourth day of dosing to the 3-day IPERGAY on-demand PrEP regimen (currently approved for men/transgender women who have sex with men) will be efficacious for on-demand dosing in cisgender women.
DISCUSSION
Our 3-day investigational regimens of 2-2-1 and 2-2-2 had mild increases (approximately 20% and approximately 30%, respectively), achieving EC90 after 7 days compared with the reference regimen, which can likely be attributed to a higher total dose administered. A similar trend was observed in the 4-day regimens, where a higher total dose (such as in 2-2-1-1 compared to 2-1-1-1) resulted in higher relative proportions achieving EC90 at 7 and 10 days. Interestingly, however, adding an additional day of dosing increased the proportion of those reaching EC90 at 7 days, even when the total dose administered was conserved. For example, the 2-2-1 and 2-1-1-1 regimens both have a total dose of 1500 mg TDF/1000 mg FTC, but the 2-1-1-1 regimen had about a 15% increase in EC90 proportion at 7 days versus the 2-2-1. Similarly, the 2-2-1-1 and 2-2-2 regimens both have a total dose of 1800 mg TDF/1200 mg FTC, but the 2-2-1-1 regimen had about an 8% increase in EC90 proportion at 7 days.
---------------------------
On-Demand Dosing of HIV Preexposure Prophylaxis for Women: Has Their Time Finally Come?
The Journal of Infectious Diseases, 09 December 2025
Human immunodeficiency virus (HIV-1)/AIDS remains the leading cause of death worldwide among women of reproductive age [1]. Preexposure prophylaxis (PrEP) has been shown to significantly reduce the risk of HIV acquisition in women, particularly when adherence is high [2–4]. However, current clinical guidelines recommend only 4 systemic PrEP options for women: daily coformulated emtricitabine/tenofovir disoproxil fumarate (F/TDF) [5], injectable cabotegravir administered bimonthly [5], injectable lenacapavir administered semiannually [6], and, most recently, daily F/tenofovir alafenamide (F/TAF) [6]. On-demand PrEP taken as a 2–1–1 regimen (2 F/TDF tablets 2–24 hours before sex, and 1 tablet each 24 and 48 hours after sex) has been shown to be effective in men who have sex with men (MSM) [7], but there have been no studies powered for efficacy to date of on-demand dosing for women, despite 10 years having passed since the original efficacy study in MSM was published. Although widespread excitement exists about long-acting PrEP agents, some women do not want injectables [8] or need or would like oral regimens delivered less frequently than daily [9].
An on-demand oral regimen would allow women demedicalized PrEP delivery that could simultaneously overcome some of the societal and structural barriers, such as stigma and relationship power dynamics, that have so severely limited PrEP uptake and persistence among women to date. Evidence from the contraceptive literature underscores the importance of method choice, with greater availability of options linked to increased contraceptive uptake, increased persistence, and better health outcomes [10]. The time is long overdue to assess on-demand regimens of oral PrEP for women.
In this issue of The Journal of Infectious Diseases, Engel and colleagues present modeled data in support of on-demand PrEP dosing for women from an established pharmacokinetic/pharmacodynamic tissue model of F/TDF for PrEP [11]. Using data from their published in vitro/in vivo model in which concentrations of the
|
|
| |
| |
|
|
|
