Drug transporter mRNA expression and genital inflammation in South African women on oral pre-exposure prophylaxis (PrEP)

This study investigated whether biological factors beyond pill‑taking habits might influence how well oral HIV prevention medicine (PrEP) works in South African women. The researchers focused on proteins called drug transporters that help move drugs in and out of cells and may affect how much of the active drug reaches the female genital tract, where HIV is often transmitted. They measured mRNA expression levels (a marker of how much transporter protein may be made) in both blood and genital tract samples from young women taking oral PrEP (TDF/FTC) over six months. They also measured inflammation in genital samples using a panel of cytokines and chemokines.

They found that the expression levels of several drug transporters in the genital tract were positively correlated with levels in blood after women had started PrEP, and one transporter (OAT‑1) was correlated even before drug use. This suggests some consistency in transporter expression between compartments.

When the women had signs of genital inflammation, one efflux transporter (MATE‑1) tended to be higher, while another (MRP‑4) tended to be lower compared with women without inflammation. There were also modest associations between certain inflammatory proteins and the expression of some drug transporters. However, there was no clear link between transporter expression and blood levels of the active PrEP drug.

Overall, the results indicate that genital inflammation may alter drug transporter expression, which in turn could influence how PrEP drugs distribute in the genital tract. This work helps explain why PrEP effectiveness can vary and highlights the need to consider biological factors, not just adherence, when evaluating PrEP performance in women.

Disclaimer: This lay summary was generated by AI and has not been approved by any of the authors yet.