Polymorphisms at CYP enzymes, NR1I2 and NR1I3 in association with virologic response to antiretroviral therapy in Brazilian HIV-positive individuals

Pharmacogenomics J. 2022 Feb;22(1):33-38. doi: 10.1038/s41397-021-00254-4. Epub 2021 Sep 9.

Abstract

Virologic failure of antiretroviral therapy (ART) may be explained by single nucleotide polymorphisms (SNPs) in drug absorption and metabolism genes. Here, we characterized the associations between polymorphisms in cytochrome P450 enzymes' genes CYP2B6 and CYP3A4/A5, nuclear receptor genes NR1I2/3, and initial ART efficacy among 203 HIV-positive individuals from Rio de Janeiro. Association between SNPs and virologic control was evaluated after 6 and 12 months of follow-up using Cox regression models. The SNP rs2307424 (NR1I3) was associated with increased virologic response after 12 months of treatment, while rs1523127 (NR1I2), rs3003596, and rs2502815 (NR1I3) were associated with decreased response. Increased virologic response after 12 months (adjHR = 1.54; p = 0.02) was also observed among carriers of the NR1I3 haplotype rs2502815G-rs3003596A-rs2307424A versus the reference haplotype G-A-G. Our results suggest that NR1I2 and NR1I3 variants are associated with virologic responses to ART among Brazilians.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Brazil
  • Cohort Studies
  • Constitutive Androstane Receptor / genetics*
  • Cytochrome P-450 CYP2D6 / genetics
  • Cytochrome P-450 CYP3A / genetics
  • Cytochrome P-450 Enzyme System / genetics*
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • HIV Infections / virology*
  • HIV Seropositivity / drug therapy*
  • HIV Seropositivity / genetics*
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Pregnane X Receptor / genetics*
  • Receptors, N-Methyl-D-Aspartate
  • Treatment Outcome

Substances

  • Anti-HIV Agents
  • Constitutive Androstane Receptor
  • NR1 NMDA receptor
  • NR1I2 protein, human
  • NR1I3 protein, human
  • Pregnane X Receptor
  • Receptors, N-Methyl-D-Aspartate
  • Cytochrome P-450 Enzyme System
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human