Impact of vaginal microbiome communities on HIV antiretroviral-based pre-exposure prophylaxis (PrEP) drug metabolism (PLoS Pathog 2020, 16(12):e1009024)

報告日期: 2021/03/23
報告時間: 16:10/17:00
報告學生: Paramita Liya
講評老師: 陳振暐
附件下載:

Impact of vaginal microbiome communities on HIV antiretroviral-based pre-exposure prophylaxis (PrEP) drug metabolism

Cheu R.K., et al. (2020). PLoS Pathog 16(12): e1009024.

https://doi.org/10.1371/journal.ppat.1009024

Speaker          : Liya Paramita (潘利亞)                Time      : 16.10 – 17.00

Commentator: Prof. Jenn-Wei Chen                     Room    : Collage of Medicine 601

Abstract:

There are 35 million people worldwide living with human immunodeficiency virus (HIV), which is half of them are women. With no efficacious vaccine, HIV prevention strategies are essential to avoid HIV transmission. However, oral PrEP with Tenofovir/Emtricitabine (TDF/FTC) has demonstrated efficacy in men who have sex with men (MSM) but not efficacious in women. Recent evidence demonstrated that vaginal microbial communities are associated with increased HIV acquisition risk and may impact PrEP efficacy. However, the role of these microbes in altering the pharmacokinetics of PrEP drugs is unknown. In this study, the author investigated how vaginal bacteria alter PrEP drug concentrations through drug metabolism. Tenofovir (TFV), tenofovir alafenamide (TAF), and dapivirine (DPV) were used for target cells and illustrate how drug metabolism changes relative to bacterial community compositions over time. The result shown that vaginal dysbiosis mediated drug metabolism. In the presence of Lactobacillus, target cells uptake the PrEP drugs TFV and DPV more effectively, while PrEP uptake decreased in non-Lactobacillus community. In addition, when compared to cultures with Lactobacillus, Gardnerella vaginalis culture cells developed significantly less intracellular active drug versus drug administered.The quantity of bacteria able to internalize and metabolize the drug relative to the quantity of bacteria unable to interact with the drug significantly dictates the amount of active drug formed. As a result, the effects of varying microbial populations had greater influences on active drug formation as the time from drug administration increased, suggesting time between doses could be even more important for patients with vaginal dysbiosis.

References

Anderson P.L., et al. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Science translational medicine. 2012;4(151):151ra25–ra25. pmid:22972843

Klatt N.R., et al. Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women. Science. 2017;356(6341):938–45. Epub 2017/06/03. pmid:28572388.