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

Nomusa M Zondo; Parveen Sobia; Aida Sivro; Sinaye Ngcapu; Veron Ramsuran; Derseree Archary

doi:10.3389/fgene.2022.940661

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

Front Genet. 2022 Sep 29:13:940661. doi: 10.3389/fgene.2022.940661. eCollection 2022.

Authors

Nomusa M Zondo^{1

2}, Parveen Sobia^{1

2}, Aida Sivro^{1

2}, Sinaye Ngcapu^{1

2}, Veron Ramsuran^{1

2}, Derseree Archary^{1

2}

Affiliations

¹ Centre for the AIDS Programme of Research in South Africa (CAPRISA), Mucosal Immunology Department, Durban, South Africa.
² Department of Medical Microbiology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.

Abstract

The use of antiretrovirals (ARVs) as oral, topical, or long-acting pre-exposure prophylaxis (PrEP) has emerged as a promising strategy for HIV prevention. Clinical trials testing Truvada^® [tenofovir disoproxil fumarate (TDF)/tenofovir (TFV) and emtricitabine (FTC)] as oral or topical PrEP in African women showed mixed results in preventing HIV infections. Since oral and topical PrEP effectiveness is dependent on adequate drug delivery and availability to sites of HIV infection such as the blood and female genital tract (FGT); host biological factors such as drug transporters have been implicated as key regulators of PrEP. Drug transporter expression levels and function have been identified as critical determinants of PrEP efficacy by regulating PrEP pharmacokinetics across various cells and tissues of the blood, renal tissues, FGT mucosal tissues and other immune cells targeted by HIV. In addition, biological factors such as genetic polymorphisms and genital inflammation also influence drug transporter expression levels and functionality. In this review, drug transporters and biological factors modulating drug transporter disposition are used to explain discrepancies observed in PrEP clinical trials. This review also provides insight at a pharmacological level of how these factors further increase the susceptibility of the FGT to HIV infections, subsequently contributing to ineffective PrEP interventions in African women.

Keywords: African women; PrEP (pre-exposure prophylaxis); drug transporters; female genital tract (FGT); inflammation; single nucleotid polymorphism (SNP).

Publication types

Review