Pharmacology of Antiretrovirals in the Female Genital Tract for HIV Prevention

Overview

Journal J Clin Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2018 Jun 15

PMID 29901863

Citations 7

Authors

Melanie R Nicol

Joseph A Corbino

Mackenzie L Cottrell

Affiliations

Soon will be listed here.

Abstract

Preexposure prophylaxis (PrEP) is a powerful tool that, as part of a comprehensive prevention package, has potential to significantly impact the HIV epidemic. PrEP effectiveness is believed to be dependent on the exposure and efficacy of antiretrovirals at the site of HIV transmission. Clinical trial results as well as modeling and simulation indicate the threshold of adherence required for PrEP efficacy of emtricitabine/tenofovir disoproxil fumarate may differ between sites of HIV transmission with less forgiveness for missed doses in women exposed through genital tissue compared to people exposed through colorectal tissue. This suggests a role for local and host factors to influence mucosal pharmacology. Here we review the mucosal pharmacology of antiretrovirals in the female genital tract and explore potential determinants of PrEP efficacy. Host factors such as inflammation, coinfections, hormonal status, and the vaginal microbiome will be explored as well as the role of drug-metabolizing enzymes and transporters in regulating local drug exposure. The use of preclinical and early clinical models to predict clinical effectiveness is also discussed.

Citing Articles

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

Zondo N, Sobia P, Sivro A, Ngcapu S, Mahomed S, Mansoor L AIDS Res Ther. 2025; 22(1):18.

PMID: 39955595 PMC: 11829381. DOI: 10.1186/s12981-025-00713-z.

Lenacapavir: Playing the Long Game in the New Era of Antiretrovirals.

Neverette N, Dumond J, McMahon D, Devanathan A Clin Pharmacol Ther. 2024; 117(2):353-367.

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Pharmacogenomics of drug transporters for antiretroviral long-acting pre-exposure prophylaxis for HIV.

Zondo N, Sobia P, Sivro A, Ngcapu S, Ramsuran V, Archary D Front Genet. 2022; 13:940661.

PMID: 36246609 PMC: 9557974. DOI: 10.3389/fgene.2022.940661.

Validation and clinical application of a method to quantify efavirenz in cervicovaginal secretions from flocked swabs using liquid chromatography tandem mass spectrometry.

Olagunju A, Nwogu J, Eniayewu O, Atoyebi S, Amara A, Kpamor J Wellcome Open Res. 2022; 6:246.

PMID: 36034058 PMC: 9379332. DOI: 10.12688/wellcomeopenres.17202.3.

Genital Immune Cell Activation and Tenofovir Gel Efficacy: A Case-Control Study.

Liebenberg L, Passmore J, Osman F, Jewanraj J, Mtshali A, Garcia-Lerma J Clin Infect Dis. 2022; 75(6):1088-1091.

PMID: 35142337 PMC: 9989354. DOI: 10.1093/cid/ciac115.

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