Single-nucleotide polymorphisms in ABC drug transporters alter expression and circulating tenofovir in healthy South African women exposed to pre-exposure prophylaxis

Pharmacogenomics. 2023 Jul;24(11):599-613. doi: 10.2217/pgs-2023-0058. Epub 2023 Jul 28.

Abstract

Aim: We investigated if single-nucleotide polymorphisms (SNPs) in ATP-binding cassette (ABC) drug transporters alter gene expression and tenofovir disposition in South African women taking Truvada® for HIV prevention. Materials & methods: In 393 women, real-time PCR was used to determine the associations between six SNPs in ABC transporter genes, mRNA expression and circulating-tenofovir. Results: Univariable and multivariable analyses showed that CT and TT relative to CC genotypes for the ABCC4(3463C/T) SNP had significantly higher tenofovir levels. In contrast, the AA genotype for the ABCC4(4976A/G) SNP showed significantly less tenofovir, while mRNA expression was increased. Conclusion: SNPs in the ABCC4 gene may differentially affect gene expression and circulating tenofovir. Their impact may inform on low pre-exposure prophylaxis efficacy and discern effective drugs in clinical trials of African women enriched for certain genotypes.

Keywords: ATP-binding cassette drug transporters; African women; HIV; South Africa; Truvada®; pre-exposure prophylaxis; single-nucleotide polymorphisms; tenofovir.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Anti-HIV Agents* / therapeutic use
  • Female
  • HIV Infections* / drug therapy
  • HIV Infections* / genetics
  • HIV Infections* / prevention & control
  • Humans
  • Polymorphism, Single Nucleotide / genetics
  • Pre-Exposure Prophylaxis*
  • RNA, Messenger
  • South Africa
  • Tenofovir / therapeutic use

Substances

  • Tenofovir
  • ATP-Binding Cassette Transporters
  • RNA, Messenger
  • Anti-HIV Agents